C3 glomerulopathy: A new complement-based entity

array:23 ["pii" => "S2254887414000344" "issn" => "22548874" "doi" => "10.1016/j.rceng.2014.01.009" "estado" => "S300" "fechaPublicacion" => "2014-06-01" "aid" => "908" "copyright" => "Elsevier España, S.L.. All rights reserved" "copyrightAnyo" => "2013" "documento" => "simple-article" "crossmark" => 0 "subdocumento" => "crp" "cita" => "Rev Clin Esp. 2014;214:266-74" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 992 "formatos" => array:2 [ "HTML" => 990 "PDF" => 2 ] ] "Traduccion" => array:1 [ "es" => array:19 [ "pii" => "S0014256514000228" "issn" => "00142565" "doi" => "10.1016/j.rce.2014.01.016" "estado" => "S300" "fechaPublicacion" => "2014-06-01" "aid" => "908" "copyright" => "Elsevier España, S.L." "documento" => "simple-article" "crossmark" => 0 "subdocumento" => "crp" "cita" => "Rev Clin Esp. 2014;214:266-74" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 4120 "formatos" => array:2 [ "HTML" => 3623 "PDF" => 497 ] ] "es" => array:13 [ "idiomaDefecto" => true "cabecera" => "Actualización clínica" "titulo" => "Glomerulopatía C3: una nueva entidad basada en el complemento" "tienePdf" => "es" "tieneTextoCompleto" => "es" "tieneResumen" => array:2 [ 0 => "es" 1 => "en" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "266" "paginaFinal" => "274" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "C3 glomerulopathy: A new complement-based entity" ] ] "contieneResumen" => array:2 [ "es" => true "en" => true ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figura 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1362 "Ancho" => 1652 "Tamanyo" => 93878 ] ] "descripcion" => array:1 [ "es" => "Vía alternativa del complemento. En la activación de la vía alternativa del complemento, C3 convertasa escinde C3 en C3a y C3b, siendo este último, a su vez, un potente amplificador y generador de C3 convertasa. Este proceso está regulado por factorH, que inhibe la C3 convertasa, y factorI, que convierte C3b en C3b inactivo, frenando así la cascada. Además, de los productos derivados de la acción de C3 convertasa se genera C5 convertasa. Esta enzima escinde C5 en C5a y C5b. La unión de C5b con C6-C9 forma el complejo de ataque a membrana (CAM) con actividad quimiotáctica en las superficies celulares, resultando en la lisis celular." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "A. de Lorenzo, S. Tallón, B. Hernández-Sevillano, G. de Arriba" "autores" => array:4 [ 0 => array:2 [ "nombre" => "A." "apellidos" => "de Lorenzo" ] 1 => array:2 [ "nombre" => "S." "apellidos" => "Tallón" ] 2 => array:2 [ "nombre" => "B." "apellidos" => "Hernández-Sevillano" ] 3 => array:2 [ "nombre" => "G." "apellidos" => "de Arriba" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2254887414000344" "doi" => "10.1016/j.rceng.2014.01.009" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2254887414000344?idApp=WRCEE" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0014256514000228?idApp=WRCEE" "url" => "/00142565/0000021400000005/v2_201406130025/S0014256514000228/v2_201406130025/es/main.assets" ] ] "itemAnterior" => array:19 [ "pii" => "S2254887413001471" "issn" => "22548874" "doi" => "10.1016/j.rceng.2013.12.003" "estado" => "S300" "fechaPublicacion" => "2014-06-01" "aid" => "861" "copyright" => "Elsevier España, S.L." "documento" => "simple-article" "crossmark" => 0 "subdocumento" => "crp" "cita" => "Rev Clin Esp. 2014;214:258-65" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 287 "HTML" => 287 ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "Clinical up-date" "titulo" => "Radiographic patterns in the diagnostic approach to organizing pneumonia" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "258" "paginaFinal" => "265" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Patrones radiológicos en la aproximación diagnóstica a la neumonía organizativa" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1051 "Ancho" => 1344 "Tamanyo" => 174719 ] ] "descripcion" => array:1 [ "en" => "Other radiological patterns. (A) Axial slice of chest computed tomography in which ill-defined nodular opacities of various sizes can be observed, which do not exceed 1 centimeter, with patchy distribution and no regional predominance. (B) Axial slice of chest computed tomography in which patchy consolidations with peripheral ground-glass attenuation can be observed, illustrating an example of the “halo sign” (white arrows). (C) Coronal reconstruction of chest CT in which a central area of ground-glass attenuation (star white) with a peripheral area of consolidation can be observed in the lower right lobe, forming an almost complete ring, suggesting an “inverted halo” or “atoll” sign (white arrows). (D) Axial slice of chest CT in which a cobblestone pattern can be seen, distributed through both lungs, predominantly in the lower lobes." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "C. Utrilla Contreras, M. Fernández-Velilla Peña, F. García Río, M.I. Torres Sánchez" "autores" => array:4 [ 0 => array:2 [ "nombre" => "C." "apellidos" => "Utrilla Contreras" ] 1 => array:2 [ "nombre" => "M." "apellidos" => "Fernández-Velilla Peña" ] 2 => array:2 [ "nombre" => "F." "apellidos" => "García Río" ] 3 => array:2 [ "nombre" => "M.I." "apellidos" => "Torres Sánchez" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S001425651300369X" "doi" => "10.1016/j.rce.2013.10.015" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S001425651300369X?idApp=WRCEE" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2254887413001471?idApp=WRCEE" "url" => "/22548874/0000021400000005/v1_201406010020/S2254887413001471/v1_201406010020/en/main.assets" ] "en" => array:20 [ "idiomaDefecto" => true "cabecera" => "Clinical up-date" "titulo" => "C3 glomerulopathy: A new complement-based entity" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "266" "paginaFinal" => "274" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "A. de Lorenzo, S. Tallón, B. Hernández-Sevillano, G. de Arriba" "autores" => array:4 [ 0 => array:4 [ "nombre" => "A." "apellidos" => "de Lorenzo" "email" => array:1 [ 0 => "doctorberto@hotmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "¿" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "S." "apellidos" => "Tallón" ] 2 => array:2 [ "nombre" => "B." "apellidos" => "Hernández-Sevillano" ] 3 => array:2 [ "nombre" => "G." "apellidos" => "de Arriba" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Nefrología, Hospital Universitario de Guadalajara, Departamento de Medicina, Universidad de Alcalá, Alcalá de Henares, Madrid, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Glomerulopatía C3: una nueva entidad basada en el complemento" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1362 "Ancho" => 1652 "Tamanyo" => 95391 ] ] "descripcion" => array:1 [ "en" => "Alternative complement pathway. In the activation of the alternative complement pathway, C3 convertase cleaves C3 into C3a and C3b, the latter of which is a potent C3 convertase amplifier and generator. This process is regulated by factor H (which inhibits C3 convertase) and factor I (which converts C3b into inactive C3b, thereby slowing the cascade). In addition, C5 convertase is generated from the products derived from the action of C3 convertase. This enzyme cleaves C5 into C5a and C5b. The binding of C5b with C6–C9 forms the membrane attack complex (MAC) with chemotactic activity in the cell surfaces, resulting in cell lysis." ] ] ] "textoCompleto" => "The clinical problemAdvances in the understanding of alternative complement pathway abnormalities have led to the recent discovery of a new entity in the setting of glomerular diseases. This entity is known as C3 glomerulopathy.<a class="elsevierStyleCrossRefs" href="#bib0005">1–4</a> The onset of this new disease makes the classification of membranoproliferative glomerulonephritis obsolete and opens a new field of research in the setting of its treatment using new biological therapies such as the anti-C5 monoclonal antibody eculizumab.C3 glomerulopathyThe term C3 glomerulopathy includes 2 subtypes: dense-deposit disease (DDD) and C3 glomerulonephritis (GNC3) itself, 2 entities that have in common the isolated deposit of complement 3 (C3) fraction, i.e., in the absence of immunoglobulins, and which, in turn, have ultrastructural differences that allow them to be differentiated.Alternative complement pathway abnormalities cause the isolated deposit of factor C3 in the mesangium and capillary wall, which is characteristic of membranoproliferative glomerulonephritis and is produced without concomitant immunoglobulin deposit.<a class="elsevierStyleCrossRefs" href="#bib0025">5,6</a> The clinical expression is a microscopic hematuria-proteinuria syndrome with a variable degree of proteinuria, which can reach the nephrotic range. If electron-dense deposits visible by electron microscope are identified, then the disease is classified as DDD. If these deposits are absent, the disease is classified as GNC3, in which case the deposits are very similar to those of glomerulonephritis mediated by immune complexes (located at the mesangial, subendothelial, subepithelial and/or intramembranous level), although without them being present.<a class="elsevierStyleCrossRef" href="#bib0035">7</a>Dense-deposit diseaseThis is an extremely rare disease (2–3 cases per million) that mainly affects children and young adults and is slightly more common in women (3:2 ratio). Clinically, the disease presents with varying amounts of proteinuria and hematuria. The essential characteristic that defines and differentiates this entity is the presence of electron-dense deposits in the glomerular basement membrane (GBM) and mesangium, and not the presence or absence of a membranoproliferative pattern observed under optical microscopy consisting of the thickening of the GBM along with the proliferation of mesangial cells (which is only present in 25% of affected individuals). The most common histological pattern is mesangial proliferation (45%). For this reason, we can say that the term membranoproliferative glomerulonephritis (MPGN) type II has become obsolete. In fact, MPGN is currently classified as mediated by immune complexes (which include types I and III, caused most often by the hepatitis B and C viruses whose antigenemia causes the depositing of immune complexes at the glomerular level)<a class="elsevierStyleCrossRefs" href="#bib0040">8–10</a> and by the complement (DDD and GNC3) (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). Given that there is a deregulation of the alternative complement pathway in the origin of DDD, 60–80% of cases have complement consumption data manifested by low serum levels of C3 and degradation products.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>To confirm a suspected diagnosis, a renal biopsy is essential. Here the diagnostic criterion is the presence of electron-dense deposits in the GBM, along with direct immunofluorescence for C3 and the absence of immunoglobulin deposits in most cases, as well as a reduction in plasma C3 levels, whose levels need to be determined. Once the diagnosis has been confirmed and depending on the availability at each center, a complement study should be requested.<a class="elsevierStyleCrossRef" href="#bib0055">11</a>Approximately 50% of affected individuals progress to end-stage renal disease (ESRD) at 10 years after diagnosis, although the course is more aggressive and rapid in young patients and women.<a class="elsevierStyleCrossRefs" href="#bib0060">12,13</a>C3 glomerulonephritisThe concept of GNC3 was coined in 2007 when Servais et al.<a class="elsevierStyleCrossRef" href="#bib0005">1</a> described what is known as “primary glomerulonephritis with isolated C3 deposits”. The fundamental requirement for the diagnosis of this entity, as with DDD, was the isolated deposits of C3 on immunofluorescence. It was noteworthy that these patients had none of the typical characteristics of DDD, and in fact the deposits resembled those of MPGN types I and III, with the significant exception that they lacked immune complexes. Reduced serum C3 levels appear less frequently than in DDD in 40% of cases. There are no major differences in terms of the clinical presentation between DDD and GNC3, although GNC3 has a slightly better prognosis; approximately 20% of patients progress to ESRD at 10 years, and 30% progress to stages 3–4 CKD.<a class="elsevierStyleCrossRef" href="#bib0005">1</a>EtiopathogenesisThe complement system is a mechanism mainly involved in defending against infections (mainly gram negative germs) and tumor cells. The system consists of approximately 30 factors that are mostly plasma proteins. Complement activation can be initiated by 3 different pathways (classical, alternative and lectin). It involves changes in particular components that result in chain reactions, in such a way that active products are generated that, in addition to ensuring that the chain continues to the next reaction, can have important biological activities in the body's defense. All these are due to the fact that most complement factors are proteolytic in nature.<a class="elsevierStyleCrossRef" href="#bib0070">14</a> The alternative complement pathway is generally active in circulation, although at low levels due to regulatory mechanisms that prevent self-harm.There are 2 main regulators of this pathway: factors H and I, whose abnormalities (either inherited or acquired) create an imbalance between activating and inhibiting factors (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). DDD and GNC3 have a common etiopathogenic origin in the mutations of the alternative complement pathway. A disorder in the regulation of C3 and C5 convertases generates an unbridled activation of the system and a considerable quantity of C3b and membrane attack complex (MAC), which ends by accumulating in the glomerular capillary wall, ultimately generating C3 glomerulopathy.<a class="elsevierStyleCrossRef" href="#bib0075">15</a> DDD and GNC3 can probably be differentiated by the degree to which one or the other convertase is affected. It seems that in the case of DDD, the predominant disorder is at the C3 convertase level, while the origin of GNC3 is mainly due to a C5 convertase disorder.<elsevierMultimedia ident="fig0005"></elsevierMultimedia>In recent years, there have been numerous publications on this disease. Several mutations of genes involved in this process of improper activation of the complement have been reported, such as CFHR5, factor H, factor I and factor C3,<a class="elsevierStyleCrossRefs" href="#bib0080">16–19</a> although the majority of patients have polymorphisms of several genes. These polymorphisms generate new epitopes that determine the development of autoantibodies known as C3 nephritic factor, which acts as a stabilizer of C3 convertase, preventing the action of physiological regulators such as factor H. Thus, for DDD, 60–80% of cases progress with complement consumption data manifested by low serum levels of C3 and products resulting from its degradation. In GNC3, the percentage of reduced C3 is somewhat lower, appearing in 40% of patients. Sethi et al.<a class="elsevierStyleCrossRef" href="#bib0100">20</a> reported on a series of 12 patients with GNC3 and alternative complement pathway disorder. Initially, 9 of the 12 patients with GNC3 were classified as having MPGN I (n=4), MPGN III (n=1) and postinfectious glomerulonephritis (n=4). The Sethi group showed that the proteomic profile of GNC3 was similar to that of DDD (with a predominance of C3 and final complement pathway components). This result supports the theory that the presence of isolated C3 is the main marker of alternative complement pathway dysfunction in C3 glomerulopathy, regardless of its optical or ultrastructural histology.The greatest contribution from the genotypic and phenotypic points of view has been the data from 2 recently published cohorts. The first, published in 2010 by Gale et al.<a class="elsevierStyleCrossRef" href="#bib0105">21</a> describes 91 patients belonging to 16 families of Cypriot origin with a CFHR5 mutation that encodes protein 5 related to factor H. The mutation was more common in men than in women (80% vs. 21%). In this case, the condition was labeled nephropathy CFHR5, characterized by persistent microscopic hematuria with gross hematuria coinciding with intercurrent upper respiratory infection (imitating the typical presentation of nephropathy by IgA deposits), as well as proteinuria in 38% of the cases, with progression to ESRD more likely in these cases, especially for males (78% vs. 22%).<a class="elsevierStyleCrossRef" href="#bib0110">22</a>In 2012, Servais et al.<a class="elsevierStyleCrossRef" href="#bib0115">23</a> studied a French cohort of 85 patients with C3 glomerulopathy, 56 of them with GNC3 and 29 with DDD. Sixty percent of the patients had microscopic hematuria; the proteinuria levels were slightly lower in the cases with GNC3 than in those with DDD (3.6±3.3g vs. 5.6±4.5g). Although both conditions are present in the young population, the patients with GNC3 were older (30.3±19.3 vs. 18.9±17.7 years). These authors were also the first to shed light on the possible etiological origin of GNC3, given that 31% of their patients had a mutation in factor H, factor I or in the membrane cofactor protein. They also observed that C3 nephritic factor was less common in GNC3 than in DDD (45% vs. 86%), which also occurred with reduced serum C3 levels (86.4% vs. 45.3%).Habbig et al.<a class="elsevierStyleCrossRef" href="#bib0120">24</a> reported on a family with 2 siblings of consanguineous parents with hematuria and proteinuria since childhood. Both siblings had reduced levels of serum C3 and complement regulatory factor B. A mesangial deposit of C3 and C5b-9 was observed in the biopsy, and numerous mesangial, intramembranous and subendothelial deposits were observed under electron microscopy. Genetic screening for factor H mutations showed that both children were homozygous for a lysine deletion. This deletion leads to a critical reduction of this cofactor inhibitor. Additionally, both patients and their healthy mother were positive for C3 nephritic factor. In 2010, Martínez-Barricarte et al.<a class="elsevierStyleCrossRef" href="#bib0125">25</a> published a report on a family with DDD and a C3 mutation. This mutation conferred resistance to C3 against its excision by C3 convertase, thereby preventing the formation of activated C3b. The disease in this family was caused exclusively by dysregulation in the fluid phase of the alternative pathway with no contribution from the terminal complement cascade (TCC). In contrast, the GNC3 described in the Cypriot families by Gale et al.