Radiological iodinated contrast-induced nephropathy

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Muñoz de Bustillo Llorente, E. de Miguel Balsa" "autores" => array:2 [ 0 => array:4 [ "nombre" => "E." "apellidos" => "Muñoz de Bustillo Llorente" "email" => array:1 [ 0 => "emunozd@senefro.org" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "E." 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A 60-year-old male patient with a history of tobacco use and arterial hypertension was admitted to an outpatient nephrology clinic presenting stage IIIA-A2 chronic kidney disease (CKD) (creatinine, 1.6mg/dL; estimated glomerular filtration rate [eGFR], 46.1mL/min/1.73m2 determined with the Chronic Kidney Disease Epidemiology Collaboration equation; microalbuminuria/creatinine ratio, 258mg/g). An ultrasound was requested, which incidentally detected a renal nodule requiring confirmation through computed axial tomography (CT) with iodinated contrast (IC). The radiology department asked whether a prophylactic regimen was needed before administering the IC.Case no. 2. A 77-year-old male patient with a history of stage IV-A3 CKD (creatinine, 3.4mg/dL; eGFR, 16.5mL/min/1.73m2; proteinuria, 0.7g/day) and arterial hypertension undergoing treatment with enalapril was admitted to the hospital due to heart failure but with a good response to diuretic treatment. The echocardiography detected severe mitral regurgitation and severe left ventricular dysfunction. The department of cardiology recommended cardiac catheterization to propose surgery. The department of nephrology was consulted given the risk of IC-induced renal toxicity.The clinical problemThe use of radiological techniques for diagnostic and therapeutic purposes is essential, and in many cases the administration of a contrast medium is required to improve its resolution. Since its introduction into clinical use in 1950, IC has been consolidated as the reference contrast medium for radiological examinations, and its consumption has progressively increased, especially since the introduction of CAT.<a class="elsevierStyleCrossRefs" href="#bib0330">1,2</a> Estimates from 2003 place the number of annual doses of IC worldwide at 80 million.<a class="elsevierStyleCrossRefs" href="#bib0330">1,2</a> Since the publishing of a case of anuria after administering IC in 1954,<a class="elsevierStyleCrossRef" href="#bib0340">3</a> there have been numerous references in the literature regarding acute renal failure (ARF) associated with this exposure, to the point where contrast-induced nephropathy (CIN) is considered the third leading cause of ARF in hospital settings, after renal perfusion reduction and the use of nephrotoxic drugs.<a class="elsevierStyleCrossRef" href="#bib0345">4</a> There is therefore widespread concern about the risks associated with administering IC to at-risk patients, which in practice leads to the avoidance of its use in clinical conditions that might need it, thereby limiting the diagnosis and/or appropriate treatment and determining the patient's therapeutic management. It has been reported that clinicians are less likely to prescribe IC for patients with some degree of renal failure, even for those patients with only slightly increased serum creatinine values.<a class="elsevierStyleCrossRef" href="#bib0350">5</a> However, there is considerable variability in the literature in terms of the incidence rate of CIN, ranging from 0.5% to 37%, depending on the criteria employed for defining the condition, the characteristics of the at-risk population and the type of radiological study conducted.<a class="elsevierStyleCrossRefs" href="#bib0355">6–12</a> In fact, publications in recent years have suggested that the actual impact of the problem could be significantly lower than previously estimated, at least with the current regimens for employing IC.<a class="elsevierStyleCrossRefs" href="#bib0350">5,13–22</a> A broad, recently published epidemiological study with a sample of 7,810,762 hospitalized patients in the United States during 2009, 5,922,537 of whom were analyzed, found no significant differences in the risk of presenting ARF between the group who were administered IC during their hospitalization and those who were not (5.5% vs. 5.6%, respectively).<a class="elsevierStyleCrossRef" href="#bib0440">23</a>DefinitionMost studies have defined CIN as an absolute increase in serum creatinine values ≥0.5mg/dL and/or a relative increase >25% of its baseline value that occurs 48–72h after administering IC.<a class="elsevierStyleCrossRef" href="#bib0445">24</a> However, the International Society of Nephrology (ISN) and recently the European Society of Urogenital Radiology (ESUR) have stated that there is no reason to use criteria other than those accepted for ARF of any other etiology. Thus, according to the Kidney Disease Improving Global Outcomes criteria, CIN is defined as an absolute increase of 0.3mg/dL in creatinine values and/or a >1.5-fold relative increase in baseline creatinine values that occurs 48–72h after exposure to IC.<a class="elsevierStyleCrossRefs" href="#bib0450">25,26</a> However, worsening renal function after IC administration is not always secondary to the administration of IC. Therefore, both the ESUR and the American College of Radiology prefer the term “post-contrast ARF” when there are other potentially pathogenic factors that can contribute to renal function impairment. The term CIN would be restricted to those cases that have a causal relationship between reduced glomerular filtration rate and IC exposure, which can only be demonstrated through studies that have a control group without exposure to the IC.<a class="elsevierStyleCrossRefs" href="#bib0450">25,27</a> Using this approach, many cases of renal function impairment are likely secondary to other concomitant factors in the patient and not directly related to the administration of IC.<a class="elsevierStyleCrossRefs" href="#bib0450">25,27</a> In fact, a study that compared fluctuations in serum creatinine levels during hospital admission in patients administered IC and in those not exposed to IC showed similar changes in renal function in the 2 groups.<a class="elsevierStyleCrossRef" href="#bib0465">28</a> The quality of the evidence is very low because there are no randomized studies, due to the nature of the problem, and there are very few studies that have included control groups without IC exposure. It is notable that most of these studies could not demonstrate a greater risk of nephropathy in the exposed patients<a class="elsevierStyleCrossRefs" href="#bib0350">5,16–21,29–33</a> or only observed it in patients at greater risk (such as those with eGFR <30mL/min/1.73m2)<a class="elsevierStyleCrossRef" href="#bib0495">34</a> or those in intensive care with an eGFR <45mL/min/1.73m2.<a class="elsevierStyleCrossRef" href="#bib0500">35</a>PathogenesisThere is abundant experimental evidence supporting the renal toxicity of IC, both in vitro and in vivo.<a class="elsevierStyleCrossRefs" href="#bib0505">36–40</a> Studies with animal models have shown direct toxicity on endothelial and renal tubular cells and damage secondary to the vasoconstriction mediated by the effects of IC on local vasoactive substances such as endothelin, nitric oxide and adenosine, which cause hypoperfusion, especially in the renal medulla.<a class="elsevierStyleCrossRefs" href="#bib0505">36,37,39,40</a> The hyperviscosity of IC has been shown to jeopardize renal hemodynamics, by reducing tubular flow and causing acute tubular damage.<a class="elsevierStyleCrossRef" href="#bib0515">38</a> It is interesting to note that most experimental models need to add some factor that predisposes to renal hypoxia so as to produce CIN, reproducing to a certain degree what is observed in the symptoms.<a class="elsevierStyleCrossRef" href="#bib0390">13</a>Clinical courseCIN typically progresses without oliguria,<a class="elsevierStyleCrossRef" href="#bib0530">41</a> and if oliguria does appear, it is usually transient and accompanied by a fractional excretion of sodium <1%, which suggests an associated prerenal component.<a class="elsevierStyleCrossRef" href="#bib0535">42</a> The sediment is anodyne and can occasionally show epithelial cylinders. Although de novo proteinuria by artifact was initially reported following the administration of ionic IC, this condition does not occur with nonionic IC, which is currently more often employed.