<a class="elsevierStyleCrossRef" href="#bib0105">21</a> and in the siblings by Habbig et al. were associated with the C5 convertase disorder and the subsequent activation of the TCC (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>The alternative complement pathway disorder could also be due to acquired causes that trigger the formation of 2 types of antibodies (Ab), various inhibitors (antifactor H Ab and antifactor I Ab) and others that directly stimulate complement activation such as C3 nephritic factor, an IgG autoantibody that stabilizes C3 convertase, extending its half-life and enzymatic activity.Assessment of patients with C3 glomerulopathyIn the clinical assessment of patients with C3 glomerulopathy, the identification of the underlying defect in the alternative complement pathway can be very useful. It allows a family study to be carried out and prevents damage in relatives with subclinical involvement. Experts recommend measuring serum levels of CH50, C3, C3d, C4, factor H and factor I, studying their mutations, assessing the presence of autoantibodies such as C3 nephritic factor and conducting functional trials of the alternative complement pathway (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>).<a class="elsevierStyleCrossRefs" href="#bib0100">20,26,27</a><elsevierMultimedia ident="fig0010"></elsevierMultimedia>TreatmentDespite significant progress in the understanding of the underlying mechanisms, advances in treatment have not enabled the development of effective compounds. Various treatment modalities are used with varying degrees of effectiveness. Examples of treatments include renin–angiotensin axis blockade, plasmapheresis with plasma infusion and cellular immunosuppressants. The exception to this rule is biological therapy directed using the anti-C5 monoclonal antibody eculizumab.Renin–angiotensin axis inhibitorsThe current evidence on chronic kidney disease and glomerulopathy with nonselective proteinuria, as well as the data obtained by Servais et al.<a class="elsevierStyleCrossRef" href="#bib0115">23</a> in this group of diseases, support the use of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor antagonists (ARA II) to preserve renal function in this group of diseases.<a class="elsevierStyleCrossRefs" href="#bib0140">28,29</a>Plasma therapyExperience with its use is based on individual cases, such as the report by Lich et al.<a class="elsevierStyleCrossRef" href="#bib0090">18</a> of 2 twins diagnosed with DDD and the previously mentioned report by Habbig et al.<a class="elsevierStyleCrossRef" href="#bib0120">24</a> Both cases had factor H deficiency secondary to a mutation and a satisfactory response to factor H repletion achieved using plasma exchange. The direct contribution of this factor could be available for therapeutic use in the near future.<a class="elsevierStyleCrossRef" href="#bib0150">30</a> In other cases, plasmapheresis with replenishment of plasma factors has not been effective, according to the reports by McCaughan et al.<a class="elsevierStyleCrossRef" href="#bib0155">31</a> and Martinez-Barricarte et al.,<a class="elsevierStyleCrossRef" href="#bib0125">25</a> all of which dealt with DDD. Martinez-Barricarte et al. postulated the presence of a C3 convertase mutation that would make it resistant to the inhibitory action of factorH and would therefore hinder the effectiveness of replenishing plasma factor. This would in turn require new specific treatments aimed at restoring control of C3 convertase activity and eliminating C3 degradation products from plasma.<a class="elsevierStyleCrossRef" href="#bib0100">20</a>Cellular immunosuppressionThere is no evidence supporting the use of immunosuppressive therapy in C3 glomerulopathy,<a class="elsevierStyleCrossRef" href="#bib0015">3</a> given that the various lines of treatment have provided highly variable responses and questionable efficacy, as is the case with prednisone and mycophenolate, which have shown no benefit according to the cases reported by Sethi et al.<a class="elsevierStyleCrossRef" href="#bib0100">20</a> and Bomback et al.<a class="elsevierStyleCrossRef" href="#bib0160">32</a> The combination of these agents with biological therapies, such as the antilymphocyte CD20 monoclonal antibody rituximab used by McCaughan et al.,<a class="elsevierStyleCrossRef" href="#bib0155">31</a> was also ineffective in a kidney transplant recipient.EculizumabEculizumab is an anti-C5 antibody that impedes the excision of C5 in C5b and decreases the production of C5a, thereby preventing the activation of the terminal cascade and the formation of CAM (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>).<a class="elsevierStyleCrossRef" href="#bib0035">7</a> Eculizumab was the first drug that, using this mechanism of action, managed to effectively and safely reduce hemolysis in paroxysmal nocturnal hemoglobinuria. This condition was the first indication for eculizumab in 2008,<a class="elsevierStyleCrossRef" href="#bib0165">33</a> although practically every year new applications and therapeutic indications are being discovered for numerous diseases mediated by the complement, such as atypical hemolytic-uremic syndrome,<a class="elsevierStyleCrossRef" href="#bib0170">34</a> C3 glomerulopathy and HELLP syndrome.<a class="elsevierStyleCrossRef" href="#bib0175">35</a> The most important secondary effect of eculizumab is a direct consequence of the inhibition of the terminal complement cascade, which predisposes patients to infections by encapsulated germs such as Neisseria meningitidis. Vaccinations and antibiotic prophylaxis are therefore recommended at least 14days before starting treatment with eculizumab.<a class="elsevierStyleCrossRefs" href="#bib0180">36,37</a><elsevierMultimedia ident="tbl0015"></elsevierMultimedia>The first published cases of glomerulonephritis treated with eculizumab<a class="elsevierStyleCrossRefs" href="#bib0155">31,32,38–41</a> appeared in the literature in 2012, 6 of them with DDD, 3 with GNC3 and another diagnosed with MPGN I refractory to treatment. Of the 10 patients who underwent the treatment, improved renal function parameters were observed in 8, with 1 patient showing lower glomerulonephritis activity at the histopathological level in a second biopsy. The 2 remaining patients experienced renal function deterioration during the follow-up, 1 of whom eventually required dialysis. It is worth noting that 2 of the patients who responded positively worsened immediately after the use of eculizumab was withdrawn. An association was found between MAC levels prior to treatment and the response to the same; these levels could therefore be useful as a predictive factor.Given the high cost of therapy with this antibody, patient candidates for undergoing this therapy should be selected carefully. A recent review by Zuber et al.<a class="elsevierStyleCrossRef" href="#bib0210">42</a> on the use of eculizumab in atypical hemolytic-uremic syndrome and C3 glomerulopathy suggested that optimal candidates for taking eculizumab would be patients with a recent diagnosis, active inflammatory lesions (crescent formation and endocapillary proliferation) and minimal interstitial fibrosis in the pathology, as well as an increase in serum creatinine and/or proteinuria levels and high serum MAC levels (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>).<a class="elsevierStyleCrossRefs" href="#bib0160">32,43</a><elsevierMultimedia ident="fig0015"></elsevierMultimedia>PrognosisThe accumulated experience indicates that the long-term prognosis is poor, given that a high percentage of patients progress to ESRD (approximately 50% of patients with DDD and 15–20% with GNC3 at 10 years), which might be due to the lesser aggressiveness of GNC3.<a class="elsevierStyleCrossRefs" href="#bib0005">1,19–24,31,32,38,39,41,44–46</a> A possible explanation is the increased prevalence of C3 nephritic factor in DDD (80% vs. 45–50% in GNC3). It is clear that more studies and case series are needed to assess the long-term prognosis of this new entity.Conclusions and recommendationsC3 glomerulopathy is a rare condition with an unfortunate renal prognosis, whose diagnosis is based on the finding of isolated C3 deposits in the renal biopsy. The detection of low plasma levels of complement regulation factors can provide a criterion for selecting the optimal treatment. The rarity of the disease has precluded the availability of strong evidence, and there are only small series of patients in whom different treatment modalities have been employed. Anticomplement therapy with eculizumab has offered the most promising results so far, although it requires a careful selection of candidates, such as those without no chronicity data in the renal biopsy and with renal function impairment and/or proteinuria, as well as high levels of MAC (when their measurement is possible), because they are associated with a better treatment response.In the case of our patient, electron microscopy of the renal biopsy confirmed the diagnosis of C3 glomerulonephritis. A study was performed of the alternative complement pathway, which showed normal levels of factors I and H, with no abnormal bands in the structural characterization of factor H and the absence of antifactor H antibodies and C3 nephritic factor. The genetic study, however, detected a change in heterozygosity in exon 4 of the factor I gene. Based on the test results predicting the functional effects, this change was proposed as benign, although complete functional studies are needed to rule out its association with this disease. Based on these results and confirming that the patient did not meet (at the time of the diagnosis) the recommended requirements for taking eculizumab, treatment was started with an angiotensin-converting enzyme inhibitor at the maximum tolerated dosage, reducing proteinuria by approximately 40% from its maximum value of 6g/day and maintaining normal renal function until now. In the event of renal function deterioration and/or increase in proteinuria despite renin–angiotensin–aldosterone system blockade, the experts recommended starting treatment with eculizumab or immunosuppressive therapy with mycophenolate mofetil if eculizumab is not available or if the patient does not clearly meet the criteria for eculizumab.Conflicts of interestThe authors declare that they have no conflicts of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:14 [ 0 => array:2 [ "identificador" => "xres343298" "titulo" => "Abstract" ] 1 => array:2 [ "identificador" => "xpalclavsec324878" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "xres343297" "titulo" => "Resumen" ] 3 => array:2 [ "identificador" => "xpalclavsec324877" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "The clinical problem" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "C3 glomerulopathy" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Dense-deposit disease" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "C3 glomerulonephritis" ] ] ] 6 => array:2 [ "identificador" => "sec0025" "titulo" => "Etiopathogenesis" ] 7 => array:2 [ "identificador" => "sec0030" "titulo" => "Assessment of patients with C3 glomerulopathy" ] 8 => array:3 [ "identificador" => "sec0035" "titulo" => "Treatment" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0040" "titulo" => "Renin–angiotensin axis inhibitors" ] 1 => array:2 [ "identificador" => "sec0045" "titulo" => "Plasma therapy" ] 2 => array:2 [ "identificador" => "sec0050" "titulo" => "Cellular immunosuppression" ] ] ] 9 => array:2 [ "identificador" => "sec0055" "titulo" => "Eculizumab" ] 10 => array:2 [ "identificador" => "sec0060" "titulo" => "Prognosis" ] 11 => array:2 [ "identificador" => "sec0065" "titulo" => "Conclusions and recommendations" ] 12 => array:2 [ "identificador" => "sec0070" "titulo" => "Conflicts of interest" ] 13 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2013-06-24" "fechaAceptado" => "2014-01-20" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec324878" "palabras" => array:7 [ 0 => "C3 glomerulopathy" 1 => "Dense-deposit disease" 2 => "Alternative complement pathway" 3 => "Factor H" 4 => "Factor I" 5 => "C3 nephritic factor" 6 => "Eculizumab" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec324877" "palabras" => array:7 [ 0 => "Glomerulopatía C3" 1 => "Enfermedad por depósitos densos" 2 => "Vía alternativa del complemento" 3 => "Factor H" 4 => "Factor I" 5 => "Factor nefrítico C3" 6 => "Eculizumab" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "C3 glomerulopathy is a new, recently described entity that has changed the perspective, treatment and classification of a number of glomerular diseases. It encompasses 2 similar but clearly differentiated pathologies—the dense-deposit disease and C3 glomerulonephritis itself. The alternative complement pathway plays a fundamental role in its pathogenesis and, specifically, the mutations and defects in its regulatory factors (mainly factor H and factor I), as well as the presence of acquired autoantibodies (C3 nephritic factor), which generates an unbridled activation of the system, and ultimately, a deposit of its products at the glomerular level. Its poor prognosis and onset in young populations make the detailed study of new therapeutic alternatives for this disease essential. Recently eculizumab, an anti-C5 antibody, has demonstrated effectiveness in the treatment of these patients." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "La glomerulopatía C3 es una nueva entidad descrita recientemente que ha cambiado la visión, el tratamiento y la clasificación de algunas enfermedades glomerulares. Engloba 2 patologías similares pero claramente diferenciadas: la enfermedad por depósitos densos y la glomerulonefritis C3 propiamente dicha. La vía alternativa del complemento juega un papel fundamental en su patogenia, y en concreto las mutaciones o defectos en sus factores reguladores (fundamentalmente factor H y factor I), así como la presencia de autoanticuerpos adquiridos (factor nefrítico C3) que generan una activación desenfrenada del sistema, y en último término un depósito de sus productos a nivel glomerular. Su mal pronóstico y la aparición en población joven hacen preciso el estudio de nuevas alternativas terapéuticas. Recientemente eculizumab, un anticuerpo anti C5, ha demostrado efectividad en el tratamiento de estos pacientes." ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: de Lorenzo A, Tallón S, Hernández-Sevillano B, de Arriba G. Glomerulopatía C3: una nueva entidad basada en el complemento. Rev Clin Esp. 2014;214:266–274." ] ] "multimedia" => array:6 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1362 "Ancho" => 1652 "Tamanyo" => 95391 ] ] "descripcion" => array:1 [ "en" => "Alternative complement pathway. In the activation of the alternative complement pathway, C3 convertase cleaves C3 into C3a and C3b, the latter of which is a potent C3 convertase amplifier and generator. This process is regulated by factor H (which inhibits C3 convertase) and factor I (which converts C3b into inactive C3b, thereby slowing the cascade). In addition, C5 convertase is generated from the products derived from the action of C3 convertase. This enzyme cleaves C5 into C5a and C5b. The binding of C5b with C6–C9 forms the membrane attack complex (MAC) with chemotactic activity in the cell surfaces, resulting in cell lysis." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 2145 "Ancho" => 2647 "Tamanyo" => 318630 ] ] "descripcion" => array:1 [ "en" => "Classification of membranoproliferative glomerulonephritis. Abbreviations: DDD, dense-deposit disease; GNC3, C3 glomerulonephritis; MPGN, membranoproliferative glomerulonephritis; IF, immunofluorescence; electron M., electron microscope; and GBM, glomerular basement membrane." ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1041 "Ancho" => 1649 "Tamanyo" => 109505 ] ] "descripcion" => array:1 [ "en" => "Treatment. Treatment regimen based on the findings of the complement functionality and genetics study. Abbreviations: ARA II, angiotensin II receptor antagonists; and ACEI, angiotensin-converting enzyme inhibitors." ] ] 3 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "Membranoproliferative glomerulonephritis mediated by immune complexes is produced by persistent antigenemia whose resulting immune complex activates the classical complement pathway. Direct immunofluorescence stainings will be positive to immunoglobulins, mainly IgG and IgM, as well as C3 and/or C1. C3 glomerulopathy is produced by dysfunction of the alternative complement pathway (mutations or autoantibodies); its direct immunofluorescence is negative for immunoglobulins but positive for complement (C3)." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mediated by immune complexes \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Infections \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Autoimmune diseases \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Neoplasms \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Gammopathies/dysproteinemias \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mediated by complement: C3 glomerulopathy \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Dense-deposit disease \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">C3 glomerulonephritis \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab509738.png" ] ] ] ] "descripcion" => array:1 [ "en" => "New classification of membranoproliferative glomerulonephritis." ] ] 4 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:3 [ "leyenda" => "Alb, plasma albumin; CFM, cyclophosphamide; Cr, plasma creatinine; E, steroids; DDD, dense-deposit disease; ESRD, end-stage renal disease; RF, renal function; Glom.C3, glomerulopathy C3; GNC3, glomerulonephritis C3; RAASI, renin–angiotensin–aldosterone system inhibitors; MMF, mycophenolate mofetil; N, native kidney; ND, not described; MCP, membrane cofactor protein; Pr, proteinuria; and T, kidney transplant." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Author \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">n \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Diagnosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Mutation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">C3 nephritic factor \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Native kidney/transplant \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Treatment \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Response/evolution \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Servais et al. (2007)<a class="elsevierStyleCrossRef" href="#bib0005">1</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">19 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">GNC3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Factor H (n=3)Factor I (n=2)MCP (n=1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Positive (n=7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">N \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">RAASI (n=8)E (n=5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">RF impairment (n=15), of these ESRDs (n=5) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Habbig et al. (2009)<a class="elsevierStyleCrossRef" href="#bib0120">24</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">GNC3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Factor H (n=2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Positive \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">N \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Fresh plasma infusion \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No disease progression \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Martínez-Barricarte et al. (2010)<a class="elsevierStyleCrossRef" href="#bib0095">19</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DDD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">C3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Negative \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">N (n=2)T (n=1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ND \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ND \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Darouich et al. (2011)<a class="elsevierStyleCrossRef" href="#bib0220">44</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">GNC3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ND \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ND \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">N \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ND \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ND \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Gale et al. (2010)<a class="elsevierStyleCrossRef" href="#bib0105">21</a>Athanasiou et al. (2011)<a class="elsevierStyleCrossRef" href="#bib0110">22</a>Deltas et al. (2013)<a class="elsevierStyleCrossRef" href="#bib0225">45</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">136 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Glom.C3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Factor H (CFHR5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Negative (n=4)<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">N \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ND \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">RF deterioration to ESRD (n=28) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Sugimoto et al. (2012)<a class="elsevierStyleCrossRef" href="#bib0230">46</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">GNC3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Factor H \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Negative \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">N \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">RAASI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No RF impairment Increased Pr \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Sethi et al. (2012)<a class="elsevierStyleCrossRef" href="#bib0100">20</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">GNC3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Factor H (n=2)Factor I (n=1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Positive (n=5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">N (n=10)T (n=2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">RAASI (n=2)RAASI+E (n=7)MMF (n=3)E+CFM (n=1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No RF impairment (n=10). No response (n=2) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Servais et al. (2012)<a class="elsevierStyleCrossRef" href="#bib0115">23</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">85 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">GNC3 (n=56) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Factor H (n=7)Factor I (n=3)MCP (n=1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Positive (n=24) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">N and T (number not specified) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">RAASI (n=19)IS (n=19) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">RF deterioration to ESRD (n=27) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DDD (n=29)<a class="elsevierStyleCrossRef" href="#tblfn0010">b</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Factor H (n=5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Positive (n=19) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">RAASI (n=14)IS (n=14) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">RF deterioration to ESRD (n=23) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">McCaughan et al. (2012)<a class="elsevierStyleCrossRef" href="#bib0155">31</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DDD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Positive \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">T \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Eculizumab \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Reduction of Cr and Pr \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Bomback et al. (2012)<a class="elsevierStyleCrossRef" href="#bib0160">32</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">GNC3 (n=3)DDD (n=3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Factor H (n=1)MCP (n=1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Positive (n=3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">N (n=3)T (n=3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Eculizumab \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Reduction of Cr (n=2) and Pr (n=1). Increase of Alb (n=1) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Vivarelli et al. (2012)<a class="elsevierStyleCrossRef" href="#bib0190">38</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DDD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Positive \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">N \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Eculizumab \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Reduction of Pr Increase of Alb \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Daina et al. (2012)<a class="elsevierStyleCrossRef" href="#bib0195">39</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DDD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Positive \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">N \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Eculizumab \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Reduction of Cr and Pr Increase of Alb \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Gurkan et al. (2013)<a class="elsevierStyleCrossRef" href="#bib0205">41</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">GNC3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Positive \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">T \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Eculizumab \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Stable Cr and Pr Histopathologic progression \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab509737.png" ] ] ] "notaPie" => array:2 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "Measurement performed in 4 patients." ] 1 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "b" "nota" => "The total number of patients in the series is complete with 41 patients who were diagnosed with type I membranoproliferative glomerulonephritis." ] ] ] "descripcion" => array:1 [ "en" => "Case series of C3 glomerulopathy: characteristics, treatment and evolution." ] ] 5 => array:7 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:3 [ "leyenda" => "Standard dosage for patients older than 18 years: 900mg weekly for the first 4 weeks, followed by 1200mg on the fifth week and subsequent maintenance with 1200mg every 2 weeks." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Weight \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Induction \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Administration<a class="elsevierStyleCrossRef" href="#tblfn0015">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Maintenance \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Administration<a class="elsevierStyleCrossRef" href="#tblfn0015">a</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">>40kg \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">900mg/week; 4dose \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">180mL in 30–45min \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1200mg every 2weeks \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">240mL in 30–45min \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">30–40kg \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">600mg/week; 2dose \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">120mL in 30–45min \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">900mg every 2weeks \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">180mL in 30–45min \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">20–30kg \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">600mg/week; 2dose \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">120mL in 30–45min \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">600mg every 2weeks \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">120mL in 30–45min \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10–20kg \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">600mg single dose \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">120mL in 30–45min \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">300mg every 2weeks \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">60mL in 30–45min \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5–10kg \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">300mg single dose \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">60mL in 30–45min \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">300mg every 2weeks \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">60mL in 30–45min \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab509739.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0015" "etiqueta" => "a" "nota" => "300mg vials (30mL) in dilution 5mg/mL with physiological saline (0.9%, 0.45%) or glucose solution (5%)." ] ] ] "descripcion" => array:1 [ "en" => "Eculizumab: dosage and method of administration." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:46 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Primary glomerulonephritis with isolated C3 deposits: a new entity which shares common genetic risk factors with haemolytic uraemic syndrome" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Servais" 1 => "V. Fremeaux-Bacchi" 2 => "M. Lequintrec" 3 => "R. Salomon" 4 => "J. Blouin" 5 => "J. Knebelmann" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/jmg.2006.045328" "Revista" => array:6 [ "tituloSerie" => "J Med Genet" "fecha" => "2007" "volumen" => "44" "paginaInicial" => "193" "paginaFinal" => "199" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17018561" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "C3 glomerulopathy: a new classification" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "F. Fakhouri" 1 => "V. Fremeaux-Bacchi" 2 => "L-H. Noel" 3 => "H.T. Cook" 4 => "M.C. Pickering" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/nrneph.2010.85" "Revista" => array:6 [ "tituloSerie" => "Nat Rev Nephrol" "fecha" => "2010" "volumen" => "6" "paginaInicial" => "494" "paginaFinal" => "499" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20606628" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Membranoproliferative glomerulonephritis type II (dense deposit disease): an update" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "G.B. Appel" 1 => "H.T. Cook" 2 => "G. Hageman" 3 => "J.C. Jennette" 4 => "M. Kashgarian" 5 => "M. Kirschfink" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1681/ASN.2005010078" "Revista" => array:6 [ "tituloSerie" => "J Am Soc Nephrol" "fecha" => "2005" "volumen" => "16" "paginaInicial" => "1392" "paginaFinal" => "1403" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15800116" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The amplification loop of the complement pathways" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "P.J. Lachmann" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0065-2776(08)04004-2" "Revista" => array:6 [ "tituloSerie" => "Adv Immunol" "fecha" => "2009" "volumen" => "104" "paginaInicial" => "115" "paginaFinal" => "149" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20457117" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Dense deposit disease: clinicopathologic study of 32 pediatric and adult patients" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S.H. Nasr" 1 => "A.M. Valeri" 2 => "G.B. Appel" 3 => "J. Sherwinter" 4 => "M.B. Stokes" 5 => "S.M. Said" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2215/CJN.03480708" "Revista" => array:6 [ "tituloSerie" => "Clin J Am Soc Nephrol" "fecha" => "2009" "volumen" => "4" "paginaInicial" => "22" "paginaFinal" => "32" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18971369" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0030" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Dense Deposit Disease Focus Group: new approaches to the treatment of dense deposit disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R.J.H. Smith" 1 => "J. Alexander" 2 => "P.N. Barlow" 3 => "M. Botto" 4 => "T.L. Cassavant" 5 => "H.T. Cook" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1681/ASN.2007030356" "Revista" => array:6 [ "tituloSerie" => "J Am Soc Nephrol" "fecha" => "2007" "volumen" => "18" "paginaInicial" => "2447" "paginaFinal" => "2456" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17675665" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0035" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Proliferative glomerulonephritis secondary to dysfunction of the alternative pathway of complement" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. Sethi" 1 => "F.C. Fervenza" 2 => "Y. Zhang" 3 => "S.H. Nasr" 4 => "N. Leung" 5 => "J. Vrana" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "J Am Soc Nephrol" "fecha" => "2011" "volumen" => "6" "paginaInicial" => "1009" "paginaFinal" => "1017" ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0040" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cryoglobulinemia and renal disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "C.E. Alpers" 1 => "K.D. Smith" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/MNH.0b013e3282f8afe2" "Revista" => array:6 [ "tituloSerie" => "Curr Opin Nephrol Hypertens" "fecha" => "2008" "volumen" => "17" "paginaInicial" => "243" "paginaFinal" => "249" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18408474" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0045" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The role of complement in cryoglobulin-induced immune complex glomerulonephritis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Trendelenburg" 1 => "L. Fossati-Jimack" 2 => "J. Cortes-Hernandez" 3 => "D. Turnberg" 4 => "M. Lewis" 5 => "S. Izui" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Immunol" "fecha" => "2005" "volumen" => "175" "paginaInicial" => "6909" "paginaFinal" => "6914" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16272350" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0050" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hepatitis C virus infection and membranoproliferative glomerulonephritis in Japan" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "H. Yamabe" 1 => "R.J. Johnson" 2 => "D.R. Gretch" 3 => "K. Fukushi" 4 => "H. Osawa" 5 => "M. Miyata" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Am Soc Nephrol" "fecha" => "1995" "volumen" => "6" "paginaInicial" => "220" "paginaFinal" => "223" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7579088" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0055" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "New approaches to the treatment of dense deposit disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R.J.H. Smith" 1 => "J. Alexander" 2 => "P.N. Barlow" 3 => "M. Botto" 4 => "T.L. Cassavant" 5 => "H.T. Cook" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1681/ASN.2007030356" "Revista" => array:6 [ "tituloSerie" => "J Am Soc Nephrol" "fecha" => "2007" "volumen" => "18" "paginaInicial" => "2447" "paginaFinal" => "2456" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17675665" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0060" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Idiopathic mesangiocapillary glomerulonephritis: comparison of types I and II in children and adults and long-term prognosis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.S. Cameron" 1 => "D.R. Turner" 2 => "J. Heaton" 3 => "D.G. Williams" 4 => "C.S. Ogg" 5 => "C. Chantler" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Am J Med" "fecha" => "1983" "volumen" => "74" "paginaInicial" => "175" "paginaFinal" => "192" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/6337487" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0065" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Idiopathic membranoproliferative glomerulonephritis in childhood" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "C.D. West" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Pediatr Nephrol" "fecha" => "1992" "volumen" => "6" "paginaInicial" => "96" "paginaFinal" => "103" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1536750" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0070" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The complement system in regulation of adaptive immunity" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "M.C. Carroll" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/ni1113" "Revista" => array:6 [ "tituloSerie" => "Nat Immunol" "fecha" => "2004" "volumen" => "5" "paginaInicial" => "981" "paginaFinal" => "986" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15454921" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0075" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "C3 glomerulopathy masquerading as acute postinfectious glomerulonephritis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "G. Sandhu" 1 => "A. Bansal" 2 => "A. Ranade" 3 => "J. Jones" 4 => "S. Cortell" 5 => "G.S. Markowitz" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1053/j.ajkd.2012.04.032" "Revista" => array:6 [ "tituloSerie" => "Am J Kidney Dis" "fecha" => "2012" "volumen" => "60" "paginaInicial" => "1039" "paginaFinal" => "1043" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22770945" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0080" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "H deficiency in two brothers with atypical dense intramembranous deposit disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Levy" 1 => "L. Halbwachs-Mecarelli" 2 => "M-C. Gubler" 3 => "G. Kohout" 4 => "A. Bensenouci" 5 => "P. Niaudet" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Kidney Int" "fecha" => "1986" "volumen" => "30" "paginaInicial" => "949" "paginaFinal" => "956" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2950269" "web" => "Medline" ] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0085" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Heterozygous and homozygous factor H deficiencies associated with hemolytic uremic syndrome or membranoproliferative glomerulonephritis: report and genetic analysis of 16 cases" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.A. Dragon-Durey" 1 => "V. Fremeaux-Bacchi" 2 => "C. Loirat" 3 => "J. Blouin" 4 => "P. Niaudet" 5 => "G. Deschenes" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Am Soc Nephrol" "fecha" => "2004" "volumen" => "15" "paginaInicial" => "787" "paginaFinal" => "795" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14978182" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0090" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Deletion of Lys224 in regulatory domain 4 of factor H reveals a novel pathomechanism for dense deposit disease (MPGN II)" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C. Licht" 1 => "S. Heinen" 2 => "M. Jozsi" 3 => "I. Löschmann" 4 => "R.E. Saunders" 5 => "S.J. Perkins" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/sj.ki.5000269" "Revista" => array:6 [ "tituloSerie" => "Kidney Int" "fecha" => "2006" "volumen" => "70" "paginaInicial" => "42" "paginaFinal" => "50" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16612335" "web" => "Medline" ] ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0095" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Human C3 mutation reveals a mechanism of dense deposit disease pathogenesis and provides insights into complement activation and regulation" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R. Martinez-Barricarte" 1 => "M. Heurich" 2 => "F. Valdes-Canedo" 3 => "E. Vazquez-Martul" 4 => "E. Torreira" 5 => "T. Montes" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1172/JCI43343" "Revista" => array:6 [ "tituloSerie" => "J Clin Invest" "fecha" => "2010" "volumen" => "120" "paginaInicial" => "3702" "paginaFinal" => "3712" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20852386" "web" => "Medline" ] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0100" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "C3 glomerulonephritis: clinicopathologic findings, complement abnormalities, glomerular proteomic profile, treatment and followup" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. Sethi" 1 => "F.C. Fervenza" 2 => "Y. Zhang" 3 => "L. Zand" 4 => "J.A. Vrana" 5 => "S.H. Nasr" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/ki.2012.212" "Revista" => array:6 [ "tituloSerie" => "Kidney Int" "fecha" => "2012" "volumen" => "82" "paginaInicial" => "465" "paginaFinal" => "473" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22673887" "web" => "Medline" ] ] ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0105" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Complement factor H-related protein 5 (CFHR5) nephropathy: an endemic cause of renal disease in Cyprus" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D.P. Gale" 1 => "E.G. de Jorge" 2 => "H.T. Cook" 3 => "R. Martinez-Barricarte" 4 => "A. Hadjisavvas" 5 => "G. Adam" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(10)60670-8" "Revista" => array:7 [ "tituloSerie" => "Lancet" "fecha" => "2010" "volumen" => "376" "paginaInicial" => "794" "paginaFinal" => "801" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20800271" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S000293780200087X" "estado" => "S300" "issn" => "00029378" ] ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0110" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Familial C3 glomerulopathy associated with CFHR5 mutations: Clinical characteristics of 91 patients in 16 pedigrees" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "Y. Athanasiou" 1 => "K. Voskarides" 2 => "D.P. Gale" 3 => "L. Damianou" 4 => "C. Patsias" 5 => "M. Zavros" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2215/CJN.09541010" "Revista" => array:6 [ "tituloSerie" => "Clin J Am Soc Nephrol" "fecha" => "2011" "volumen" => "6" "paginaInicial" => "1436" "paginaFinal" => "1446" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21566112" "web" => "Medline" ] ] ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib0115" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Acquired and genetic complement abnormalities play a critical role in dense deposit disease and other C3 glomerulopathies" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Servais" 1 => "L.H. Noel" 2 => "L.T. Roumenina" 3 => "M. le Quintrec" 4 => "S. Ngo" 5 => "M.A. Dragon-Durey" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/ki.2012.63" "Revista" => array:6 [ "tituloSerie" => "Kidney Int" "fecha" => "2012" "volumen" => "82" "paginaInicial" => "454" "paginaFinal" => "464" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22456601" "web" => "Medline" ] ] ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0120" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "C3 deposition glomerulopathy due to a functional factor H defect" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. Habbig" 1 => "M.J. Mihatsch" 2 => "S. Heinen" 3 => "B. Beck" 4 => "M. Emmel" 5 => "C. Skerka" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/ki.2008.354" "Revista" => array:6 [ "tituloSerie" => "Kidney Int" "fecha" => "2009" "volumen" => "75" "paginaInicial" => "1230" "paginaFinal" => "1234" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18633337" "web" => "Medline" ] ] ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib0125" "etiqueta" => "25" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Human C3 mutation reveals a mechanism of dense deposit disease pathogenesis and provides insights into complement activation and regulation" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R. Martínez-Barricarte" 1 => "M. Heurich" 2 => "F. Valdes-Cañedo" 3 => "E. Vazquez-Martul" 4 => "E. Torreira" 5 => "T. Montes" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1172/JCI43343" "Revista" => array:6 [ "tituloSerie" => "J Clin Invest" "fecha" => "2010" "volumen" => "120" "paginaInicial" => "3702" "paginaFinal" => "3712" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20852386" "web" => "Medline" ] ] ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib0130" "etiqueta" => "26" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Pathogenesis of the C3 glomerulopathies and reclassification of MPGN" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "A. Bomback" 1 => "G.B. Appel" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/nrneph.2012.213" "Revista" => array:6 [ "tituloSerie" => "Nat Rev Nephrol" "fecha" => "2012" "volumen" => "8" "paginaInicial" => "634" "paginaFinal" => "642" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23026947" "web" => "Medline" ] ] ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bib0135" "etiqueta" => "27" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Causes of alternative pathway dysregulation in dense deposit disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "Y. Zhang" 1 => "N.C. Meyer" 2 => "K. Wang" 3 => "C. Nishimura" 4 => "K. Frees" 5 => "M. Jones" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2215/CJN.07900811" "Revista" => array:6 [ "tituloSerie" => "Clin J Am Soc Nephrol" "fecha" => "2012" "volumen" => "7" "paginaInicial" => "265" "paginaFinal" => "274" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22223606" "web" => "Medline" ] ] ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib0140" "etiqueta" => "28" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The losartan renal protection study—rationale, study design and baseline characteristics of RENAAL (Reduction of endpoints in NIDDM with the angiotensin II antagonist losartan)" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "B.M. Brenner" 1 => "M.E. Cooper" 2 => "D. de Zeeuw" 3 => "J.P. Grunfeld" 4 => "W.F. Keane" 5 => "K. Kurokawa" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3317/jraas.2000.062" "Revista" => array:6 [ "tituloSerie" => "J Renin Angiotensin Aldosterone Syst" "fecha" => "2000" "volumen" => "1" "paginaInicial" => "328" "paginaFinal" => "335" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11967819" "web" => "Medline" ] ] ] ] ] ] ] ] 28 => array:3 [ "identificador" => "bib0145" "etiqueta" => "29" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Renoprotective properties of ACE-inhibition in nondiabetic nephropathies with nonnephrotic proteinuria" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P. Ruggenenti" 1 => "A. Perna" 2 => "G. Gherardi" 3 => "G. Garini" 4 => "C. Zoccali" 5 => "M. Salvadori" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(98)10363-X" "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "1999" "volumen" => "354" "paginaInicial" => "359" "paginaFinal" => "364" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10437863" "web" => "Medline" ] ] ] ] ] ] ] ] 29 => array:3 [ "identificador" => "bib0150" "etiqueta" => "30" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Production of biologically active complement factor H in therapeutically useful quantities" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "C.Q. Schmidt" 1 => "F.C. Slingsby" 2 => "A. Richards" 3 => "P.N. Barlow" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.pep.2010.12.002" "Revista" => array:6 [ "tituloSerie" => "Protein Expr Purif" "fecha" => "2011" "volumen" => "76" "paginaInicial" => "254" "paginaFinal" => "263" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21146613" "web" => "Medline" ] ] ] ] ] ] ] ] 30 => array:3 [ "identificador" => "bib0155" "etiqueta" => "31" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Recurrent dense deposit disease after renal transplantation: an emerging role for complementary therapies" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "J.A. McCaughan" 1 => "D.M. O’Rourke" 2 => "A.E. Courtney" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1600-6143.2011.03923.x" "Revista" => array:6 [ "tituloSerie" => "Am J Transplant" "fecha" => "2012" "volumen" => "12" "paginaInicial" => "1046" "paginaFinal" => "1051" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22233157" "web" => "Medline" ] ] ] ] ] ] ] ] 31 => array:3 [ "identificador" => "bib0160" "etiqueta" => "32" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Eculizumab for dense deposit disease and C3 glomerulonephritis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A.S. Bomback" 1 => "R.J. Smith" 2 => "G.R. Barile" 3 => "Y. Zhang" 4 => "E.C. Heher" 5 => "L. Herlitz" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2215/CJN.12901211" "Revista" => array:6 [ "tituloSerie" => "Clin J Am Soc Nephrol" "fecha" => "2012" "volumen" => "7" "paginaInicial" => "748" "paginaFinal" => "756" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22403278" "web" => "Medline" ] ] ] ] ] ] ] ] 32 => array:3 [ "identificador" => "bib0165" "etiqueta" => "33" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Multicenter phase 3 study of the complement inhibitor eculizumab for the treatment of patients with paroxysmal nocturnal hemoglobinuria" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R.A. Brodsky" 1 => "N.S. Young" 2 => "E. Antonioli" 3 => "A.M. Risitano" 4 => "H. Schrezenmeier" 5 => "J. Schubert" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1182/blood-2007-06-094136" "Revista" => array:6 [ "tituloSerie" => "Blood" "fecha" => "2008" "volumen" => "111" "paginaInicial" => "1840" "paginaFinal" => "1847" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18055865" "web" => "Medline" ] ] ] ] ] ] ] ] 33 => array:3 [ "identificador" => "bib0170" "etiqueta" => "34" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Eculizumab in the treatment of atypical hemolytic uremic syndrome in infants" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "G. Ariceta" 1 => "B. Arrizabalaga" 2 => "M. Aguirre" 3 => "E. Morteruel" 4 => "M. Lopez-Trascasa" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1053/j.ajkd.2011.11.027" "Revista" => array:6 [ "tituloSerie" => "Am J Kidney Dis" "fecha" => "2012" "volumen" => "59" "paginaInicial" => "707" "paginaFinal" => "710" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22196848" "web" => "Medline" ] ] ] ] ] ] ] ] 34 => array:3 [ "identificador" => "bib0175" "etiqueta" => "35" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Eculizumab for the treatment of preeclampsia/HELLP syndrome" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "R.M. Burwick" 1 => "B.B. Feinberg" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.placenta.2012.11.014" "Revista" => array:6 [ "tituloSerie" => "Placenta" "fecha" => "2013" "volumen" => "34" "paginaInicial" => "201" "paginaFinal" => "203" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23228435" "web" => "Medline" ] ] ] ] ] ] ] ] 35 => array:3 [ "identificador" => "bib0180" "etiqueta" => "36" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Combined complete C5 and partial C4 deficiency in humans: clinical consequences and complement-mediated functions in vitro" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "A. Gianella-Borradori" 1 => "L. Borradori" 2 => "P.M. Schneider" 3 => "E. Gautier" 4 => "P.J. Späth" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Clin Immunol Immunopathol" "fecha" => "1990" "volumen" => "55" "paginaInicial" => "41" "paginaFinal" => "55" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2306879" "web" => "Medline" ] ] ] ] ] ] ] ] 36 => array:3 [ "identificador" => "bib0185" "etiqueta" => "37" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Insufficient protection by Neisseria meningitidis vaccination alone during eculizumab therapy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "A. Bouts" 1 => "L. Monnens" 2 => "J.C. Davin" 3 => "G. Struijk" 4 => "L. Spanjaard" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00467-011-1929-3" "Revista" => array:6 [ "tituloSerie" => "Pediatr Nephrol" "fecha" => "2011" "volumen" => "26" "paginaInicial" => "1919" "paginaFinal" => "1920" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21643943" "web" => "Medline" ] ] ] ] ] ] ] ] 37 => array:3 [ "identificador" => "bib0190" "etiqueta" => "38" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Eculizumab for the treatment of densedeposit disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "M. Vivarelli" 1 => "A. Pasini" 2 => "F. Emma" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMc1111953" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2012" "volumen" => "366" "paginaInicial" => "1163" "paginaFinal" => "1165" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22435383" "web" => "Medline" ] ] ] ] ] ] ] ] 38 => array:3 [ "identificador" => "bib0195" "etiqueta" => "39" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Eculizumab in a patient with dense-deposit disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "E. Daina" 1 => "M. Noris" 2 => "G. Remuzzi" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMc1112273" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2012" "volumen" => "366" "paginaInicial" => "1161" "paginaFinal" => "1163" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22435382" "web" => "Medline" ] ] ] ] ] ] ] ] 39 => array:3 [ "identificador" => "bib0200" "etiqueta" => "40" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Eculizumab and refractory membranoproliferative glomerulonephritis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. Radhakrishnan" 1 => "A. Lunn" 2 => "M. Kirschfink" 3 => "P. Thorner" 4 => "D. Hebert" 5 => "V. Langlois" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMc1106619" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2012" "volumen" => "366" "paginaInicial" => "1165" "paginaFinal" => "1166" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22435384" "web" => "Medline" ] ] ] ] ] ] ] ] 40 => array:3 [ "identificador" => "bib0205" "etiqueta" => "41" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Eculizumab and recurrent C3 glomerulonephritis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "S. Gurkan" 1 => "B. Fyfe" 2 => "L. Weiss" 3 => "X. Xiao" 4 => "Y. Zhang" 5 => "R.J. Smith" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00467-013-2503-y" "Revista" => array:6 [ "tituloSerie" => "Pediatr Nephrol" "fecha" => "2013" "volumen" => "28" "paginaInicial" => "1975" "paginaFinal" => "1981" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23689905" "web" => "Medline" ] ] ] ] ] ] ] ] 41 => array:3 [ "identificador" => "bib0210" "etiqueta" => "42" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Use of eculizumab for atypical haemolytic uraemic syndrome and C3 glomerulopathies" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "J. Zuber" 1 => "F. Fakhouri" 2 => "L. Roumenina" 3 => "C. Loirat" 4 => "V. Frémeaux-Bacchi" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/nrneph.2012.214" "Revista" => array:6 [ "tituloSerie" => "Nat Rev Nephrol" "fecha" => "2012" "volumen" => "8" "paginaInicial" => "643" "paginaFinal" => "657" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23026949" "web" => "Medline" ] ] ] ] ] ] ] ] 42 => array:3 [ "identificador" => "bib0215" "etiqueta" => "43" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Glomerulopatías C3. Una nueva perspectiva en enfermedades glomerulares" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "C. Rabasco-Ruiz" 1 => "A. Huerta-Arroyo" 2 => "J. Caro-Espada" 3 => "E. Gutiérrez-Martínez" 4 => "M. Praga-Terente" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3265/Nefrologia.pre2012.Nov.11802" "Revista" => array:6 [ "tituloSerie" => "Nefrologia" "fecha" => "2013" "volumen" => "33" "paginaInicial" => "164" "paginaFinal" => "170" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23511752" "web" => "Medline" ] ] ] ] ] ] ] ] 43 => array:3 [ "identificador" => "bib0220" "etiqueta" => "44" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Membranoproliferative glomerulonephritis with isolated C3 deposits: case report and literature review" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "S. Darouich" 1 => "R. Goucha" 2 => "M.H. Jaafoura" 3 => "S. Zekri" 4 => "A. Kheder" 5 => "H. Ben Maiz" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3109/01913123.2010.532902" "Revista" => array:6 [ "tituloSerie" => "Ultrastruct Pathol" "fecha" => "2011" "volumen" => "35" "paginaInicial" => "42" "paginaFinal" => "46" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21265634" "web" => "Medline" ] ] ] ] ] ] ] ] 44 => array:3 [ "identificador" => "bib0225" "etiqueta" => "45" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "C3 glomerulonephritis/CFHR5 nephropathy is an endemic disease in Cyprus: clinical and molecular findings in 21 families" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "C. Deltas" 1 => "D. Gale" 2 => "T. Cook" 3 => "K. Voskarides" 4 => "Y. Athanasiou" 5 => "A. Pierides" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Adv Exp Med Biol" "fecha" => "2013" "volumen" => "735" "paginaInicial" => "189" "paginaFinal" => "196" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23402027" "web" => "Medline" ] ] ] ] ] ] ] ] 45 => array:3 [ "identificador" => "bib0230" "etiqueta" => "46" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "C3 glomerulonephritis associated with a missense mutation in the factor H gene" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "K. Sugimoto" 1 => "S. Fujita" 2 => "K. Miyazaki" 3 => "M. Okada" 4 => "T. Takemura" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Tohoku J Exp Med" "fecha" => "2012" "volumen" => "227" "paginaInicial" => "211" "paginaFinal" => "215" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22790979" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/22548874/0000021400000005/v1_201406010020/S2254887414000344/v1_201406010020/en/main.assets" "Apartado" => array:4 [ "identificador" => "1904" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Clinical Up-Date" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/22548874/0000021400000005/v1_201406010020/S2254887414000344/v1_201406010020/en/main.pdf?idApp=WRCEE&text.app=https://revclinesp.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2254887414000344?idApp=WRCEE"]