<a class="elsevierStyleCrossRef" href="#bib0540">43</a> In most cases, peak serum creatinine values are reached between 48 and 72h after the administration of IC, after which there is a progressive recovery of renal function to baseline levels a week after the exposure.<a class="elsevierStyleCrossRefs" href="#bib0335">2,24,25</a> However, the progression is not always so favorable, especially for patients who have undergone cardiac catheterization.<a class="elsevierStyleCrossRefs" href="#bib0370">9,10,12</a> In a series of 3986 patients who underwent coronary angiography (12.1% of whom presented criteria of CIN), 18.6% had renal impairment 3 months after the procedure, with serum creatinine values at least 25% greater than baseline.<a class="elsevierStyleCrossRef" href="#bib0375">10</a> This result translated into a significant increase in cardiovascular events and mortality compared with those in whom the renal function remained stable, with a combined relative risk of 2.5 (1.5–4.2; p=.0001).<a class="elsevierStyleCrossRef" href="#bib0375">10</a> Some cases even required renal replacement therapy, as occurred in 0.3% of the 985,737 cardiac catheterizations (3005 cases) recorded by the US National Cardiovascular Data Registry Cath-PCI between 2009 and 2011.<a class="elsevierStyleCrossRef" href="#bib0385">12</a> These patients had a high rate of complications (myocardial infarction in 7.9% and hemorrhage in 15.8%) and high mortality (34.3%).<a class="elsevierStyleCrossRef" href="#bib0385">12</a>Differential diagnosisThe diagnosis of CIN requires ruling out other potential causes of ARF, the most important of which is atheroembolic disease, which should be ruled out in those cases in which the renal impairment occurs after an invasive procedure by an arterial pathway.<a class="elsevierStyleCrossRefs" href="#bib0445">24,44</a> A number of authors have considered that the excessive risk of CIN attributed to intra-arterial procedures is due in fact to cases of undiagnosed atheroembolism.<a class="elsevierStyleCrossRef" href="#bib0545">44</a> Although they do not occur in all cases, livedo reticularis, distal skin embolisms, hypocomplementemia and/or eosinophilia are sufficient for diagnosing this entity, which can be confirmed by visualizing the cholesterol emboli in the eye fundus or through skin biopsy.<a class="elsevierStyleCrossRef" href="#bib0545">44</a>Risk factorsProcedure-relatedIodinated contrast administration routeMost studies that have reported a high incidence of CIN refer to intra-arterial procedures in the context of cardiac catheterization.<a class="elsevierStyleCrossRefs" href="#bib0355">6,8–12,45</a> A series that included patients exposed to intravenous IC and patients who underwent cardiac catheterization observed CIN only in the latter patient group.<a class="elsevierStyleCrossRef" href="#bib0360">7</a> In fact, the latest publications that have specifically studied the risk of CIN associated with the administration of intravenous IC have not found significant differences compared with not administering IC.<a class="elsevierStyleCrossRefs" href="#bib0350">5,14–20,32</a> Using the statistical methodology of propensity analysis to reduce the typical biases of an observational study, McDonald et al. retrospectively analyzed 10,673 patients who underwent CT with intravenous IC during 2000–2010.<a class="elsevierStyleCrossRef" href="#bib0420">19</a> The patients were compared 1:1 with 10,673 patients who underwent CT without IC. The authors found no significant differences in the incidence of ARF (odds ratio [OR], 0.94; p=.38), emergency dialysis (OR, 0.96; p=.89) or mortality at 30 days (hazard ratio [HR], 0.97; p=.45). Using the same methodology, a series was recently published with 17,934 patients from a single emergency department over 5 years (2009–2014), 7201 of whom underwent contrast CT, 5499 underwent CT without contrast, and 5234 did not undergo a CT.<a class="elsevierStyleCrossRef" href="#bib0350">5</a> The series found no greater risk of ARF associated with IC exposure, even in the patients with serum creatinine levels >4mg/dL. This low risk has also been suggested by a recent meta-analysis of 28 observational studies with a total of 107,335 patients, which was unable to show a greater risk of CIN after performing CT with intravenous IC (OR, 0.96; 95% CI 0.85–1.08).<a class="elsevierStyleCrossRef" href="#bib0395">14</a> Therefore, the risk associated with the intra-arterial administration of IC appears greater than that of intravenously administered IC, at least in those cases in which the IC reached the renal arteries abruptly and relatively poorly diluted, i.e., when the injection occurred in the left heart, thoracic aorta or suprarenal abdominal and renal arteries (first-pass renal exposure).<a class="elsevierStyleCrossRef" href="#bib0555">46</a> These procedures also have a greater risk of renal atheroembolism.<a class="elsevierStyleCrossRefs" href="#bib0460">27,44</a>Iodinated contrast type and doseThe IC type also plays an important role in the development of CIN. IC can be ionic (with high or low osmolarity, such as diatrizoic and ioxaglic acid, respectively) and nonionic (with low osmolarity, such as iohexol, iobitridol, iomeprol, iopamidol, iopromide and ioversol, or iso-osmolar, such as iodixanol).<a class="elsevierStyleCrossRefs" href="#bib0335">2,47</a> When discussing low osmolarity, it is worth noting that these IC agents have much higher osmolality than that of plasma, approximately 520–695mOsm/kg H2O, and that the only truly iso-osmolar IC is iodixanol (290mOsm/kg H2O). However, iodixanol has higher viscosity than low-osmolar IC, which increases the possibility of adverse reactions.<a class="elsevierStyleCrossRef" href="#bib0560">47</a> A greater risk of CIN associated with high-osmolar IC seems apparent, and these IC agents have therefore fallen into disuse.<a class="elsevierStyleCrossRef" href="#bib0565">48</a> Although initial studies reported a lower risk of CIN associated with the use of iso-osmolar IC such as iodixanol,<a class="elsevierStyleCrossRef" href="#bib0380">11</a> 2 subsequent meta-analyses have suggested that this advantage is observed exclusively when compared with iohexol but not against other low-osmolar IC agents.<a class="elsevierStyleCrossRefs" href="#bib0570">49,50</a> Regardless of the IC type, the dose is fundamental to the pathogenesis,<a class="elsevierStyleCrossRefs" href="#bib0355">6,9,10,24</a> such that the incidence of CIN can double when the dose exceeds 300mL in a single procedure.<a class="elsevierStyleCrossRef" href="#bib0370">9</a> A significant reduction in the risk of kidney injury has also been shown with the use of techniques that minimize the administration of IC.<a class="elsevierStyleCrossRef" href="#bib0580">51</a>Patient-relatedRenal functionPrevious renal failure has classically been considered the main predisposing factor for developing CIN according to numerous observational studies, with a risk that progressively increases as the eGFR decreases.<a class="elsevierStyleCrossRefs" href="#bib0330">1,6,10,12,24,26</a> However, this association appears less clear when studies are performed with propensity analysis. A series employed this methodology to compare 8826 patients who underwent intravenous IC with 8826 who underwent the study without IC and found only a significantly greater risk of CIN in those with eGFR <30mL/min/1.73m2.<a class="elsevierStyleCrossRef" href="#bib0495">34</a> A series of 12,508 patients that matched patients according to their eGFR observed no greater risk in those who had been administered IC than in those who were not administered IC, even in the patient group with eGFR <30mL/min/1.73m2.<a class="elsevierStyleCrossRef" href="#bib0415">18</a> Therefore, neither the American College of Radiology nor the Royal Australian and New Zealand College of Radiologists consider that there is currently definitive evidence that renal failure constitutes an independent factor for developing CIN, at least when the eGFR is >30mL/min/1.73m2.<a class="elsevierStyleCrossRefs" href="#bib0460">27,52</a>Other factorsThe other clinical conditions that have been associated with a greater risk of CIN are diabetes mellitus,<a class="elsevierStyleCrossRefs" href="#bib0355">6,10,12,24,26</a> advanced age,<a class="elsevierStyleCrossRefs" href="#bib0375">10,12,24,26</a> left ventricular dysfunction,<a class="elsevierStyleCrossRefs" href="#bib0355">6,10,12,24,26,45</a> anemia<a class="elsevierStyleCrossRefs" href="#bib0375">10,24,26</a> and in general any condition that can result in a greater risk of developing prerenal renal failure (e.g., dehydration, arterial hypotension, sepsis, hepatic cirrhosis).<a class="elsevierStyleCrossRefs" href="#bib0445">24,26</a> In contrast to the above, monoclonal gammopathies do not appear to be associated with a greater risk of CIN.<a class="elsevierStyleCrossRef" href="#bib0590">53</a>Concomitant medicationThe role played by drugs in the pathogenesis of CIN deserves special mention, given that this is a modifiable factor. The use of any nephrotoxic drug (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>) should be avoided, although there is no conclusive evidence that this type of drug should be withdrawn prior to IC administration.<a class="elsevierStyleCrossRef" href="#bib0555">46</a> The potential deleterious effect of renin-angiotensin-aldosterone system (RAAS) blockers is controversial. Employing a propensity analysis, a retrospective analysis compared 1322 patients who underwent cardiac catheterization and undergoing treatment with this drug against a control group without treatment.<a class="elsevierStyleCrossRef" href="#bib0595">54</a> The analysis observed a higher incidence of CIN in the group treated with the RAAS blocker (11.4% vs. 6.3%; p<.001).<a class="elsevierStyleCrossRef" href="#bib0595">54</a> However, a randomized prospective study with 208 patients with serum creatinine levels >1.7mg/dL, 108 of whom had the drug withdrawn before performing cardiac catheterization, could not demonstrate a significant reduction in the risk of CIN (10.9% vs. 18.4%; HR, 0.59; p=.16).<a class="elsevierStyleCrossRef" href="#bib0600">55</a> Although a number of authors have recommended withdrawing angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers prior to cardiac catheterization in patients with CKD,<a class="elsevierStyleCrossRef" href="#bib0605">56</a> the ESUR guidelines do not consider this withdrawal necessary.<a class="elsevierStyleCrossRef" href="#bib0555">46</a> Lastly, the classic recommendation of discontinuing metformin before administering IC is not because metformin increases its toxicity but because of the risk that worsening renal function after exposure to IC can result in poisoning by metformin, as well as secondary lactic acidosis.<a class="elsevierStyleCrossRef" href="#bib0460">27</a><elsevierMultimedia ident="tbl0005"></elsevierMultimedia>PreventionLimiting exposureObviously, the best prevention for CIN is to avoid administering IC when not essential, choosing other diagnostic techniques that do not require IC or postponing the procedure until the patient's clinical and renal situation are more favorable.<a class="elsevierStyleCrossRef" href="#bib0460">27</a> If IC administration is essential, the amount of IC should be minimized, maintaining a total dose <4mL/kg (or adjusted to renal function with the following formula: total volume/eGFR <3.4), and not re-administering within a short period.<a class="elsevierStyleCrossRef" href="#bib0610">57</a>Fluid therapyHydration with 0.9% isotonic saline solution before and after the radiological procedure is the main prophylaxis for CIN for patients considered at high risk<a class="elsevierStyleCrossRefs" href="#bib0350">5,7,26,27,46,52,57–59</a> (class I recommendation, level of evidence A for the European Society of Cardiology [ESC] guidelines<a class="elsevierStyleCrossRef" href="#bib0610">57</a> and B for the ESUR guidelines<a class="elsevierStyleCrossRef" href="#bib0555">46</a>). However, a recent, randomized, prospective controlled study was conducted with 660 patients with stage III CKD who underwent IC, 328 of whom were treated with prophylaxis based on hydration with 0.9% saline solution, and 332 were not treated with prophylaxis. The study observed no differences in terms of developing CIN (2.6% vs. 2.7%; p=.471) but did observe an increase in cost and complications due to the development of heart failure in 13 of the 328 patients who underwent volume expansion (compared with none in the no prophylaxis arm; p=.0001).<a class="elsevierStyleCrossRef" href="#bib0625">60</a> This study therefore raises uncertainty as to the relevance of hydration, at least in those patients with eGFR >30mL/min/1.73m2.There has been discussion in recent years regarding the potential advantages of administering a bicarbonate solution over 0.9% saline solution for preventing CIN. The recently published study PRESERVE attempted to clarify both this aspect and the potential role of acetylcysteine in preventing CIN.<a class="elsevierStyleCrossRef" href="#bib0630">61</a> PRESERVE was the largest prospective, randomized study to date, with 5177 patients with eGFRs of 15–59.9mL/min/1.73m2, and was unable to demonstrate significant differences between the 2 solutions (0.9% saline solution vs. 1.26% bicarbonate).<a class="elsevierStyleCrossRef" href="#bib0630">61</a> The main guidelines still consider isotonic saline solution as the reference fluid therapy for preventing CIN,<a class="elsevierStyleCrossRefs" href="#bib0460">27,52,57</a> although the latest revision of the ESUR guidelines still recommend both solutions interchangeably.<a class="elsevierStyleCrossRef" href="#bib0555">46</a> The proposed hydration protocols include the infusion of 1–3mL/kg/h from 1 to 12h before the procedure to 2–12h afterwards, depending on the patient's clinical situation and risk of developing heart failure.<a class="elsevierStyleCrossRefs" href="#bib0460">27,46,61</a> There are more complex protocols aimed at patients who will undergo cardiac catheterization that include administering saline solution at a faster rate (250mL/h) along with a bolus of furosemide<a class="elsevierStyleCrossRef" href="#bib0610">57</a> or adjusting the fluid infusion according to hemodynamic parameters.<a class="elsevierStyleCrossRef" href="#bib0615">58</a>DrugsAcetylcysteine has been regularly included in the prophylaxis protocols for CIN in recent years, although its usefulness has been highly controversial.<a class="elsevierStyleCrossRefs" href="#bib0635">62,63</a> The definitive evidence appears to have arrived with the previously mentioned PRESERVE study, which was unable to demonstrate any protective effect of the antioxidant drug in this context.<a class="elsevierStyleCrossRef" href="#bib0630">61</a> The most recent guidelines no longer recommend the use of acetylcysteine.<a class="elsevierStyleCrossRefs" href="#bib0460">27,46,52,57</a>The use of high-dose statins in a single administration within 24h prior to cardiac catheterization (40–80mg of atorvastatin or 20–40mg of rosuvastatin) has recently been related to a lower incidence of CIN.<a class="elsevierStyleCrossRefs" href="#bib0365">8,64,65</a> High-dose statins have therefore been included in the ESC guidelines (class IIa recommendation and level of evidence A), although the recent ESUR guidelines consider the evidence still insufficient to recommend high-dose statins.<a class="elsevierStyleCrossRefs" href="#bib0555">46,57</a> The nephroprotective mechanism of action is related to its pleiotropic effects through a reduced cell apoptosis and reduced IC-induced oxidative stress.<a class="elsevierStyleCrossRef" href="#bib0365">8</a>Other tested drugs such as ascorbic acid, theophylline, alprostadil, iloprost and fenoldopam have not provided solid evidence of a beneficial effect and are therefore not recommended.<a class="elsevierStyleCrossRefs" href="#bib0460">27,46</a>Renal replacement therapyThe relatively low molecular weight of current IC agents, their low osmolarity and no protein binding enable excellent elimination through hemodialysis and hemofiltration, although the use of these techniques is not recommended for preventing CIN.<a class="elsevierStyleCrossRefs" href="#bib0455">26,27,46,57,59</a> Hemodialysis may be considered only for those patients with stage V CKD who have still not started replacement therapy but who already have a vascular access and for whom rapid IC elimination following the procedure could potentially reduce its renal toxicity. In terms of hemofiltration, only the ESC guidelines mention its use before and after cardiac catheterization in complex cases with a high risk of CIN due to advanced CKD (class IIb recommendation with a level of evidence B).<a class="elsevierStyleCrossRef" href="#bib0610">57</a> Given that IC does not present toxicity other than renal, its administration does not suppose a risk for patients with enuresis undergoing dialysis.