Statistics

Clinical up-date

C3 glomerulopathy: A new complement-based entity

Glomerulopatía C3: una nueva entidad basada en el complemento

A. de Lorenzo

Corresponding author

doctorberto@hotmail.com

Corresponding author.

, S. Tallón, B. Hernández-Sevillano, G. de Arriba

Servicio de Nefrología, Hospital Universitario de Guadalajara, Departamento de Medicina, Universidad de Alcalá, Alcalá de Henares, Madrid, Spain

Read

1001

Times
was read the article

Total PDF

995

Total HTML

Share statistics

 array:23 [
  "pii" => "S2254887414000344"
  "issn" => "22548874"
  "doi" => "10.1016/j.rceng.2014.01.009"
  "estado" => "S300"
  "fechaPublicacion" => "2014-06-01"
  "aid" => "908"
  "copyright" => "Elsevier Espa&#241;a&#44; S&#46;L&#46;. All rights reserved"
  "copyrightAnyo" => "2013"
  "documento" => "simple-article"
  "crossmark" => 0
  "subdocumento" => "crp"
  "cita" => "Rev Clin Esp. 2014;214:266-74"
  "abierto" => array:3 [
    "ES" => false
    "ES2" => false
    "LATM" => false
  ]
  "gratuito" => false
  "lecturas" => array:2 [
    "total" => 992
    "formatos" => array:2 [
      "HTML" => 990
      "PDF" => 2
    ]
  ]
  "Traduccion" => array:1 [
    "es" => array:19 [
      "pii" => "S0014256514000228"
      "issn" => "00142565"
      "doi" => "10.1016/j.rce.2014.01.016"
      "estado" => "S300"
      "fechaPublicacion" => "2014-06-01"
      "aid" => "908"
      "copyright" => "Elsevier Espa&#241;a&#44; S&#46;L&#46;"
      "documento" => "simple-article"
      "crossmark" => 0
      "subdocumento" => "crp"
      "cita" => "Rev Clin Esp. 2014;214:266-74"
      "abierto" => array:3 [
        "ES" => false
        "ES2" => false
        "LATM" => false
      ]
      "gratuito" => false
      "lecturas" => array:2 [
        "total" => 4120
        "formatos" => array:2 [
          "HTML" => 3623
          "PDF" => 497
        ]
      ]
      "es" => array:13 [
        "idiomaDefecto" => true
        "cabecera" => "<span class="elsevierStyleTextfn">Actualizaci&#243;n cl&#237;nica</span>"
        "titulo" => "Glomerulopat&#237;a C3&#58; una nueva entidad basada en el complemento"
        "tienePdf" => "es"
        "tieneTextoCompleto" => "es"
        "tieneResumen" => array:2 [
          0 => "es"
          1 => "en"
        ]
        "paginas" => array:1 [
          0 => array:2 [
            "paginaInicial" => "266"
            "paginaFinal" => "274"
          ]
        ]
        "titulosAlternativos" => array:1 [
          "en" => array:1 [
            "titulo" => "C3 glomerulopathy&#58; A new complement-based entity"
          ]
        ]
        "contieneResumen" => array:2 [
          "es" => true
          "en" => true
        ]
        "contieneTextoCompleto" => array:1 [
          "es" => true
        ]
        "contienePdf" => array:1 [
          "es" => true
        ]
        "resumenGrafico" => array:2 [
          "original" => 0
          "multimedia" => array:7 [
            "identificador" => "fig0005"
            "etiqueta" => "Figura 1"
            "tipo" => "MULTIMEDIAFIGURA"
            "mostrarFloat" => true
            "mostrarDisplay" => false
            "figura" => array:1 [
              0 => array:4 [
                "imagen" => "gr1.jpeg"
                "Alto" => 1362
                "Ancho" => 1652
                "Tamanyo" => 93878
              ]
            ]
            "descripcion" => array:1 [
              "es" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">V&#237;a alternativa del complemento&#46; En la activaci&#243;n de la v&#237;a alternativa del complemento&#44; C3 convertasa escinde C3 en C3a y C3b&#44; siendo este &#250;ltimo&#44; a su vez&#44; un potente amplificador y generador de C3 convertasa&#46; Este proceso est&#225; regulado por factor<span class="elsevierStyleHsp" style=""></span>H&#44; que inhibe la C3 convertasa&#44; y factor<span class="elsevierStyleHsp" style=""></span>I&#44; que convierte C3b en C3b inactivo&#44; frenando as&#237; la cascada&#46; Adem&#225;s&#44; de los productos derivados de la acci&#243;n de C3 convertasa se genera C5 convertasa&#46; Esta enzima escinde C5 en C5a y C5b&#46; La uni&#243;n de C5b con C6-C9 forma el complejo de ataque a membrana &#40;CAM&#41; con actividad quimiot&#225;ctica en las superficies celulares&#44; resultando en la lisis celular&#46;</p>"
            ]
          ]
        ]
        "autores" => array:1 [
          0 => array:2 [
            "autoresLista" => "A&#46; de Lorenzo, S&#46; Tall&#243;n, B&#46; Hern&#225;ndez-Sevillano, G&#46; de Arriba"
            "autores" => array:4 [
              0 => array:2 [
                "nombre" => "A&#46;"
                "apellidos" => "de Lorenzo"
              ]
              1 => array:2 [
                "nombre" => "S&#46;"
                "apellidos" => "Tall&#243;n"
              ]
              2 => array:2 [
                "nombre" => "B&#46;"
                "apellidos" => "Hern&#225;ndez-Sevillano"
              ]
              3 => array:2 [
                "nombre" => "G&#46;"
                "apellidos" => "de Arriba"
              ]
            ]
          ]
        ]
      ]
      "idiomaDefecto" => "es"
      "Traduccion" => array:1 [
        "en" => array:9 [
          "pii" => "S2254887414000344"
          "doi" => "10.1016/j.rceng.2014.01.009"
          "estado" => "S300"
          "subdocumento" => ""
          "abierto" => array:3 [
            "ES" => false
            "ES2" => false
            "LATM" => false
          ]
          "gratuito" => false
          "lecturas" => array:1 [
            "total" => 0
          ]
          "idiomaDefecto" => "en"
          "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2254887414000344?idApp=WRCEE"
        ]
      ]
      "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0014256514000228?idApp=WRCEE"
      "url" => "/00142565/0000021400000005/v2_201406130025/S0014256514000228/v2_201406130025/es/main.assets"
    ]
  ]
  "itemAnterior" => array:19 [
    "pii" => "S2254887413001471"
    "issn" => "22548874"
    "doi" => "10.1016/j.rceng.2013.12.003"
    "estado" => "S300"
    "fechaPublicacion" => "2014-06-01"
    "aid" => "861"
    "copyright" => "Elsevier Espa&#241;a&#44; S&#46;L&#46;"
    "documento" => "simple-article"
    "crossmark" => 0
    "subdocumento" => "crp"
    "cita" => "Rev Clin Esp. 2014;214:258-65"
    "abierto" => array:3 [
      "ES" => false
      "ES2" => false
      "LATM" => false
    ]
    "gratuito" => false
    "lecturas" => array:2 [
      "total" => 287
      "HTML" => 287
    ]
    "en" => array:13 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Clinical up-date</span>"
      "titulo" => "Radiographic patterns in the diagnostic approach to organizing pneumonia"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "tieneResumen" => array:2 [
        0 => "en"
        1 => "es"
      ]
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "258"
          "paginaFinal" => "265"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "es" => array:1 [
          "titulo" => "Patrones radiol&#243;gicos en la aproximaci&#243;n diagn&#243;stica a la neumon&#237;a organizativa"
        ]
      ]
      "contieneResumen" => array:2 [
        "en" => true
        "es" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:7 [
          "identificador" => "fig0015"
          "etiqueta" => "Figure 3"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr3.jpeg"
              "Alto" => 1051
              "Ancho" => 1344
              "Tamanyo" => 174719
            ]
          ]
          "descripcion" => array:1 [
            "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Other radiological patterns&#46; &#40;A&#41; Axial slice of chest computed tomography in which ill-defined nodular opacities of various sizes can be observed&#44; which do not exceed 1 centimeter&#44; with patchy distribution and no regional predominance&#46; &#40;B&#41; Axial slice of chest computed tomography in which patchy consolidations with peripheral ground-glass attenuation can be observed&#44; illustrating an example of the &#8220;halo sign&#8221; &#40;white arrows&#41;&#46; &#40;C&#41; Coronal reconstruction of chest CT in which a central area of ground-glass attenuation &#40;star white&#41; with a peripheral area of consolidation can be observed in the lower right lobe&#44; forming an almost complete ring&#44; suggesting an &#8220;inverted halo&#8221; or &#8220;atoll&#8221; sign &#40;white arrows&#41;&#46; &#40;D&#41; Axial slice of chest CT in which a cobblestone pattern can be seen&#44; distributed through both lungs&#44; predominantly in the lower lobes&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "C&#46; Utrilla Contreras, M&#46; Fern&#225;ndez-Velilla Pe&#241;a, F&#46; Garc&#237;a R&#237;o, M&#46;I&#46; Torres S&#225;nchez"
          "autores" => array:4 [
            0 => array:2 [
              "nombre" => "C&#46;"
              "apellidos" => "Utrilla Contreras"
            ]
            1 => array:2 [
              "nombre" => "M&#46;"
              "apellidos" => "Fern&#225;ndez-Velilla Pe&#241;a"
            ]
            2 => array:2 [
              "nombre" => "F&#46;"
              "apellidos" => "Garc&#237;a R&#237;o"
            ]
            3 => array:2 [
              "nombre" => "M&#46;I&#46;"
              "apellidos" => "Torres S&#225;nchez"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "Traduccion" => array:1 [
      "es" => array:9 [
        "pii" => "S001425651300369X"
        "doi" => "10.1016/j.rce.2013.10.015"
        "estado" => "S300"
        "subdocumento" => ""
        "abierto" => array:3 [
          "ES" => false
          "ES2" => false
          "LATM" => false
        ]
        "gratuito" => false
        "lecturas" => array:1 [
          "total" => 0
        ]
        "idiomaDefecto" => "es"
        "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S001425651300369X?idApp=WRCEE"
      ]
    ]
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2254887413001471?idApp=WRCEE"
    "url" => "/22548874/0000021400000005/v1_201406010020/S2254887413001471/v1_201406010020/en/main.assets"
  ]
  "en" => array:20 [
    "idiomaDefecto" => true
    "cabecera" => "<span class="elsevierStyleTextfn">Clinical up-date</span>"
    "titulo" => "C3 glomerulopathy&#58; A new complement-based entity"
    "tieneTextoCompleto" => true
    "paginas" => array:1 [
      0 => array:2 [
        "paginaInicial" => "266"
        "paginaFinal" => "274"
      ]
    ]
    "autores" => array:1 [
      0 => array:4 [
        "autoresLista" => "A&#46; de Lorenzo, S&#46; Tall&#243;n, B&#46; Hern&#225;ndez-Sevillano, G&#46; de Arriba"
        "autores" => array:4 [
          0 => array:4 [
            "nombre" => "A&#46;"
            "apellidos" => "de Lorenzo"
            "email" => array:1 [
              0 => "doctorberto&#64;hotmail&#46;com"
            ]
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">¿</span>"
                "identificador" => "cor0005"
              ]
            ]
          ]
          1 => array:2 [
            "nombre" => "S&#46;"
            "apellidos" => "Tall&#243;n"
          ]
          2 => array:2 [
            "nombre" => "B&#46;"
            "apellidos" => "Hern&#225;ndez-Sevillano"
          ]
          3 => array:2 [
            "nombre" => "G&#46;"
            "apellidos" => "de Arriba"
          ]
        ]
        "afiliaciones" => array:1 [
          0 => array:2 [
            "entidad" => "Servicio de Nefrolog&#237;a&#44; Hospital Universitario de Guadalajara&#44; Departamento de Medicina&#44; Universidad de Alcal&#225;&#44; Alcal&#225; de Henares&#44; Madrid&#44; Spain"
            "identificador" => "aff0005"
          ]
        ]
        "correspondencia" => array:1 [
          0 => array:3 [
            "identificador" => "cor0005"
            "etiqueta" => "&#8270;"
            "correspondencia" => "Corresponding author&#46;"
          ]
        ]
      ]
    ]
    "titulosAlternativos" => array:1 [
      "es" => array:1 [
        "titulo" => "Glomerulopat&#237;a C3&#58; una nueva entidad basada en el complemento"
      ]
    ]
    "resumenGrafico" => array:2 [
      "original" => 0
      "multimedia" => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 1362
            "Ancho" => 1652
            "Tamanyo" => 95391
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Alternative complement pathway&#46; In the activation of the alternative complement pathway&#44; C3 convertase cleaves C3 into C3a and C3b&#44; the latter of which is a potent C3 convertase amplifier and generator&#46; This process is regulated by factor H &#40;which inhibits C3 convertase&#41; and factor I &#40;which converts C3b into inactive C3b&#44; thereby slowing the cascade&#41;&#46; In addition&#44; C5 convertase is generated from the products derived from the action of C3 convertase&#46; This enzyme cleaves C5 into C5a and C5b&#46; The binding of C5b with C6&#8211;C9 forms the membrane attack complex &#40;MAC&#41; with chemotactic activity in the cell surfaces&#44; resulting in cell lysis&#46;</p>"
        ]
      ]
    ]
    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">The clinical problem</span><p id="par0005" class="elsevierStylePara elsevierViewall">Advances in the understanding of alternative complement pathway abnormalities have led to the recent discovery of a new entity in the setting of glomerular diseases&#46; This entity is known as C3 glomerulopathy&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#8211;4</span></a> The onset of this new disease makes the classification of membranoproliferative glomerulonephritis obsolete and opens a new field of research in the setting of its treatment using new biological therapies such as the anti-C5 monoclonal antibody eculizumab&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">C3 glomerulopathy</span><p id="par0010" class="elsevierStylePara elsevierViewall">The term C3 glomerulopathy includes 2 subtypes&#58; dense-deposit disease &#40;DDD&#41; and C3 glomerulonephritis &#40;GNC3&#41; itself&#44; 2 entities that have in common the isolated deposit of complement 3 &#40;C3&#41; fraction&#44; i&#46;e&#46;&#44; in the absence of immunoglobulins&#44; and which&#44; in turn&#44; have ultrastructural differences that allow them to be differentiated&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Alternative complement pathway abnormalities cause the isolated deposit of factor C3 in the mesangium and capillary wall&#44; which is characteristic of membranoproliferative glomerulonephritis and is produced without concomitant immunoglobulin deposit&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;6</span></a> The clinical expression is a microscopic hematuria-proteinuria syndrome with a variable degree of proteinuria&#44; which can reach the nephrotic range&#46; If electron-dense deposits visible by electron microscope are identified&#44; then the disease is classified as DDD&#46; If these deposits are absent&#44; the disease is classified as GNC3&#44; in which case the deposits are very similar to those of glomerulonephritis mediated by immune complexes &#40;located at the mesangial&#44; subendothelial&#44; subepithelial and&#47;or intramembranous level&#41;&#44; although without them being present&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Dense-deposit disease</span><p id="par0020" class="elsevierStylePara elsevierViewall">This is an extremely rare disease &#40;2&#8211;3 cases per million&#41; that mainly affects children and young adults and is slightly more common in women &#40;3&#58;2 ratio&#41;&#46; Clinically&#44; the disease presents with varying amounts of proteinuria and hematuria&#46; The essential characteristic that defines and differentiates this entity is the presence of electron-dense deposits in the glomerular basement membrane &#40;GBM&#41; and mesangium&#44; and not the presence or absence of a membranoproliferative pattern observed under optical microscopy consisting of the thickening of the GBM along with the proliferation of mesangial cells &#40;which is only present in 25&#37; of affected individuals&#41;&#46; The most common histological pattern is mesangial proliferation &#40;45&#37;&#41;&#46; For this reason&#44; we can say that the term membranoproliferative glomerulonephritis &#40;MPGN&#41; type II has become obsolete&#46; In fact&#44; MPGN is currently classified as mediated by immune complexes &#40;which include types I and III&#44; caused most often by the hepatitis B and C viruses whose antigenemia causes the depositing of immune complexes at the glomerular level&#41;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8&#8211;10</span></a> and by the complement &#40;DDD and GNC3&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; Given that there is a deregulation of the alternative complement pathway in the origin of DDD&#44; 60&#8211;80&#37; of cases have complement consumption data manifested by low serum levels of C3 and degradation products&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">To confirm a suspected diagnosis&#44; a renal biopsy is essential&#46; Here the diagnostic criterion is the presence of electron-dense deposits in the GBM&#44; along with direct immunofluorescence for C3 and the absence of immunoglobulin deposits in most cases&#44; as well as a reduction in plasma C3 levels&#44; whose levels need to be determined&#46; Once the diagnosis has been confirmed and depending on the availability at each center&#44; a complement study should be requested&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Approximately 50&#37; of affected individuals progress to end-stage renal disease &#40;ESRD&#41; at 10 years after diagnosis&#44; although the course is more aggressive and rapid in young patients and women&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12&#44;13</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">C3 glomerulonephritis</span><p id="par0035" class="elsevierStylePara elsevierViewall">The concept of GNC3 was coined in 2007 when Servais et al&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> described what is known as &#8220;primary glomerulonephritis with isolated C3 deposits&#8221;&#46; The fundamental requirement for the diagnosis of this entity&#44; as with DDD&#44; was the isolated deposits of C3 on immunofluorescence&#46; It was noteworthy that these patients had none of the typical characteristics of DDD&#44; and in fact the deposits resembled those of MPGN types I and III&#44; with the significant exception that they lacked immune complexes&#46; Reduced serum C3 levels appear less frequently than in DDD in 40&#37; of cases&#46; There are no major differences in terms of the clinical presentation between DDD and GNC3&#44; although GNC3 has a slightly better prognosis&#59; approximately 20&#37; of patients progress to ESRD at 10 years&#44; and 30&#37; progress to stages 3&#8211;4 CKD&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p></span></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Etiopathogenesis</span><p id="par0040" class="elsevierStylePara elsevierViewall">The complement system is a mechanism mainly involved in defending against infections &#40;mainly gram negative germs&#41; and tumor cells&#46; The system consists of approximately 30 factors that are mostly plasma proteins&#46; Complement activation can be initiated by 3 different pathways &#40;classical&#44; alternative and lectin&#41;&#46; It involves changes in particular components that result in chain reactions&#44; in such a way that active products are generated that&#44; in addition to ensuring that the chain continues to the next reaction&#44; can have important biological activities in the body&#39;s defense&#46; All these are due to the fact that most complement factors are proteolytic in nature&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> The alternative complement pathway is generally active in circulation&#44; although at low levels due to regulatory mechanisms that prevent self-harm&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">There are 2 main regulators of this pathway&#58; factors H and I&#44; whose abnormalities &#40;either inherited or acquired&#41; create an imbalance between activating and inhibiting factors &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; DDD and GNC3 have a common etiopathogenic origin in the mutations of the alternative complement pathway&#46; A disorder in the regulation of C3 and C5 convertases generates an unbridled activation of the system and a considerable quantity of C3b and membrane attack complex &#40;MAC&#41;&#44; which ends by accumulating in the glomerular capillary wall&#44; ultimately generating C3 glomerulopathy&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> DDD and GNC3 can probably be differentiated by the degree to which one or the other convertase is affected&#46; It seems that in the case of DDD&#44; the predominant disorder is at the C3 convertase level&#44; while the origin of GNC3 is mainly due to a C5 convertase disorder&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">In recent years&#44; there have been numerous publications on this disease&#46; Several mutations of genes involved in this process of improper activation of the complement have been reported&#44; such as CFHR5&#44; factor H&#44; factor I and factor C3&#44;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">16&#8211;19</span></a> although the majority of patients have polymorphisms of several genes&#46; These polymorphisms generate new epitopes that determine the development of autoantibodies known as C3 nephritic factor&#44; which acts as a stabilizer of C3 convertase&#44; preventing the action of physiological regulators such as factor H&#46; Thus&#44; for DDD&#44; 60&#8211;80&#37; of cases progress with complement consumption data manifested by low serum levels of C3 and products resulting from its degradation&#46; In GNC3&#44; the percentage of reduced C3 is somewhat lower&#44; appearing in 40&#37; of patients&#46; Sethi et al&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> reported on a series of 12 patients with GNC3 and alternative complement pathway disorder&#46; Initially&#44; 9 of the 12 patients with GNC3 were classified as having MPGN I &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>4&#41;&#44; MPGN III &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#41; and postinfectious glomerulonephritis &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>4&#41;&#46; The Sethi group showed that the proteomic profile of GNC3 was similar to that of DDD &#40;with a predominance of C3 and final complement pathway components&#41;&#46; This result supports the theory that the presence of isolated C3 is the main marker of alternative complement pathway dysfunction in C3 glomerulopathy&#44; regardless of its optical or ultrastructural histology&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">The greatest contribution from the genotypic and phenotypic points of view has been the data from 2 recently published cohorts&#46; The first&#44; published in 2010 by Gale et al&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> describes 91 patients belonging to 16 families of Cypriot origin with a CFHR5 mutation that encodes protein 5 related to factor H&#46; The mutation was more common in men than in women &#40;80&#37; vs&#46; 21&#37;&#41;&#46; In this case&#44; the condition was labeled nephropathy CFHR5&#44; characterized by persistent microscopic hematuria with gross hematuria coinciding with intercurrent upper respiratory infection &#40;imitating the typical presentation of nephropathy by IgA deposits&#41;&#44; as well as proteinuria in 38&#37; of the cases&#44; with progression to ESRD more likely in these cases&#44; especially for males &#40;78&#37; vs&#46; 22&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">In 2012&#44; Servais et al&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> studied a French cohort of 85 patients with C3 glomerulopathy&#44; 56 of them with GNC3 and 29 with DDD&#46; Sixty percent of the patients had microscopic hematuria&#59; the proteinuria levels were slightly lower in the cases with GNC3 than in those with DDD &#40;3&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;3<span class="elsevierStyleHsp" style=""></span>g vs&#46; 5&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;5<span class="elsevierStyleHsp" style=""></span>g&#41;&#46; Although both conditions are present in the young population&#44; the patients with GNC3 were older &#40;30&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>19&#46;3 vs&#46; 18&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>17&#46;7 years&#41;&#46; These authors were also the first to shed light on the possible etiological origin of GNC3&#44; given that 31&#37; of their patients had a mutation in factor H&#44; factor I or in the membrane cofactor protein&#46; They also observed that C3 nephritic factor was less common in GNC3 than in DDD &#40;45&#37; vs&#46; 86&#37;&#41;&#44; which also occurred with reduced serum C3 levels &#40;86&#46;4&#37; vs&#46; 45&#46;3&#37;&#41;&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Habbig et al&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> reported on a family with 2 siblings of consanguineous parents with hematuria and proteinuria since childhood&#46; Both siblings had reduced levels of serum C3 and complement regulatory factor B&#46; A mesangial deposit of C3 and C5b-9 was observed in the biopsy&#44; and numerous mesangial&#44; intramembranous and subendothelial deposits were observed under electron microscopy&#46; Genetic screening for factor H mutations showed that both children were homozygous for a lysine deletion&#46; This deletion leads to a critical reduction of this cofactor inhibitor&#46; Additionally&#44; both patients and their healthy mother were positive for C3 nephritic factor&#46; In 2010&#44; Mart&#237;nez-Barricarte et al&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> published a report on a family with DDD and a C3 mutation&#46; This mutation conferred resistance to C3 against its excision by C3 convertase&#44; thereby preventing the formation of activated C3b&#46; The disease in this family was caused exclusively by dysregulation in the fluid phase of the alternative pathway with no contribution from the terminal complement cascade &#40;TCC&#41;&#46; In contrast&#44; the GNC3 described in the Cypriot families by Gale