<a class="elsevierStyleCrossRefs" href="#bib0460">27,46</a> Regardless, if there is no emergency, the standard practice is to schedule the radiological procedures with IC before a hemodialysis session with these patients.Conclusions<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005">1The use of the term CIN should be restricted to those cases in which a causal relationship can be demonstrated between the administration of IC and renal impairment. For all others (i.e., the majority), the term postcontrast ARF is recommended.</li><li class="elsevierStyleListItem" id="lsti0010">2The actual impact of CIN appears lower than previously believed, especially in those cases in which IC administration is performed intravenously and with current usage regimens.</li><li class="elsevierStyleListItem" id="lsti0015">3Administering IC to patients with renal failure should be avoided if not essential.</li><li class="elsevierStyleListItem" id="lsti0020">4The latest guidelines suggest that administering IC to patients with an eGFR >45mL/min/1.73m2 can be considered safe. Below this threshold, the risk of renal toxicity cannot be ruled out, especially in intra-arterial procedures with first-pass renal exposure and in those patients with stage IV-V CKD (eGFR <30mL/min/1.73m2).</li><li class="elsevierStyleListItem" id="lsti0025">5The risk of renal toxicity should not be the reason for not administering IC if essential at that moment for the patient's correct diagnosis and treatment.</li><li class="elsevierStyleListItem" id="lsti0030">6To minimize the incidence of CIN, the recommendation is to use the least amount of iso-osmolar or low-osmolar IC possible (any, with the possible exception of iohexol) and ensure the patient's adequate hydration with isotonic saline solution if there is no risk of heart failure.</li></ul>Case resolutionCaso no. 1 Faced with a low risk of CIN due to the patient's baseline renal function and an absence of concomitant prerenal factors, CT was performed without prophylactic measures with 100mL of iodixanol; renal function remained stable during the follow-up.Caso no. 2 The patient was considered at risk for developing CIN. Therefore, once the patient's heart failure was compensated, an infusion of 1.5mL/k/h of 0.9% isotonic saline solution was administered from 6h before the catheterization to 6h after the procedure, and an 80-mg dose of atorvastatin was administered 12h before the procedure. The procedure was performed while minimizing the IC dose (60mL of iodixanol). A laboratory check 72h later confirmed the stability of the creatinine values.Conflicts of interestThe authors declare that they have no conflicts of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:16 [ 0 => array:3 [ "identificador" => "xres1276559" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1180660" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1276560" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1180661" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Cases studies" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "The clinical problem" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Definition" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Pathogenesis" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Clinical course" ] 9 => array:2 [ "identificador" => "sec0030" "titulo" => "Differential diagnosis" ] 10 => array:3 [ "identificador" => "sec0035" "titulo" => "Risk factors" "secciones" => array:3 [ 0 => array:3 [ "identificador" => "sec0040" "titulo" => "Procedure-related" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0045" "titulo" => "Iodinated contrast administration route" ] 1 => array:2 [ "identificador" => "sec0050" "titulo" => "Iodinated contrast type and dose" ] ] ] 1 => array:3 [ "identificador" => "sec0055" "titulo" => "Patient-related" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0060" "titulo" => "Renal function" ] 1 => array:2 [ "identificador" => "sec0065" "titulo" => "Other factors" ] ] ] 2 => array:2 [ "identificador" => "sec0070" "titulo" => "Concomitant medication" ] ] ] 11 => array:3 [ "identificador" => "sec0075" "titulo" => "Prevention" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0080" "titulo" => "Limiting exposure" ] 1 => array:2 [ "identificador" => "sec0085" "titulo" => "Fluid therapy" ] 2 => array:2 [ "identificador" => "sec0090" "titulo" => "Drugs" ] 3 => array:2 [ "identificador" => "sec0095" "titulo" => "Renal replacement therapy" ] ] ] 12 => array:2 [ "identificador" => "sec0100" "titulo" => "Conclusions" ] 13 => array:2 [ "identificador" => "sec0105" "titulo" => "Case resolution" ] 14 => array:2 [ "identificador" => "sec0110" "titulo" => "Conflicts of interest" ] 15 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2018-09-03" "fechaAceptado" => "2018-09-04" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1180660" "palabras" => array:4 [ 0 => "Contrast-induced nephropathy" 1 => "Post-contrast acute renal failure" 2 => "Chronic kidney disease" 3 => "Iodinated contrast" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1180661" "palabras" => array:4 [ 0 => "Nefropatía inducida por contraste" 1 => "Fracaso renal agudo poscontraste" 2 => "Enfermedad renal crónica" 3 => "Contraste iodado" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "The use of iodinated contrast media can cause renal toxicity. Whether contrast media are exclusively responsible for kidney damage is currently the subject of debate, given that in most cases, other potential causes of the renal failure are present. With current low-osmolar and iso-osmolar contrast media, the incidence rate of contrast-induced nephropathy is estimated to be <1% in the low-risk population but can increase to 37% in patients who are administered contrast by an intra-arterial administration and/or who have renal failure with an estimated glomerular filtration rate (eGFR) <30mL/min/1.73m2. To minimize the risk of renal toxicity, the recommendation is to administer the least amount of contrast possible and ensure appropriate volume expansion by infusing 0.9% saline solution." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "El uso de contrastes iodados puede causar nefrotoxicidad. Actualmente se cuestiona que los contrastes sean los responsables exclusivos del daño renal, ya que en la mayoría de los casos coexisten otras causas potenciales de fracaso renal. Con los contrastes actuales de baja osmolaridad e isoosmolares, la incidencia de nefropatía por contraste se estima que es inferior al 1% en la población de bajo riesgo; pero puede incrementarse hasta el 37% en pacientes que reciben contraste por vía intraarterial y/o que presentan insuficiencia renal con filtrado glomerular estimado inferior a 30ml/min/1.73m2. Para minimizar el riesgo de nefrotoxicidad se recomienda administrar la menor cantidad posible de contraste y asegurar una adecuada expansión de volumen mediante la infusión de solución salina 0,9%." ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Muñoz de Bustillo Llorente E, de Miguel Balsa E. Nefropatía inducida por contrastes iodados radiológicos. Rev Clín Esp. 2018. https://doi.org/10.1016/j.rce.2018.09.004" ] ] "multimedia" => array:1 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "Abbreviations: NSAIDs, anti-inflammatory nonsteroidal drugs; CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration; eGFR, estimated glomerular filtration rate; RAAS, renin-angiotensin-aldosterone system." "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"><th 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" scope="col" style="border-bottom: 2px solid black">Risk factors \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">Prevention \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">Monitoring \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Procedure-related \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 " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Use iso-osmolar or low-osmolar contrast (except iohexol)</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Determine baseline renal function (eGFR CKD-EPI)</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Greater risk by intra-arterial pathway than by intravenous \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Contrast 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">Administer minimum effective doses of contrast (<4mL/kg or volume/eGFR <3.4) \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">If baseline eGFR is <45mL/min/1.73m2, perform a check at 72h \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 " colspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Patient-related \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 " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Administer intravenous hydration with 1–3mL/kg/h of 0.9% saline serum from 1 to 12h before the procedure to 2–12h after the procedure.