et al&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> and in the siblings by Habbig et al&#46; were associated with the C5 convertase disorder and the subsequent activation of the TCC &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">The alternative complement pathway disorder could also be due to acquired causes that trigger the formation of 2 types of antibodies &#40;Ab&#41;&#44; various inhibitors &#40;antifactor H Ab and antifactor I Ab&#41; and others that directly stimulate complement activation such as C3 nephritic factor&#44; an IgG autoantibody that stabilizes C3 convertase&#44; extending its half-life and enzymatic activity&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Assessment of patients with C3 glomerulopathy</span><p id="par0075" class="elsevierStylePara elsevierViewall">In the clinical assessment of patients with C3 glomerulopathy&#44; the identification of the underlying defect in the alternative complement pathway can be very useful&#46; It allows a family study to be carried out and prevents damage in relatives with subclinical involvement&#46; Experts recommend measuring serum levels of CH50&#44; C3&#44; C3d&#44; C4&#44; factor H and factor I&#44; studying their mutations&#44; assessing the presence of autoantibodies such as C3 nephritic factor and conducting functional trials of the alternative complement pathway &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">20&#44;26&#44;27</span></a></p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Treatment</span><p id="par0080" class="elsevierStylePara elsevierViewall">Despite significant progress in the understanding of the underlying mechanisms&#44; advances in treatment have not enabled the development of effective compounds&#46; Various treatment modalities are used with varying degrees of effectiveness&#46; Examples of treatments include renin&#8211;angiotensin axis blockade&#44; plasmapheresis with plasma infusion and cellular immunosuppressants&#46; The exception to this rule is biological therapy directed using the anti-C5 monoclonal antibody eculizumab&#46;</p><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Renin&#8211;angiotensin axis inhibitors</span><p id="par0085" class="elsevierStylePara elsevierViewall">The current evidence on chronic kidney disease and glomerulopathy with nonselective proteinuria&#44; as well as the data obtained by Servais et al&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> in this group of diseases&#44; support the use of angiotensin-converting enzyme inhibitors &#40;ACEI&#41; and angiotensin II receptor antagonists &#40;ARA II&#41; to preserve renal function in this group of diseases&#46;<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">28&#44;29</span></a></p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Plasma therapy</span><p id="par0090" class="elsevierStylePara elsevierViewall">Experience with its use is based on individual cases&#44; such as the report by Lich et al&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> of 2 twins diagnosed with DDD and the previously mentioned report by Habbig et al&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> Both cases had factor H deficiency secondary to a mutation and a satisfactory response to factor H repletion achieved using plasma exchange&#46; The direct contribution of this factor could be available for therapeutic use in the near future&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> In other cases&#44; plasmapheresis with replenishment of plasma factors has not been effective&#44; according to the reports by McCaughan et al&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a> and Martinez-Barricarte et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> all of which dealt with DDD&#46; Martinez-Barricarte et al&#46; postulated the presence of a C3 convertase mutation that would make it resistant to the inhibitory action of factor<span class="elsevierStyleHsp" style=""></span>H and would therefore hinder the effectiveness of replenishing plasma factor&#46; This would in turn require new specific treatments aimed at restoring control of C3 convertase activity and eliminating C3 degradation products from plasma&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a></p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Cellular immunosuppression</span><p id="par0095" class="elsevierStylePara elsevierViewall">There is no evidence supporting the use of immunosuppressive therapy in C3 glomerulopathy&#44;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> given that the various lines of treatment have provided highly variable responses and questionable efficacy&#44; as is the case with prednisone and mycophenolate&#44; which have shown no benefit according to the cases reported by Sethi et al&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> and Bomback et al&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a> The combination of these agents with biological therapies&#44; such as the antilymphocyte CD20 monoclonal antibody rituximab used by McCaughan et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a> was also ineffective in a kidney transplant recipient&#46;</p></span></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Eculizumab</span><p id="par0100" class="elsevierStylePara elsevierViewall">Eculizumab is an anti-C5 antibody that impedes the excision of C5 in C5b and decreases the production of C5a&#44; thereby preventing the activation of the terminal cascade and the formation of CAM &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> Eculizumab was the first drug that&#44; using this mechanism of action&#44; managed to effectively and safely reduce hemolysis in paroxysmal nocturnal hemoglobinuria&#46; This condition was the first indication for eculizumab in 2008&#44;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a> although practically every year new applications and therapeutic indications are being discovered for numerous diseases mediated by the complement&#44; such as atypical hemolytic-uremic syndrome&#44;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a> C3 glomerulopathy and HELLP syndrome&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a> The most important secondary effect of eculizumab is a direct consequence of the inhibition of the terminal complement cascade&#44; which predisposes patients to infections by encapsulated germs such as <span class="elsevierStyleItalic">Neisseria meningitidis</span>&#46; Vaccinations and antibiotic prophylaxis are therefore recommended at least 14<span class="elsevierStyleHsp" style=""></span>days before starting treatment with eculizumab&#46;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">36&#44;37</span></a></p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0105" class="elsevierStylePara elsevierViewall">The first published cases of glomerulonephritis treated with eculizumab<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">31&#44;32&#44;38&#8211;41</span></a> appeared in the literature in 2012&#44; 6 of them with DDD&#44; 3 with GNC3 and another diagnosed with MPGN I refractory to treatment&#46; Of the 10 patients who underwent the treatment&#44; improved renal function parameters were observed in 8&#44; with 1 patient showing lower glomerulonephritis activity at the histopathological level in a second biopsy&#46; The 2 remaining patients experienced renal function deterioration during the follow-up&#44; 1 of whom eventually required dialysis&#46; It is worth noting that 2 of the patients who responded positively worsened immediately after the use of eculizumab was withdrawn&#46; An association was found between MAC levels prior to treatment and the response to the same&#59; these levels could therefore be useful as a predictive factor&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Given the high cost of therapy with this antibody&#44; patient candidates for undergoing this therapy should be selected carefully&#46; A recent review by Zuber et al&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">42</span></a> on the use of eculizumab in atypical hemolytic-uremic syndrome and C3 glomerulopathy suggested that optimal candidates for taking eculizumab would be patients with a recent diagnosis&#44; active inflammatory lesions &#40;crescent formation and endocapillary proliferation&#41; and minimal interstitial fibrosis in the pathology&#44; as well as an increase in serum creatinine and&#47;or proteinuria levels and high serum MAC levels &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">32&#44;43</span></a></p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Prognosis</span><p id="par0115" class="elsevierStylePara elsevierViewall">The accumulated experience indicates that the long-term prognosis is poor&#44; given that a high percentage of patients progress to ESRD &#40;approximately 50&#37; of patients with DDD and 15&#8211;20&#37; with GNC3 at 10 years&#41;&#44; which might be due to the lesser aggressiveness of GNC3&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;19&#8211;24&#44;31&#44;32&#44;38&#44;39&#44;41&#44;44&#8211;46</span></a> A possible explanation is the increased prevalence of C3 nephritic factor in DDD &#40;80&#37; vs&#46; 45&#8211;50&#37; in GNC3&#41;&#46; It is clear that more studies and case series are needed to assess the long-term prognosis of this new entity&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Conclusions and recommendations</span><p id="par0120" class="elsevierStylePara elsevierViewall">C3 glomerulopathy is a rare condition with an unfortunate renal prognosis&#44; whose diagnosis is based on the finding of isolated C3 deposits in the renal biopsy&#46; The detection of low plasma levels of complement regulation factors can provide a criterion for selecting the optimal treatment&#46; The rarity of the disease has precluded the availability of strong evidence&#44; and there are only small series of patients in whom different treatment modalities have been employed&#46; Anticomplement therapy with eculizumab has offered the most promising results so far&#44; although it requires a careful selection of candidates&#44; such as those without no chronicity data in the renal biopsy and with renal function impairment and&#47;or proteinuria&#44; as well as high levels of MAC &#40;when their measurement is possible&#41;&#44; because they are associated with a better treatment response&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">In the case of our patient&#44; electron microscopy of the renal biopsy confirmed the diagnosis of C3 glomerulonephritis&#46; A study was performed of the alternative complement pathway&#44; which showed normal levels of factors I and H&#44; with no abnormal bands in the structural characterization of factor H and the absence of antifactor H antibodies and C3 nephritic factor&#46; The genetic study&#44; however&#44; detected a change in heterozygosity in exon 4 of the factor I gene&#46; Based on the test results predicting the functional effects&#44; this change was proposed as benign&#44; although complete functional studies are needed to rule out its association with this disease&#46; Based on these results and confirming that the patient did not meet &#40;at the time of the diagnosis&#41; the recommended requirements for taking eculizumab&#44; treatment was started with an angiotensin-converting enzyme inhibitor at the maximum tolerated dosage&#44; reducing proteinuria by approximately 40&#37; from its maximum value of 6<span class="elsevierStyleHsp" style=""></span>g&#47;day and maintaining normal renal function until now&#46; In the event of renal function deterioration and&#47;or increase in proteinuria despite renin&#8211;angiotensin&#8211;aldosterone system blockade&#44; the experts recommended starting treatment with eculizumab or immunosuppressive therapy with mycophenolate mofetil if eculizumab is not available or if the patient does not clearly meet the criteria for eculizumab&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Conflicts of interest</span><p id="par0130" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
    "textoCompletoSecciones" => array:1 [
      "secciones" => array:14 [
        0 => array:2 [
          "identificador" => "xres343298"
          "titulo" => "Abstract"
        ]
        1 => array:2 [
          "identificador" => "xpalclavsec324878"
          "titulo" => "Keywords"
        ]
        2 => array:2 [
          "identificador" => "xres343297"
          "titulo" => "Resumen"
        ]
        3 => array:2 [
          "identificador" => "xpalclavsec324877"
          "titulo" => "Palabras clave"
        ]
        4 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "The clinical problem"
        ]
        5 => array:3 [
          "identificador" => "sec0010"
          "titulo" => "C3 glomerulopathy"
          "secciones" => array:2 [
            0 => array:2 [
              "identificador" => "sec0015"
              "titulo" => "Dense-deposit disease"
            ]
            1 => array:2 [
              "identificador" => "sec0020"
              "titulo" => "C3 glomerulonephritis"
            ]
          ]
        ]
        6 => array:2 [
          "identificador" => "sec0025"
          "titulo" => "Etiopathogenesis"
        ]
        7 => array:2 [
          "identificador" => "sec0030"
          "titulo" => "Assessment of patients with C3 glomerulopathy"
        ]
        8 => array:3 [
          "identificador" => "sec0035"
          "titulo" => "Treatment"
          "secciones" => array:3 [
            0 => array:2 [
              "identificador" => "sec0040"
              "titulo" => "Renin&#8211;angiotensin axis inhibitors"
            ]
            1 => array:2 [
              "identificador" => "sec0045"
              "titulo" => "Plasma therapy"
            ]
            2 => array:2 [
              "identificador" => "sec0050"
              "titulo" => "Cellular immunosuppression"
            ]
          ]
        ]
        9 => array:2 [
          "identificador" => "sec0055"
          "titulo" => "Eculizumab"
        ]
        10 => array:2 [
          "identificador" => "sec0060"
          "titulo" => "Prognosis"
        ]
        11 => array:2 [
          "identificador" => "sec0065"
          "titulo" => "Conclusions and recommendations"
        ]
        12 => array:2 [
          "identificador" => "sec0070"
          "titulo" => "Conflicts of interest"
        ]
        13 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2013-06-24"
    "fechaAceptado" => "2014-01-20"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec324878"
          "palabras" => array:7 [
            0 => "C3 glomerulopathy"
            1 => "Dense-deposit disease"
            2 => "Alternative complement pathway"
            3 => "Factor H"
            4 => "Factor I"
            5 => "C3 nephritic factor"
            6 => "Eculizumab"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec324877"
          "palabras" => array:7 [
            0 => "Glomerulopat&#237;a C3"
            1 => "Enfermedad por dep&#243;sitos densos"
            2 => "V&#237;a alternativa del complemento"
            3 => "Factor H"
            4 => "Factor I"
            5 => "Factor nefr&#237;tico C3"
            6 => "Eculizumab"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">C3 glomerulopathy is a new&#44; recently described entity that has changed the perspective&#44; treatment and classification of a number of glomerular diseases&#46; It encompasses 2 similar but clearly differentiated pathologies&#8212;the dense-deposit disease and C3 glomerulonephritis itself&#46; The alternative complement pathway plays a fundamental role in its pathogenesis and&#44; specifically&#44; the mutations and defects in its regulatory factors &#40;mainly factor H and factor <span class="elsevierStyleSmallCaps">I</span>&#41;&#44; as well as the presence of acquired autoantibodies &#40;C3 nephritic factor&#41;&#44; which generates an unbridled activation of the system&#44; and ultimately&#44; a deposit of its products at the glomerular level&#46; Its poor prognosis and onset in young populations make the detailed study of new therapeutic alternatives for this disease essential&#46; Recently eculizumab&#44; an anti-C5 antibody&#44; has demonstrated effectiveness in the treatment of these patients&#46;</p>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">La glomerulopat&#237;a C3 es una nueva entidad descrita recientemente que ha cambiado la visi&#243;n&#44; el tratamiento y la clasificaci&#243;n de algunas enfermedades glomerulares&#46; Engloba 2 patolog&#237;as similares pero claramente diferenciadas&#58; la enfermedad por dep&#243;sitos densos y la glomerulonefritis C3 propiamente dicha&#46; La v&#237;a alternativa del complemento juega un papel fundamental en su patogenia&#44; y en concreto las mutaciones o defectos en sus factores reguladores &#40;fundamentalmente factor H y factor <span class="elsevierStyleSmallCaps">I</span>&#41;&#44; as&#237; como la presencia de autoanticuerpos adquiridos &#40;factor nefr&#237;tico C3&#41; que generan una activaci&#243;n desenfrenada del sistema&#44; y en &#250;ltimo t&#233;rmino un dep&#243;sito de sus productos a nivel glomerular&#46; Su mal pron&#243;stico y la aparici&#243;n en poblaci&#243;n joven hacen preciso el estudio de nuevas alternativas terap&#233;uticas&#46; Recientemente eculizumab&#44; un anticuerpo anti C5&#44; ha demostrado efectividad en el tratamiento de estos pacientes&#46;</p>"
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0020">Please cite this article as&#58; de Lorenzo A&#44; Tall&#243;n S&#44; Hern&#225;ndez-Sevillano B&#44; de Arriba G&#46; Glomerulopat&#237;a C3&#58; una nueva entidad basada en el complemento&#46; Rev Clin Esp&#46; 2014&#59;214&#58;266&#8211;274&#46;</p>"
      ]
    ]
    "multimedia" => array:6 [
      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 1362
            "Ancho" => 1652
            "Tamanyo" => 95391
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Alternative complement pathway&#46; In the activation of the alternative complement pathway&#44; C3 convertase cleaves C3 into C3a and C3b&#44; the latter of which is a potent C3 convertase amplifier and generator&#46; This process is regulated by factor H &#40;which inhibits C3 convertase&#41; and factor I &#40;which converts C3b into inactive C3b&#44; thereby slowing the cascade&#41;&#46; In addition&#44; C5 convertase is generated from the products derived from the action of C3 convertase&#46; This enzyme cleaves C5 into C5a and C5b&#46; The binding of C5b with C6&#8211;C9 forms the membrane attack complex &#40;MAC&#41; with chemotactic activity in the cell surfaces&#44; resulting in cell lysis&#46;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "fig0010"
        "etiqueta" => "Figure 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
            "Alto" => 2145
            "Ancho" => 2647
            "Tamanyo" => 318630
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Classification of membranoproliferative glomerulonephritis&#46; <span class="elsevierStyleItalic">Abbreviations</span>&#58; DDD&#44; dense-deposit disease&#59; GNC3&#44; C3 glomerulonephritis&#59; MPGN&#44; membranoproliferative glomerulonephritis&#59; IF&#44; immunofluorescence&#59; electron M&#46;&#44; electron microscope&#59; and GBM&#44; glomerular basement membrane&#46;</p>"
        ]
      ]
      2 => array:7 [
        "identificador" => "fig0015"
        "etiqueta" => "Figure 3"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr3.jpeg"
            "Alto" => 1041
            "Ancho" => 1649
            "Tamanyo" => 109505
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Treatment&#46; Treatment regimen based on the findings of the complement functionality and genetics study&#46; <span class="elsevierStyleItalic">Abbreviations</span>&#58; ARA II&#44; angiotensin II receptor antagonists&#59; and ACEI&#44; angiotensin-converting enzyme inhibitors&#46;</p>"
        ]
      ]
      3 => array:7 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Membranoproliferative glomerulonephritis mediated by immune complexes is produced by persistent antigenemia whose resulting immune complex activates the classical complement pathway&#46; Direct immunofluorescence stainings will be positive to immunoglobulins&#44; mainly IgG and IgM&#44; as well as C3 and&#47;or C1&#46; C3 glomerulopathy is produced by dysfunction of the alternative complement pathway &#40;mutations or autoantibodies&#41;&#59; its direct immunofluorescence is negative for immunoglobulins but positive for complement &#40;C3&#41;&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Mediated by immune complexes</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Infections&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Autoimmune diseases&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Neoplasms&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Gammopathies&#47;dysproteinemias&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Mediated by complement&#58; C3 glomerulopathy</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Dense-deposit disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>C3 glomerulonephritis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab509738.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">New classification of membranoproliferative glomerulonephritis&#46;</p>"
        ]
      ]
      4 => array:7 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:3 [
          "leyenda" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Alb&#44; plasma albumin&#59; CFM&#44; cyclophosphamide&#59; Cr&#44; plasma creatinine&#59; E&#44; steroids&#59; DDD&#44; dense-deposit disease&#59; ESRD&#44; end-stage renal disease&#59; RF&#44; renal function&#59; Glom&#46;C3&#44; glomerulopathy C3&#59; GNC3&#44; glomerulonephritis C3&#59; RAASI&#44; renin&#8211;angiotensin&#8211;aldosterone system inhibitors&#59; MMF&#44; mycophenolate mofetil&#59; N&#44; native kidney&#59; ND&#44; not described&#59; MCP&#44; membrane cofactor protein&#59; Pr&#44; proteinuria&#59; and T&#44; kidney transplant&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Author&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">n</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Diagnosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Mutation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">C3 nephritic factor&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Native kidney&#47;transplant&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Response&#47;evolution&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Servais et al&#46; &#40;2007&#41;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">GNC3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Factor H &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&#41;Factor I &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#41;MCP &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Positive &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">RAASI &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>8&#41;E &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">RF impairment &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>15&#41;&#44; of these ESRDs &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Habbig et al&#46; &#40;2009&#41;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">GNC3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Factor H &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fresh plasma infusion&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No disease progression&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mart&#237;nez-Barricarte et al&#46; &#40;2010&#41;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">DDD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#41;T &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Darouich et al&#46; &#40;2011&#41;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">44</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">GNC3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Gale et al&#46; &#40;2010&#41;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a>Athanasiou et al&#46; &#40;2011&#41;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a>Deltas et al&#46; &#40;2013&#41;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">45</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">136&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Glom&#46;C3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Factor H &#40;CFHR5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Negative &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>4&#41;<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">RF deterioration to ESRD &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>28&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sugimoto et al&#46; &#40;2012&#41;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">46</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">GNC3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Factor H&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">RAASI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No RF impairment Increased Pr&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sethi et al&#46; &#40;2012&#41;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">GNC3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Factor H &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#41;Factor I &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Positive &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>10&#41;T &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">RAASI &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#41;RAASI<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>E &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>7&#41;MMF &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&#41;E<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>CFM &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No RF impairment &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>10&#41;&#46; No response &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Servais et al&#46; &#40;2012&#41;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">85&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">GNC3 &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>56&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Factor H &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>7&#41;Factor I &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&#41;MCP &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Positive &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>24&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N and T &#40;number not specified&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">RAASI &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>19&#41;IS &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>19&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">RF deterioration to ESRD &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>27&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">DDD &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>29&#41;<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Factor H &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Positive &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>19&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">RAASI &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>14&#41;IS &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>14&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">RF deterioration to ESRD &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>23&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">McCaughan et al&#46; &#40;2012&#41;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">DDD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">T&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Eculizumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Reduction of Cr and Pr&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Bomback et al&#46; &#40;2012&#41;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">GNC3 &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&#41;DDD &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Factor H &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#41;MCP &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Positive &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&#41;T &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Eculizumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Reduction of Cr &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#41; and Pr &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#41;&#46; Increase of Alb &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Vivarelli et al&#46; &#40;2012&#41;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">DDD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Eculizumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Reduction of Pr Increase of Alb&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Daina et al&#46; &#40;2012&#41;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">39</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">DDD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Eculizumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Reduction of Cr and Pr Increase of Alb&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Gurkan et al&#46; &#40;2013&#41;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">GNC3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">T&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Eculizumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Stable Cr and Pr Histopathologic progression&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab509737.png"