</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">If the eGFR drops at 72h, repeat the measurement at 14 days</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Renal failure (eGFR <45mL/min/1.73m2) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Diabetes mellitus \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">Administer 40–80mg of atorvastatin or 20–40mg of rosuvastatin in a single dose 12h before a cardiac catheterization? \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></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Left ventricle dysfunction \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="" 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-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Anemia \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="" 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-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Advanced age \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="" 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-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Prerenal factors: sepsis, hypotension, dehydration, hepatic cirrhosis \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="" 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 " colspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Drugs \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="" 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-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NSAIDs, aminoglycosides, amphotericin B, acyclovir, foscarnet, anticalcineurin agents, cis-platinum. \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="" 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-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">RAAS blockers? \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="" 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-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">High-dose diuretics? \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="" 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></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2183521.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Predisposing factors for developing iodinated contrast-induced nephropathy and prevention and monitoring measures for patients at risk." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:65 [ 0 => array:3 [ "identificador" => "bib0330" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Contrast-induced nephrotoxicity: clinical landscape" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "R.W. 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Radiological iodinated contrast-induced nephropathy

Nefropatía inducida por contrastes iodados radiológicos

E. Muñoz de Bustillo Llorentea,

Corresponding author

emunozd@senefro.org

Corresponding author.

, E. de Miguel Balsab

a Sección de Nefrología, Hospital Marina Baixa, Villajoyosa, Alicante, Spain

b Servicio de Medicina Intensiva, Hospital General Universitario de Elche, Elche, Alicante, Spain

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Cases studies</span><p id="par0005" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Case no&#46; 1</span>&#46; A 60-year-old male patient with a history of tobacco use and arterial hypertension was admitted to an outpatient nephrology clinic presenting stage IIIA-A2 chronic kidney disease &#40;CKD&#41; &#40;creatinine&#44; 1&#46;6<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#59; estimated glomerular filtration rate &#91;eGFR&#93;&#44; 46&#46;1<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#47;1&#46;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span> determined with the Chronic Kidney Disease Epidemiology Collaboration equation&#59; microalbuminuria&#47;creatinine ratio&#44; 258<span class="elsevierStyleHsp" style=""></span>mg&#47;g&#41;&#46; An ultrasound was requested&#44; which incidentally detected a renal nodule requiring confirmation through computed axial tomography &#40;CT&#41; with iodinated contrast &#40;IC&#41;&#46; The radiology department asked whether a prophylactic regimen was needed before administering the IC&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Case no&#46; 2</span>&#46; A 77-year-old male patient with a history of stage IV-A3 CKD &#40;creatinine&#44; 3&#46;4<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#59; eGFR&#44; 16&#46;5<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#47;1&#46;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>&#59; proteinuria&#44; 0&#46;7<span class="elsevierStyleHsp" style=""></span>g&#47;day&#41; and arterial hypertension undergoing treatment with enalapril was admitted to the hospital due to heart failure but with a good response to diuretic treatment&#46; The echocardiography detected severe mitral regurgitation and severe left ventricular dysfunction&#46; The department of cardiology recommended cardiac catheterization to propose surgery&#46; The department of nephrology was consulted given the risk of IC-induced renal toxicity&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">The clinical problem</span><p id="par0015" class="elsevierStylePara elsevierViewall">The use of radiological techniques for diagnostic and therapeutic purposes is essential&#44; and in many cases the administration of a contrast medium is required to improve its resolution&#46; Since its introduction into clinical use in 1950&#44; IC has been consolidated as the reference contrast medium for radiological examinations&#44; and its consumption has progressively increased&#44; especially since the introduction of CAT&#46;<a class="elsevierStyleCrossRefs" href="#bib0330"><span class="elsevierStyleSup">1&#44;2</span></a> Estimates from 2003 place the number of annual doses of IC worldwide at 80 million&#46;<a class="elsevierStyleCrossRefs" href="#bib0330"><span class="elsevierStyleSup">1&#44;2</span></a> Since the publishing of a case of anuria after administering IC in 1954&#44;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">3</span></a> there have been numerous references in the literature regarding acute renal failure &#40;ARF&#41; associated with this exposure&#44; to the point where contrast-induced nephropathy &#40;CIN&#41; is considered the third leading cause of ARF in hospital settings&#44; after renal perfusion reduction and the use of nephrotoxic drugs&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">4</span></a> There is therefore widespread concern about the risks associated with administering IC to at-risk patients&#44; which in practice leads to the avoidance of its use in clinical conditions that might need it&#44; thereby limiting the diagnosis and&#47;or appropriate treatment and determining the patient&#39;s therapeutic management&#46; It has been reported that clinicians are less likely to prescribe IC for patients with some degree of renal failure&#44; even for those patients with only slightly increased serum creatinine values&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">5</span></a> However&#44; there is considerable variability in the literature in terms of the incidence rate of CIN&#44; ranging from 0&#46;5&#37; to 37&#37;&#44; depending on the criteria employed for defining the condition&#44; the characteristics of the at-risk population and the type of radiological study conducted&#46;<a class="elsevierStyleCrossRefs" href="#bib0355"><span class="elsevierStyleSup">6&#8211;12</span></a> In fact&#44; publications in recent years have suggested that the actual impact of the problem could be significantly lower than previously estimated&#44; at least with the current regimens for employing IC&#46;<a class="elsevierStyleCrossRefs" href="#bib0350"><span class="elsevierStyleSup">5&#44;13&#8211;22</span></a> A broad&#44; recently published epidemiological study with a sample of 7&#44;810&#44;762 hospitalized patients in the United States during 