              ]
            ]
          ]
          "notaPie" => array:2 [
            0 => array:3 [
              "identificador" => "tblfn0005"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Measurement performed in 4 patients&#46;</p>"
            ]
            1 => array:3 [
              "identificador" => "tblfn0010"
              "etiqueta" => "b"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0010">The total number of patients in the series is complete with 41 patients who were diagnosed with type I membranoproliferative glomerulonephritis&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Case series of C3 glomerulopathy&#58; characteristics&#44; treatment and evolution&#46;</p>"
        ]
      ]
      5 => array:7 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:3 [
          "leyenda" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Standard dosage for patients older than 18 years&#58; 900<span class="elsevierStyleHsp" style=""></span>mg weekly for the first 4 weeks&#44; followed by 1200<span class="elsevierStyleHsp" style=""></span>mg on the fifth week and subsequent maintenance with 1200<span class="elsevierStyleHsp" style=""></span>mg every 2 weeks&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Weight&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Induction&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Administration<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Maintenance&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Administration<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#62;40<span class="elsevierStyleHsp" style=""></span>kg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">900<span class="elsevierStyleHsp" style=""></span>mg&#47;week&#59; 4<span class="elsevierStyleHsp" style=""></span>dose&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">180<span class="elsevierStyleHsp" style=""></span>mL in 30&#8211;45<span class="elsevierStyleHsp" style=""></span>min&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1200<span class="elsevierStyleHsp" style=""></span>mg every 2<span class="elsevierStyleHsp" style=""></span>weeks&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">240<span class="elsevierStyleHsp" style=""></span>mL in 30&#8211;45<span class="elsevierStyleHsp" style=""></span>min&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30&#8211;40<span class="elsevierStyleHsp" style=""></span>kg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">600<span class="elsevierStyleHsp" style=""></span>mg&#47;week&#59; 2<span class="elsevierStyleHsp" style=""></span>dose&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">120<span class="elsevierStyleHsp" style=""></span>mL in 30&#8211;45<span class="elsevierStyleHsp" style=""></span>min&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">900<span class="elsevierStyleHsp" style=""></span>mg every 2<span class="elsevierStyleHsp" style=""></span>weeks&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">180<span class="elsevierStyleHsp" style=""></span>mL in 30&#8211;45<span class="elsevierStyleHsp" style=""></span>min&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20&#8211;30<span class="elsevierStyleHsp" style=""></span>kg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">600<span class="elsevierStyleHsp" style=""></span>mg&#47;week&#59; 2<span class="elsevierStyleHsp" style=""></span>dose&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">120<span class="elsevierStyleHsp" style=""></span>mL in 30&#8211;45<span class="elsevierStyleHsp" style=""></span>min&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">600<span class="elsevierStyleHsp" style=""></span>mg every 2<span class="elsevierStyleHsp" style=""></span>weeks&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">120<span class="elsevierStyleHsp" style=""></span>mL in 30&#8211;45<span class="elsevierStyleHsp" style=""></span>min&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&#8211;20<span class="elsevierStyleHsp" style=""></span>kg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">600<span class="elsevierStyleHsp" style=""></span>mg single dose&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">120<span class="elsevierStyleHsp" style=""></span>mL in 30&#8211;45<span class="elsevierStyleHsp" style=""></span>min&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">300<span class="elsevierStyleHsp" style=""></span>mg every 2<span class="elsevierStyleHsp" style=""></span>weeks&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">60<span class="elsevierStyleHsp" style=""></span>mL in 30&#8211;45<span class="elsevierStyleHsp" style=""></span>min&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#8211;10<span class="elsevierStyleHsp" style=""></span>kg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">300<span class="elsevierStyleHsp" style=""></span>mg single dose&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">60<span class="elsevierStyleHsp" style=""></span>mL in 30&#8211;45<span class="elsevierStyleHsp" style=""></span>min&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">300<span class="elsevierStyleHsp" style=""></span>mg every 2<span class="elsevierStyleHsp" style=""></span>weeks&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">60<span class="elsevierStyleHsp" style=""></span>mL in 30&#8211;45<span class="elsevierStyleHsp" style=""></span>min&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab509739.png"
              ]
            ]
          ]
          "notaPie" => array:1 [
            0 => array:3 [
              "identificador" => "tblfn0015"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0015">300<span class="elsevierStyleHsp" style=""></span>mg vials &#40;30<span class="elsevierStyleHsp" style=""></span>mL&#41; in dilution 5<span class="elsevierStyleHsp" style=""></span>mg&#47;mL with physiological saline &#40;0&#46;9&#37;&#44; 0&#46;45&#37;&#41; or glucose solution &#40;5&#37;&#41;&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Eculizumab&#58; dosage and method of administration&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:46 [
            0 => array:3 [
              "identificador" => "bib0005"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Primary glomerulonephritis with isolated C3 deposits&#58; a new entity which shares common genetic risk factors with haemolytic uraemic syndrome"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46; Servais"
                            1 => "V&#46; Fremeaux-Bacchi"
                            2 => "M&#46; Lequintrec"
                            3 => "R&#46; Salomon"
                            4 => "J&#46; Blouin"
                            5 => "J&#46; Knebelmann"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/jmg.2006.045328"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Med Genet"
                        "fecha" => "2007"
                        "volumen" => "44"
                        "paginaInicial" => "193"
                        "paginaFinal" => "199"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17018561"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0010"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "C3 glomerulopathy&#58; a new classification"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "F&#46; Fakhouri"
                            1 => "V&#46; Fremeaux-Bacchi"
                            2 => "L-H&#46; Noel"
                            3 => "H&#46;T&#46; Cook"
                            4 => "M&#46;C&#46; Pickering"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/nrneph.2010.85"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nat Rev Nephrol"
                        "fecha" => "2010"
                        "volumen" => "6"
                        "paginaInicial" => "494"
                        "paginaFinal" => "499"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20606628"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0015"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Membranoproliferative glomerulonephritis type II &#40;dense deposit disease&#41;&#58; an update"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "G&#46;B&#46; Appel"
                            1 => "H&#46;T&#46; Cook"
                            2 => "G&#46; Hageman"
                            3 => "J&#46;C&#46; Jennette"
                            4 => "M&#46; Kashgarian"
                            5 => "M&#46; Kirschfink"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1681/ASN.2005010078"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Am Soc Nephrol"
                        "fecha" => "2005"
                        "volumen" => "16"
                        "paginaInicial" => "1392"
                        "paginaFinal" => "1403"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15800116"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0020"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The amplification loop of the complement pathways"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "P&#46;J&#46; Lachmann"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S0065-2776(08)04004-2"
                      "Revista" => array:6 [
                        "tituloSerie" => "Adv Immunol"
                        "fecha" => "2009"
                        "volumen" => "104"
                        "paginaInicial" => "115"
                        "paginaFinal" => "149"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20457117"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0025"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Dense deposit disease&#58; clinicopathologic study of 32 pediatric and adult patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46;H&#46; Nasr"
                            1 => "A&#46;M&#46; Valeri"
                            2 => "G&#46;B&#46; Appel"
                            3 => "J&#46; Sherwinter"
                            4 => "M&#46;B&#46; Stokes"
                            5 => "S&#46;M&#46; Said"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.2215/CJN.03480708"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin J Am Soc Nephrol"
                        "fecha" => "2009"
                        "volumen" => "4"
                        "paginaInicial" => "22"
                        "paginaFinal" => "32"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18971369"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0030"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Dense Deposit Disease Focus Group&#58; new approaches to the treatment of dense deposit disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "R&#46;J&#46;H&#46; Smith"
                            1 => "J&#46; Alexander"
                            2 => "P&#46;N&#46; Barlow"
                            3 => "M&#46; Botto"
                            4 => "T&#46;L&#46; Cassavant"
                            5 => "H&#46;T&#46; Cook"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1681/ASN.2007030356"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Am Soc Nephrol"
                        "fecha" => "2007"
                        "volumen" => "18"
                        "paginaInicial" => "2447"
                        "paginaFinal" => "2456"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17675665"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0035"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Proliferative glomerulonephritis secondary to dysfunction of the alternative pathway of complement"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46; Sethi"
                            1 => "F&#46;C&#46; Fervenza"
                            2 => "Y&#46; Zhang"
                            3 => "S&#46;H&#46; Nasr"
                            4 => "N&#46; Leung"
                            5 => "J&#46; Vrana"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "J Am Soc Nephrol"
                        "fecha" => "2011"
                        "volumen" => "6"
                        "paginaInicial" => "1009"
                        "paginaFinal" => "1017"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0040"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cryoglobulinemia and renal disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "C&#46;E&#46; Alpers"
                            1 => "K&#46;D&#46; Smith"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/MNH.0b013e3282f8afe2"
                      "Revista" => array:6 [
                        "tituloSerie" => "Curr Opin Nephrol Hypertens"
                        "fecha" => "2008"
                        "volumen" => "17"
                        "paginaInicial" => "243"
                        "paginaFinal" => "249"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18408474"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib0045"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The role of complement in cryoglobulin-induced immune complex glomerulonephritis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Trendelenburg"
                            1 => "L&#46; Fossati-Jimack"
                            2 => "J&#46; Cortes-Hernandez"
                            3 => "D&#46; Turnberg"
                            4 => "M&#46; Lewis"
                            5 => "S&#46; Izui"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Immunol"
                        "fecha" => "2005"
                        "volumen" => "175"
                        "paginaInicial" => "6909"
                        "paginaFinal" => "6914"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16272350"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0050"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hepatitis C virus infection and membranoproliferative glomerulonephritis in Japan"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "H&#46; Yamabe"
                            1 => "R&#46;J&#46; Johnson"
                            2 => "D&#46;R&#46; Gretch"
                            3 => "K&#46; Fukushi"
                            4 => "H&#46; Osawa"
                            5 => "M&#46; Miyata"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Am Soc Nephrol"
                        "fecha" => "1995"
                        "volumen" => "6"
                        "paginaInicial" => "220"
                        "paginaFinal" => "223"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7579088"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib0055"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "New approaches to the treatment of dense deposit disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "R&#46;J&#46;H&#46; Smith"
                            1 => "J&#46; Alexander"
                            2 => "P&#46;N&#46; Barlow"
                            3 => "M&#46; Botto"
                            4 => "T&#46;L&#46; Cassavant"
                            5 => "H&#46;T&#46; Cook"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1681/ASN.2007030356"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Am Soc Nephrol"
                        "fecha" => "2007"
                        "volumen" => "18"
                        "paginaInicial" => "2447"
                        "paginaFinal" => "2456"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17675665"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib0060"
              "etiqueta" => "12"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Idiopathic mesangiocapillary glomerulonephritis&#58; comparison of types I and II in children and adults and long-term prognosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46;S&#46; Cameron"
                            1 => "D&#46;R&#46; Turner"
                            2 => "J&#46; Heaton"
                            3 => "D&#46;G&#46; Williams"
                            4 => "C&#46;S&#46; Ogg"
                            5 => "C&#46; Chantler"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Med"
                        "fecha" => "1983"
                        "volumen" => "74"
                        "paginaInicial" => "175"
                        "paginaFinal" => "192"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/6337487"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib0065"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Idiopathic membranoproliferative glomerulonephritis in childhood"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "C&#46;D&#46; West"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Pediatr Nephrol"
                        "fecha" => "1992"
                        "volumen" => "6"
                        "paginaInicial" => "96"
                        "paginaFinal" => "103"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1536750"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib0070"
              "etiqueta" => "14"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The complement system in regulation of adaptive immunity"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "M&#46;C&#46; Carroll"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/ni1113"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nat Immunol"
                        "fecha" => "2004"
                        "volumen" => "5"
                        "paginaInicial" => "981"
                        "paginaFinal" => "986"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15454921"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib0075"
              "etiqueta" => "15"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "C3 glomerulopathy masquerading as acute postinfectious glomerulonephritis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "G&#46; Sandhu"
                            1 => "A&#46; Bansal"
                            2 => "A&#46; Ranade"
                            3 => "J&#46; Jones"
                            4 => "S&#46; Cortell"
                            5 => "G&#46;S&#46; Markowitz"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1053/j.ajkd.2012.04.032"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Kidney Dis"
                        "fecha" => "2012"
                        "volumen" => "60"
                        "paginaInicial" => "1039"
                        "paginaFinal" => "1043"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22770945"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib0080"
              "etiqueta" => "16"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "H deficiency in two brothers with atypical dense intramembranous deposit disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Levy"
                            1 => "L&#46; Halbwachs-Mecarelli"
                            2 => "M-C&#46; Gubler"
                            3 => "G&#46; Kohout"
                            4 => "A&#46; Bensenouci"
                            5 => "P&#46; Niaudet"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Kidney Int"
                        "fecha" => "1986"
                        "volumen" => "30"
                        "paginaInicial" => "949"
                        "paginaFinal" => "956"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2950269"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib0085"
              "etiqueta" => "17"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Heterozygous and homozygous factor H deficiencies associated with hemolytic uremic syndrome or membranoproliferative glomerulonephritis&#58; report and genetic analysis of 16 cases"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46;A&#46; Dragon-Durey"
                            1 => "V&#46; Fremeaux-Bacchi"
                            2 => "C&#46; Loirat"
                            3 => "J&#46; Blouin"
                            4 => "P&#46; Niaudet"
                            5 => "G&#46; Deschenes"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Am Soc Nephrol"
                        "fecha" => "2004"
                        "volumen" => "15"
                        "paginaInicial" => "787"
                        "paginaFinal" => "795"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14978182"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib0090"
              "etiqueta" => "18"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Deletion of Lys224 in regulatory domain 4 of factor H reveals a novel pathomechanism for dense deposit disease &#40;MPGN II&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "C&#46; Licht"
                            1 => "S&#46; Heinen"
                            2 => "M&#46; Jozsi"
                            3 => "I&#46; L&#246;schmann"
                            4 => "R&#46;E&#46; Saunders"
                            5 => "S&#46;J&#46; Perkins"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/sj.ki.5000269"
                      "Revista" => array:6 [
                        "tituloSerie" => "Kidney Int"
                        "fecha" => "2006"
                        "volumen" => "70"
                        "paginaInicial" => "42"
                        "paginaFinal" => "50"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16612335"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib0095"
              "etiqueta" => "19"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Human C3 mutation reveals a mechanism of dense deposit disease pathogenesis and provides insights into complement activation and regulation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "R&#46; Martinez-Barricarte"
                            1 => "M&#46; Heurich"
                            2 => "F&#46; Valdes-Canedo"
                            3 => "E&#46; Vazquez-Martul"
                            4 => "E&#46; Torreira"
                            5 => "T&#46; Montes"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1172/JCI43343"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Invest"
                        "fecha" => "2010"
                        "volumen" => "120"
                        "paginaInicial" => "3702"
                        "paginaFinal" => "3712"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20852386"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib0100"
              "etiqueta" => "20"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "C3 glomerulonephritis&#58; clinicopathologic findings&#44; complement abnormalities&#44; glomerular proteomic profile&#44; treatment and followup"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46; Sethi"
                            1 => "F&#46;C&#46; Fervenza"
                            2 => "Y&#46; Zhang"
                            3 => "L&#46; Zand"
                            4 => "J&#46;A&#46; Vrana"
                            5 => "S&#46;H&#46; Nasr"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/ki.2012.212"
                      "Revista" => array:6 [
                        "tituloSerie" => "Kidney Int"
                        "fecha" => "2012"
                        "volumen" => "82"
                        "paginaInicial" => "465"
                        "paginaFinal" => "473"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22673887"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib0105"
              "etiqueta" => "21"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Complement factor H-related protein 5 &#40;CFHR5&#41; nephropathy&#58; an endemic cause of renal disease in Cyprus"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "D&#46;P&#46; Gale"
                            1 => "E&#46;G&#46; de Jorge"
                            2 => "H&#46;T&#46; Cook"
                            3 => "R&#46; Martinez-Barricarte"
                            4 => "A&#46; Hadjisavvas"
                            5 => "G&#46; Adam"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S0140-6736(10)60670-8"
                      "Revista" => array:7 [
                        "tituloSerie" => "Lancet"
                        "fecha" => "2010"
                        "volumen" => "376"
                        "paginaInicial" => "794"
                        "paginaFinal" => "801"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20800271"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S000293780200087X"
                          "estado" => "S300"
                          "issn" => "00029378"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib0110"
              "etiqueta" => "22"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Familial C3 glomerulopathy associated with CFHR5 mutations&#58; Clinical characteristics of 91 patients in 16 pedigrees"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "Y&#46; Athanasiou"
                            1 => "K&#46; Voskarides"
                            2 => "D&#46;P&#46; Gale"
                            3 => "L&#46; Damianou"
                            4 => "C&#46; Patsias"
                            5 => "M&#46; Zavros"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.2215/CJN.09541010"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin J Am Soc Nephrol"
                        "fecha" => "2011"
                        "volumen" => "6"
                        "paginaInicial" => "1436"
                        "paginaFinal" => "1446"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21566112"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib0115"
              "etiqueta" => "23"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Acquired and genetic complement abnormalities play a critical role in dense deposit disease and other C3 glomerulopathies"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46; Servais"
                            1 => "L&#46;H&#46; Noel"
                            2 => "L&#46;T&#46; Roumenina"
                            3 => "M&#46; le Quintrec"
                            4 => "S&#46; Ngo"
                            5 => "M&#46;A&#46; Dragon-Durey"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/ki.2012.63"
                      "Revista" => array:6 [
                        "tituloSerie" => "Kidney Int"
                        "fecha" => "2012"
                        "volumen" => "82"
                        "paginaInicial" => "454"
                        "paginaFinal" => "464"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22456601"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib0120"
              "etiqueta" => "24"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "C3 deposition glomerulopathy due to a functional factor H defect"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46; Habbig"
                            1 => "M&#46;J&#46; Mihatsch"
                            2 => "S&#46; Heinen"
                            3 => "B&#46; Beck"
                            4 => "M&#46; Emmel"
                            5 => "C&#46; Skerka"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/ki.2008.354"
                      "Revista" => array:6 [
                        "tituloSerie" => "Kidney Int"
                        "fecha" => "2009"
                        "volumen" => "75"
                        "paginaInicial" => "1230"
                        "paginaFinal" => "1234"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18633337"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            24 => array:3 [
              "identificador" => "bib0125"
              "etiqueta" => "25"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Human C3 mutation reveals a mechanism of dense deposit disease pathogenesis and provides insights into complement activation and regulation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "R&#46; Mart&#237;nez-Barricarte"
                            1 => "M&#46; Heurich"
                            2 => "F&#46; Valdes-Ca&#241;edo"
                            3 => "E&#46; Vazquez-Martul"
                            4 => "E&#46; Torreira"
                            5 => "T&#46; Montes"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1172/JCI43343"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Invest"
                        "fecha" => "2010"
                        "volumen" => "120"
                        "paginaInicial" => "3702"
                        "paginaFinal" => "3712"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20852386"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            25 => array:3 [
              "identificador" => "bib0130"
              "etiqueta" => "26"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Pathogenesis of the C3 glomerulopathies and reclassification of MPGN"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "A&#46; Bomback"
                            1 => "G&#46;B&#46; Appel"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/nrneph.2012.213"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nat Rev Nephrol"
                        "fecha" => "2012"
                        "volumen" => "8"
                        "paginaInicial" => "634"
                        "paginaFinal" => "642"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23026947"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            26 => array:3 [
              "identificador" => "bib0135"
              "etiqueta" => "27"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Causes of alternative pathway dysregulation in dense deposit disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "Y&#46; Zhang"
                            1 => "N&#46;C&#46; Meyer"
                            2 => "K&#46; Wang"
                            3 => "C&#46; Nishimura"
                            4 => "K&#46; Frees"
                            5 => "M&#46; Jones"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.2215/CJN.07900811"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin J Am Soc Nephrol"
                        "fecha" => "2012"
                        "volumen" => "7"
                        "paginaInicial" => "265"
                        "paginaFinal" => "274"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22223606"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            27 => array:3 [
              "identificador" => "bib0140"
              "etiqueta" => "28"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The losartan renal protection study&#8212;rationale&#44; study design and baseline characteristics of RENAAL &#40;Reduction of endpoints in NIDDM with the angiotensin II antagonist losartan&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "B&#46;M&#46; Brenner"
                            1 => "M&#46;E&#46; Cooper"
                            2 => "D&#46; de Zeeuw"
                            3 => "J&#46;P&#46; Grunfeld"
                            4 => "W&#46;F&#46; Keane"
                            5 => "K&#46; Kurokawa"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3317/jraas.2000.062"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Renin Angiotensin Aldosterone Syst"
                        "fecha" => "2000"
                        "volumen" => "1"
                        "paginaInicial" => "328"
                        "paginaFinal" => "335"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11967819"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            28 => array:3 [
              "identificador" => "bib0145"
              "etiqueta" => "29"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Renoprotective properties of ACE-inhibition in nondiabetic nephropathies with nonnephrotic proteinuria"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "P&#46; Ruggenenti"
                            1 => "A&#46; Perna"
                            2 => "G&#46; Gherardi"
                            3 => "G&#46; Garini"
                            4 => "C&#46; Zoccali"
                            5 => "M&#46; Salvadori"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S0140-6736(98)10363-X"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet"
                        "fecha" => "1999"
                        "volumen" => "354"
                        "paginaInicial" => "359"
                        "paginaFinal" => "364"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10437863"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            29 => array:3 [
              "identificador" => "bib0150"
              "etiqueta" => "30"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Production of biologically active complement factor H in therapeutically useful quantities"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "C&#46;Q&#46; Schmidt"
                            1 => "F&#46;C&#46; Slingsby"
                            2 => "A&#46; Richards"
                            3 => "P&#46;N&#46; Barlow"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.pep.2010.12.002"
                      "Revista" => array:6 [
                        "tituloSerie" => "Protein Expr Purif"
                        "fecha" => "2011"
                        "volumen" => "76"
                        "paginaInicial" => "254"
                        "paginaFinal" => "263"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21146613"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            30 => array:3 [
              "identificador" => "bib0155"
              "etiqueta" => "31"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Recurrent dense deposit disease after renal transplantation&#58; an emerging role for complementary therapies"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "J&#46;A&#46; McCaughan"
                            1 => "D&#46;M&#46; O&#8217;Rourke"
                            2 => "A&#46;E&#46; Courtney"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1600-6143.2011.03923.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Transplant"
                        "fecha" => "2012"
                        "volumen" => "12"
                        "paginaInicial" => "1046"
                        "paginaFinal" => "1051"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22233157"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            31 => array:3 [
              "identificador" => "bib0160"
              "etiqueta" => "32"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Eculizumab for dense deposit disease and C3 glomerulonephritis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46;S&#46; Bomback"
                            1 => "R&#46;J&#46; Smith"
                            2 => "G&#46;R&#46; Barile"
                            3 => "Y&#46; Zhang"
                            4 => "E&#46;C&#46; Heher"
                            5 => "L&#46; Herlitz"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.2215/CJN.12901211"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin J Am Soc Nephrol"
                        "fecha" => "2012"
                        "volumen" => "7"
                        "paginaInicial" => "748"
                        "paginaFinal" => "756"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22403278"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            32 => array:3 [
              "identificador" => "bib0165"
              "etiqueta" => "33"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Multicenter phase 3 study of the complement inhibitor eculizumab for the treatment of patients with paroxysmal nocturnal hemoglobinuria"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "R&#46;A&#46; Brodsky"
                            1 => "N&#46;S&#46; Young"
                            2 => "E&#46; Antonioli"
                            3 => "A&#46;M&#46; Risitano"
                            4 => "H&#46; Schrezenmeier"
                            5 => "J&#46; Schubert"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1182/blood-2007-06-094136"
                      "Revista" => array:6 [
                        "tituloSerie" => "Blood"
                        "fecha" => "2008"
                        "volumen" => "111"
                        "paginaInicial" => "1840"
                        "paginaFinal" => "1847"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18055865"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            33 => array:3 [
              "identificador" => "bib0170"
              "etiqueta" => "34"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Eculizumab in the treatment of atypical hemolytic uremic syndrome in infants"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "G&#46; Ariceta"
                            1 => "B&#46; Arrizabalaga"
                            2 => "M&#46; Aguirre"
                            3 => "E&#46; Morteruel"
                            4 => "M&#46; Lopez-Trascasa"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1053/j.ajkd.2011.11.027"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Kidney Dis"
                        "fecha" => "2012"
                        "volumen" => "59"
                        "paginaInicial" => "707"
                        "paginaFinal" => "710"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22196848"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            34 => array:3 [
              "identificador" => "bib0175"
              "etiqueta" => "35"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Eculizumab for the treatment of preeclampsia&#47;HELLP syndrome"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "R&#46;M&#46; Burwick"
                            1 => "B&#46;B&#46; Feinberg"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.placenta.2012.11.014"
                      "Revista" => array:6 [
                        "tituloSerie" => "Placenta"
                        "fecha" => "2013"
                        "volumen" => "34"
                        "paginaInicial" => "201"
                        "paginaFinal" => "203"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23228435"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            35 => array:3 [
              "identificador" => "bib0180"
              "etiqueta" => "36"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Combined complete C5 and partial C4 deficiency in humans&#58; clinical consequences and complement-mediated functions in vitro"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "A&#46; Gianella-Borradori"
                            1 => "L&#46; Borradori"
                            2 => "P&#46;M&#46; Schneider"
                            3 => "E&#46; Gautier"
                            4 => "P&#46;J&#46; Sp&#228;th"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Immunol Immunopathol"
                        "fecha" => "1990"
                        "volumen" => "55"
                        "paginaInicial" => "41"
                        "paginaFinal" => "55"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2306879"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            36 => array:3 [
              "identificador" => "bib0185"
              "etiqueta" => "37"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Insufficient protection by <span class="elsevierStyleItalic">Neisseria meningitidis</span> vaccination alone during eculizumab therapy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "A&#46; Bouts"
                            1 => "L&#46; Monnens"
                            2 => "J&#46;C&#46; Davin"
                            3 => "G&#46; Struijk"
                            4 => "L&#46; Spanjaard"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s00467-011-1929-3"
                      "Revista" => array:6 [
                        "tituloSerie" => "Pediatr Nephrol"
                        "fecha" => "2011"
                        "volumen" => "26"
                        "paginaInicial" => "1919"
                        "paginaFinal" => "1920"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21643943"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            37 => array:3 [
              "identificador" => "bib0190"
              "etiqueta" => "38"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Eculizumab for the treatment of densedeposit disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "M&#46; Vivarelli"
                            1 => "A&#46; Pasini"
                            2 => "F&#46; Emma"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMc1111953"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2012"
                        "volumen" => "366"
                        "paginaInicial" => "1163"
                        "paginaFinal" => "1165"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22435383"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            38 => array:3 [
              "identificador" => "bib0195"
              "etiqueta" => "39"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Eculizumab in a patient with dense-deposit disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "E&#46; Daina"
                            1 => "M&#46; Noris"
                            2 => "G&#46; Remuzzi"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMc1112273"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2012"
                        "volumen" => "366"
                        "paginaInicial" => "1161"
                        "paginaFinal" => "1163"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22435382"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            39 => array:3 [
              "identificador" => "bib0200"
              "etiqueta" => "40"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Eculizumab and refractory membranoproliferative glomerulonephritis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46; Radhakrishnan"
                            1 => "A&#46; Lunn"
                            2 => "M&#46; Kirschfink"
                            3 => "P&#46; Thorner"
                            4 => "D&#46; Hebert"
                            5 => "V&#46; Langlois"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMc1106619"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2012"
                        "volumen" => "366"
                        "paginaInicial" => "1165"
                        "paginaFinal" => "1166"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22435384"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            40 => array:3 [
              "identificador" => "bib0205"
              "etiqueta" => "41"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Eculizumab and recurrent C3 glomerulonephritis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "S&#46; Gurkan"
                            1 => "B&#46; Fyfe"
                            2 => "L&#46; Weiss"
                            3 => "X&#46; Xiao"
                            4 => "Y&#46; Zhang"
                            5 => "R&#46;J&#46; Smith"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s00467-013-2503-y"
                      "Revista" => array:6 [
                        "tituloSerie" => "Pediatr Nephrol"
                        "fecha" => "2013"
                        "volumen" => "28"
                        "paginaInicial" => "1975"
                        "paginaFinal" => "1981"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23689905"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            41 => array:3 [
              "identificador" => "bib0210"
              "etiqueta" => "42"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Use of eculizumab for atypical haemolytic uraemic syndrome and C3 glomerulopathies"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "J&#46; Zuber"
                            1 => "F&#46; Fakhouri"
                            2 => "L&#46; Roumenina"
                            3 => "C&#46; Loirat"
                            4 => "V&#46; Fr&#233;meaux-Bacchi"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/nrneph.2012.214"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nat Rev Nephrol"
                        "fecha" => "2012"
                        "volumen" => "8"
                        "paginaInicial" => "643"
                        "paginaFinal" => "657"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23026949"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            42 => array:3 [
              "identificador" => "bib0215"
              "etiqueta" => "43"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Glomerulopat&#237;as C3&#46; Una nueva perspectiva en enfermedades glomerulares"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "C&#46; Rabasco-Ruiz"
                            1 => "A&#46; Huerta-Arroyo"
                            2 => "J&#46; Caro-Espada"
                            3 => "E&#46; Guti&#233;rrez-Mart&#237;nez"
                            4 => "M&#46; Praga-Terente"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3265/Nefrologia.pre2012.Nov.11802"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nefrologia"
                        "fecha" => "2013"
                        "volumen" => "33"
                        "paginaInicial" => "164"
                        "paginaFinal" => "170"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23511752"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            43 => array:3 [
              "identificador" => "bib0220"
              "etiqueta" => "44"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Membranoproliferative glomerulonephritis with isolated C3 deposits&#58; case report and literature review"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "S&#46; Darouich"
                            1 => "R&#46; Goucha"
                            2 => "M&#46;H&#46; Jaafoura"
                            3 => "S&#46; Zekri"
                            4 => "A&#46; Kheder"
                            5 => "H&#46; Ben Maiz"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3109/01913123.2010.532902"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ultrastruct Pathol"
                        "fecha" => "2011"
                        "volumen" => "35"
                        "paginaInicial" => "42"
                        "paginaFinal" => "46"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21265634"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            44 => array:3 [
              "identificador" => "bib0225"
              "etiqueta" => "45"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "C3 glomerulonephritis&#47;CFHR5 nephropathy is an endemic disease in Cyprus&#58; clinical and molecular findings in 21 families"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "C&#46; Deltas"
                            1 => "D&#46; Gale"
                            2 => "T&#46; Cook"
                            3 => "K&#46; Voskarides"
                            4 => "Y&#46; Athanasiou"
                            5 => "A&#46; Pierides"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Adv Exp Med Biol"
                        "fecha" => "2013"
                        "volumen" => "735"
                        "paginaInicial" => "189"
                        "paginaFinal" => "196"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23402027"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            45 => array:3 [
              "identificador" => "bib0230"
              "etiqueta" => "46"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "C3 glomerulonephritis associated with a missense mutation in the factor H gene"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "K&#46; Sugimoto"
                            1 => "S&#46; Fujita"
                            2 => "K&#46; Miyazaki"
                            3 => "M&#46; Okada"
                            4 => "T&#46; Takemura"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Tohoku J Exp Med"
                        "fecha" => "2012"
                        "volumen" => "227"
                        "paginaInicial" => "211"
                        "paginaFinal" => "215"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22790979"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
          ]
        ]
      ]
    ]
  ]
  "idiomaDefecto" => "en"
  "url" => "/22548874/0000021400000005/v1_201406010020/S2254887414000344/v1_201406010020/en/main.assets"
  "Apartado" => array:4 [
    "identificador" => "1904"
    "tipo" => "SECCION"
    "en" => array:2 [
      "titulo" => "Clinical Up-Date"
      "idiomaDefecto" => true
    ]
    "idiomaDefecto" => "en"
  ]
  "PDF" => "https://static.elsevier.es/multimedia/22548874/0000021400000005/v1_201406010020/S2254887414000344/v1_201406010020/en/main.pdf?idApp=WRCEE&text.app=https://revclinesp.es/"
  "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2254887414000344?idApp=WRCEE"
]

Article information

ISSN: 22548874
Original language: English

DOI:10.1016/j.rceng.2014.01.009

The statistics are updated each day

Year/Month	Html	Pdf	Total

2023 March	5	4	9
2018 February	45	0	45
2018 January	45	0	45
2017 December	59	0	59
2017 November	63	0	63
2017 October	43	2	45
2017 September	31	0	31
2017 August	28	0	28
2017 July	26	0	26
2017 June	34	0	34
2017 May	55	0	55
2017 April	43	0	43
2017 March	42	0	42
2017 February	141	0	141
2017 January	36	0	36
2016 December	36	0	36
2016 November	42	0	42
2016 October	79	0	79
2016 September	112	0	112
2016 August	26	0	26
2016 July	4	0	4

Show all

Indexed in:

Follow us:

Subscribe:

Statistics

Indexed in:

Follow us:

Subscribe:

Statistics

Subscribe to our newsletter