2009&#44; 5&#44;922&#44;537 of whom were analyzed&#44; found no significant differences in the risk of presenting ARF between the group who were administered IC during their hospitalization and those who were not &#40;5&#46;5&#37; vs&#46; 5&#46;6&#37;&#44; respectively&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">23</span></a></p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Definition</span><p id="par0020" class="elsevierStylePara elsevierViewall">Most studies have defined CIN as an absolute increase in serum creatinine values &#8805;0&#46;5<span class="elsevierStyleHsp" style=""></span>mg&#47;dL and&#47;or a relative increase &#62;25&#37; of its baseline value that occurs 48&#8211;72<span class="elsevierStyleHsp" style=""></span>h after administering IC&#46;<a class="elsevierStyleCrossRef" href="#bib0445"><span class="elsevierStyleSup">24</span></a> However&#44; the International Society of Nephrology &#40;ISN&#41; and recently the European Society of Urogenital Radiology &#40;ESUR&#41; have stated that there is no reason to use criteria other than those accepted for ARF of any other etiology&#46; Thus&#44; according to the Kidney Disease Improving Global Outcomes criteria&#44; CIN is defined as an absolute increase of 0&#46;3<span class="elsevierStyleHsp" style=""></span>mg&#47;dL in creatinine values and&#47;or a &#62;1&#46;5-fold relative increase in baseline creatinine values that occurs 48&#8211;72<span class="elsevierStyleHsp" style=""></span>h after exposure to IC&#46;<a class="elsevierStyleCrossRefs" href="#bib0450"><span class="elsevierStyleSup">25&#44;26</span></a> However&#44; worsening renal function after IC administration is not always secondary to the administration of IC&#46; Therefore&#44; both the ESUR and the American College of Radiology prefer the term &#8220;post-contrast ARF&#8221; when there are other potentially pathogenic factors that can contribute to renal function impairment&#46; The term CIN would be restricted to those cases that have a causal relationship between reduced glomerular filtration rate and IC exposure&#44; which can only be demonstrated through studies that have a control group without exposure to the IC&#46;<a class="elsevierStyleCrossRefs" href="#bib0450"><span class="elsevierStyleSup">25&#44;27</span></a> Using this approach&#44; many cases of renal function impairment are likely secondary to other concomitant factors in the patient and not directly related to the administration of IC&#46;<a class="elsevierStyleCrossRefs" href="#bib0450"><span class="elsevierStyleSup">25&#44;27</span></a> In fact&#44; a study that compared fluctuations in serum creatinine levels during hospital admission in patients administered IC and in those not exposed to IC showed similar changes in renal function in the 2 groups&#46;<a class="elsevierStyleCrossRef" href="#bib0465"><span class="elsevierStyleSup">28</span></a> The quality of the evidence is very low because there are no randomized studies&#44; due to the nature of the problem&#44; and there are very few studies that have included control groups without IC exposure&#46; It is notable that most of these studies could not demonstrate a greater risk of nephropathy in the exposed patients<a class="elsevierStyleCrossRefs" href="#bib0350"><span class="elsevierStyleSup">5&#44;16&#8211;21&#44;29&#8211;33</span></a> or only observed it in patients at greater risk &#40;such as those with eGFR &#60;30<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#47;1&#46;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>&#41;<a class="elsevierStyleCrossRef" href="#bib0495"><span class="elsevierStyleSup">34</span></a> or those in intensive care with an eGFR &#60;45<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#47;1&#46;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0500"><span class="elsevierStyleSup">35</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Pathogenesis</span><p id="par0025" class="elsevierStylePara elsevierViewall">There is abundant experimental evidence supporting the renal toxicity of IC&#44; both in vitro and in vivo&#46;<a class="elsevierStyleCrossRefs" href="#bib0505"><span class="elsevierStyleSup">36&#8211;40</span></a> Studies with animal models have shown direct toxicity on endothelial and renal tubular cells and damage secondary to the vasoconstriction mediated by the effects of IC on local vasoactive substances such as endothelin&#44; nitric oxide and adenosine&#44; which cause hypoperfusion&#44; especially in the renal medulla&#46;<a class="elsevierStyleCrossRefs" href="#bib0505"><span class="elsevierStyleSup">36&#44;37&#44;39&#44;40</span></a> The hyperviscosity of IC has been shown to jeopardize renal hemodynamics&#44; by reducing tubular flow and causing acute tubular damage&#46;<a class="elsevierStyleCrossRef" href="#bib0515"><span class="elsevierStyleSup">38</span></a> It is interesting to note that most experimental models need to add some factor that predisposes to renal hypoxia so as to produce CIN&#44; reproducing to a certain degree what is observed in the symptoms&#46;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">13</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Clinical course</span><p id="par0030" class="elsevierStylePara elsevierViewall">CIN typically progresses without oliguria&#44;<a class="elsevierStyleCrossRef" href="#bib0530"><span class="elsevierStyleSup">41</span></a> and if oliguria does appear&#44; it is usually transient and accompanied by a fractional excretion of sodium &#60;1&#37;&#44; which suggests an associated prerenal component&#46;<a class="elsevierStyleCrossRef" href="#bib0535"><span class="elsevierStyleSup">42</span></a> The sediment is anodyne and can occasionally show epithelial cylinders&#46; Although de novo proteinuria by artifact was initially reported following the administration of ionic IC&#44; this condition does not occur with nonionic IC&#44; which is currently more often employed&#46;<a class="elsevierStyleCrossRef" href="#bib0540"><span class="elsevierStyleSup">43</span></a> In most cases&#44; peak serum creatinine values are reached between 48 and 72<span class="elsevierStyleHsp" style=""></span>h after the administration of IC&#44; after which there is a progressive recovery of renal function to baseline levels a week after the exposure&#46;<a class="elsevierStyleCrossRefs" href="#bib0335"><span class="elsevierStyleSup">2&#44;24&#44;25</span></a> However&#44; the progression is not always so favorable&#44; especially for patients who have undergone cardiac catheterization&#46;<a class="elsevierStyleCrossRefs" href="#bib0370"><span class="elsevierStyleSup">9&#44;10&#44;12</span></a> In a series of 3986 patients who underwent coronary angiography &#40;12&#46;1&#37; of whom presented criteria of CIN&#41;&#44; 18&#46;6&#37; had renal impairment 3 months after the procedure&#44; with serum creatinine values at least 25&#37; greater than baseline&#46;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">10</span></a> This result translated into a significant increase in cardiovascular events and mortality compared with those in whom the renal function remained stable&#44; with a combined relative risk of 2&#46;5 &#40;1&#46;5&#8211;4&#46;2&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;0001&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">10</span></a> Some cases even required renal replacement therapy&#44; as occurred in 0&#46;3&#37; of the 985&#44;737 cardiac catheterizations &#40;3005 cases&#41; recorded by the US National Cardiovascular Data Registry Cath-PCI between 2009 and 2011&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">12</span></a> These patients had a high rate of complications &#40;myocardial infarction in 7&#46;9&#37; and hemorrhage in 15&#46;8&#37;&#41; and high mortality &#40;34&#46;3&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">12</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Differential diagnosis</span><p id="par0035" class="elsevierStylePara elsevierViewall">The diagnosis of CIN requires ruling out other potential causes of ARF&#44; the most important of which is atheroembolic disease&#44; which should be ruled out in those cases in which the renal impairment occurs after an invasive procedure by an arterial pathway&#46;<a class="elsevierStyleCrossRefs" href="#bib0445"><span class="elsevierStyleSup">24&#44;44</span></a> A number of authors have considered that the excessive risk of CIN attributed to intra-arterial procedures is due in fact to cases of undiagnosed atheroembolism&#46;<a class="elsevierStyleCrossRef" href="#bib0545"><span class="elsevierStyleSup">44</span></a> Although they do not occur in all cases&#44; livedo reticularis&#44; distal skin embolisms&#44; hypocomplementemia and&#47;or eosinophilia are sufficient for diagnosing this entity&#44; which can be confirmed by visualizing the cholesterol emboli in the eye fundus or through skin biopsy&#46;<a class="elsevierStyleCrossRef" href="#bib0545"><span class="elsevierStyleSup">44</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Risk factors</span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Procedure-related</span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Iodinated contrast administration route</span><p id="par0040" class="elsevierStylePara elsevierViewall">Most studies that have reported a high incidence of CIN refer to intra-arterial procedures in the context of cardiac catheterization&#46;<a class="elsevierStyleCrossRefs" href="#bib0355"><span class="elsevierStyleSup">6&#44;8&#8211;12&#44;45</span></a> A series that included patients exposed to intravenous IC and patients who underwent cardiac catheterization observed CIN only in the latter patient group&#46;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">7</span></a> In fact&#44; the latest publications that have specifically studied the risk of CIN associated with the administration of intravenous IC have not found significant differences compared with not administering IC&#46;<a class="elsevierStyleCrossRefs" href="#bib0350"><span class="elsevierStyleSup">5&#44;14&#8211;20&#44;32</span></a> Using the statistical methodology of propensity analysis to reduce the typical biases of an observational study&#44; McDonald et al&#46; retrospectively analyzed 10&#44;673 patients who underwent CT with intravenous IC during 2000&#8211;2010&#46;<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">19</span></a> The patients were compared 1&#58;1 with 10&#44;673 patients who underwent CT without IC&#46; The authors found no significant differences in the incidence of ARF &#40;odds ratio &#91;OR&#93;&#44; 0&#46;94&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;38&#41;&#44; emergency dialysis &#40;OR&#44; 0&#46;96&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;89&#41; or mortality at 30 days &#40;hazard ratio &#91;HR&#93;&#44; 0&#46;97&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;45&#41;&#46; Using the same methodology&#44; a series was recently published with 17&#44;934 patients from a single emergency department over 5 years &#40;2009&#8211;2014&#41;&#44; 7201 of whom underwent contrast CT&#44; 5499 underwent CT without contrast&#44; and 5234 did not undergo a CT&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">5</span></a> The series found no greater risk of ARF associated with IC exposure&#44; even in the patients with serum creatinine levels &#62;4<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#46; This low risk has also been suggested by a recent meta-analysis of 28 observational studies with a total of 107&#44;335 patients&#44; which was unable to show a greater risk of CIN after performing CT with intravenous IC &#40;OR&#44; 0&#46;96&#59; 95&#37; CI 0&#46;85&#8211;1&#46;08&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">14</span></a> Therefore&#44; the risk associated with the intra-arterial administration of IC appears greater than that of intravenously administered IC&#44; at least in those cases in which the IC reached the renal arteries abruptly and relatively poorly diluted&#44; i&#46;e&#46;&#44; when the injection occurred in the left heart&#44; thoracic aorta or suprarenal abdominal and renal arteries &#40;first-pass renal exposure&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">46</span></a> These procedures also have a greater risk of renal atheroembolism&#46;<a class="elsevierStyleCrossRefs" href="#bib0460"><span class="elsevierStyleSup">27&#44;44</span></a></p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Iodinated contrast type and dose</span><p id="par0045" class="elsevierStylePara elsevierViewall">The IC type also plays an important role in the development of CIN&#46; IC can be ionic &#40;with high or low osmolarity&#44; such as diatrizoic and ioxaglic acid&#44; respectively&#41; and nonionic &#40;with low osmolarity&#44; such as iohexol&#44; iobitridol&#44; iomeprol&#44; iopamidol&#44; iopromide and ioversol&#44; or iso-osmolar&#44; such as iodixanol&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0335"><span class="elsevierStyleSup">2&#44;47</span></a> When discussing low osmolarity&#44; it is worth noting that these IC agents have much higher osmolality than that of plasma&#44; approximately 520&#8211;695<span class="elsevierStyleHsp" style=""></span>mOsm&#47;kg H<span class="elsevierStyleInf">2</span>O&#44; and that the only truly iso-osmolar IC is iodixanol &#40;290<span class="elsevierStyleHsp" style=""></span>mOsm&#47;kg H<span class="elsevierStyleInf">2</span>O&#41;&#46; However&#44; iodixanol has higher viscosity than low-osmolar IC&#44; which increases the possibility of adverse reactions&#46;<a class="elsevierStyleCrossRef" href="#bib0560"><span class="elsevierStyleSup">47</span></a> A greater risk of CIN associated with high-osmolar IC seems apparent&#44; and these IC agents have therefore fallen into disuse&#46;<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">48</span></a> Although initial studies reported a lower risk of CIN associated with the use of iso-osmolar IC such as iodixanol&#44;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">11</span></a> 2 subsequent meta-analyses have suggested that this advantage is observed exclusively when compared with iohexol but not against other low-osmolar IC agents&#46;<a class="elsevierStyleCrossRefs" href="#bib0570"><span class="elsevierStyleSup">49&#44;50</span></a> Regardless of the IC type&#44; the dose is fundamental to the pathogenesis&#44;<a class="elsevierStyleCrossRefs" href="#bib0355"><span class="elsevierStyleSup">6&#44;9&#44;10&#44;24</span></a> such that the incidence of CIN can double when the dose exceeds 300<span class="elsevierStyleHsp" style=""></span>mL in a single procedure&#46;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">9</span></a> A significant reduction in the risk of kidney injury has also been shown with the use of techniques that minimize the administration of IC&#46;<a class="elsevierStyleCrossRef" href="#bib0580"><span class="elsevierStyleSup">51</span></a></p></span></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Patient-related</span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Renal function</span><p id="par0050" class="elsevierStylePara elsevierViewall">Previous renal failure has classically been considered the main predisposing factor for developing CIN according to numerous observational studies&#44; with a risk that progressively increases as the eGFR decreases&#46;<a class="elsevierStyleCrossRefs" href="#bib0330"><span class="elsevierStyleSup">1&#44;6&#44;10&#44;12&#44;24&#44;26</span></a> However&#44; this association appears less clear when studies are performed with propensity analysis&#46; A series employed this methodology to compare 8826 patients who underwent intravenous IC with 8826 who underwent the study without IC and found only a significantly greater risk of CIN in those with eGFR &#60;30<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#47;1&#46;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0495"><span class="elsevierStyleSup">34</span></a> A series of 12&#44;508 patients that matched patients according to their eGFR observed no greater risk in those who had been administered IC than in those who were not administered IC&#44; even in the patient group with eGFR &#60;30<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#47;1&#46;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">18</span></a> Therefore&#44; neither the American College of Radiology nor the Royal Australian and New Zealand College of Radiologists consider that there is currently definitive evidence that renal failure constitutes an independent factor for developing CIN&#44; at least when the eGFR is &#62;30<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#47;1&#46;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>&#46;<a class="elsevierStyleCrossRefs" href="#bib0460"><span class="elsevierStyleSup">27&#44;52</span></a></p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Other factors</span><p id="par0055" class="elsevierStylePara elsevierViewall">The other clinical conditions that have been associated with a greater risk of CIN are diabetes mellitus&#44;<a class="elsevierStyleCrossRefs" href="#bib0355"><span class="elsevierStyleSup">6&#44;10&#44;12&#44;24&#44;26</span></a> advanced age&#44;<a class="elsevierStyleCrossRefs" href="#bib0375"><span class="elsevierStyleSup">10&#44;12&#44;24&#44;26</span></a> left ventricular dysfunction&#44;<a class="elsevierStyleCrossRefs" href="#bib0355"><span class="elsevierStyleSup">6&#44;10&#44;12&#44;24&#44;26&#44;45</span></a> anemia<a class="elsevierStyleCrossRefs" href="#bib0375"><span class="elsevierStyleSup">10&#44;24&#44;26</span></a> and in general any condition that can result in a greater risk of developing prerenal renal failure &#40;e&#46;g&#46;&#44; dehydration&#44; arterial hypotension&#44; sepsis&#44; hepatic cirrhosis&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0445"><span class="elsevierStyleSup">24&#44;26</span></a> In contrast to the above&#44; monoclonal gammopathies do not appear to be associated with a greater risk of CIN&#46;<a class="elsevierStyleCrossRef" href="#bib0590"><span class="elsevierStyleSup">53</span></a></p></span></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Concomitant medication</span><p id="par0060" class="elsevierStylePara elsevierViewall">The role played by drugs in the pathogenesis of CIN deserves special mention&#44; given that this is a modifiable factor&#46; The use of any nephrotoxic drug &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41; should be avoided&#44; although there is no conclusive evidence that this type of drug should be withdrawn prior to IC administration&#46;<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">46</span></a> The potential deleterious effect of renin-angiotensin-aldosterone system &#40;RAAS&#41; blockers is controversial&#46; Employing a propensity analysis&#44; a retrospective analysis compared 1322 patients who underwent cardiac catheterization and undergoing treatment with this drug against a control group without treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0595"><span class="elsevierStyleSup">54</span></a> The analysis observed a higher incidence of CIN in the group treated with the RAAS blocker &#40;11&#46;4&#37; vs&#46; 6&#46;3&#37;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0595"><span class="elsevierStyleSup">54</span></a> However&#44; a randomized prospective study with 208 patients with serum creatinine levels &#62;1&#46;7<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#44; 108 of whom had the drug withdrawn before performing cardiac catheterization&#44; could not demonstrate a significant reduction in the risk of CIN &#40;10&#46;9&#37; vs&#46; 18&#46;4&#37;&#59; HR&#44; 0&#46;59&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;16&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0600"><span class="elsevierStyleSup">55</span></a> Although a number of authors have recommended withdrawing angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers prior to cardiac catheterization in patients with CKD&#44;<a class="elsevierStyleCrossRef" href="#bib0605"><span class="elsevierStyleSup">56</span></a> the ESUR guidelines do not consider this withdrawal necessary&#46;<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">46</span></a> Lastly&#44; the classic recommendation of discontinuing metformin before administering IC is not because metformin increases its toxicity but because of the risk that worsening renal function after exposure to IC can result in poisoning by metformin&#44; as well as secondary lactic acidosis&#46;<a class="elsevierStyleCrossRef" href="#bib0460"><span class="elsevierStyleSup">27</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Prevention</span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Limiting exposure</span><p id="par0065" class="elsevierStylePara elsevierViewall">Obviously&#44; the best prevention for CIN is to avoid administering IC when not essential&#44; choosing other diagnostic techniques that do not require IC or postponing the procedure until the patient&#39;s clinical and renal situation are more favorable&#46;<a class="elsevierStyleCrossRef" href="#bib0460"><span class="elsevierStyleSup">27</span></a> If IC administration is essential&#44; the amount of IC should be minimized&#44; maintaining a total dose &#60;4<span class="elsevierStyleHsp" style=""></span>mL&#47;kg &#40;or adjusted to renal function with the following formula&#58; total volume&#47;eGFR &#60;3&#46;4&#41;&#44; and not re-administering within a short period&#46;<a class="elsevierStyleCrossRef" href="#bib0610"><span class="elsevierStyleSup">57</span></a></p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Fluid therapy</span><p id="par0070" class="elsevierStylePara elsevierViewall">Hydration with 0&#46;9&#37; isotonic saline solution before and after the radiological procedure is the main prophylaxis for CIN for patients considered at high risk<a class="elsevierStyleCrossRefs" href="#bib0350"><span class="elsevierStyleSup">5&#44;7&#44;26&#44;27&#44;46&#44;52&#44;57&#8211;59</span></a> &#40;class I recommendation&#44; level of evidence A for the European Society of Cardiology &#91;ESC&#93; guidelines<a class="elsevierStyleCrossRef" href="#bib0610"><span class="elsevierStyleSup">57</span></a> and B for the ESUR guidelines<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">46</span></a>&#41;&#46; However&#44; a recent&#44; randomized&#44; prospective controlled study was conducted with 660 patients with stage III CKD who underwent IC&#44; 328 of whom were treated with prophylaxis based on hydration with 0&#46;9&#37; saline solution&#44; and 332 were not treated with prophylaxis&#46; The study observed no differences in terms of developing CIN &#40;2&#46;6&#37; vs&#46; 2&#46;7&#37;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;471&#41; but did observe an increase in cost and complications due to the development of heart failure in 13 of the 328 patients who underwent volume expansion &#40;compared with none in the no prophylaxis arm&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;0001&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0625"><span class="elsevierStyleSup">60</span></a> This study therefore raises uncertainty as to the relevance of hydration&#44; at least in those patients with eGFR &#62;30<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#47;1&#46;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">There has been discussion in recent years regarding the potential advantages of administering a bicarbonate solution over 0&#46;9&#37; saline solution for preventing CIN&#46; The recently published study PRESERVE attempted to clarify both this aspect and the potential role of acetylcysteine in preventing CIN&#46;<a class="elsevierStyleCrossRef" href="#bib0630"><span class="elsevierStyleSup">61</span></a> PRESERVE was the largest prospective&#44; randomized study to date&#44; with 5177 patients with eGFRs of 15&#8211;59&#46;9<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#47;1&#46;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>&#44; and was unable to demonstrate significant differences between the 2 solutions &#40;0&#46;9&#37; saline solution vs&#46; 1&#46;26&#37; bicarbonate&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0630"><span class="elsevierStyleSup">61</span></a> The main guidelines still consider isotonic saline solution as the reference fluid therapy for preventing CIN&#44;<a class="elsevierStyleCrossRefs" href="#bib0460"><span class="elsevierStyleSup">27&#44;52&#44;57</span></a> although the latest revision of the ESUR guidelines still recommend both solutions interchangeably&#46;<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">46</span></a> The proposed hydration protocols include the infusion of 1&#8211;3<span class="elsevierStyleHsp" style=""></span>mL&#47;kg&#47;h from 1 to 12<span class="elsevierStyleHsp" style=""></span>h before the procedure to 2&#8211;12<span class="elsevierStyleHsp" style=""></span>h afterwards&#44; depending on the patient&#39;s clinical situation and risk of developing heart failure&#46;<a class="elsevierStyleCrossRefs" href="#bib0460"><span class="elsevierStyleSup">27&#44;46&#44;61</span></a> There are more complex protocols aimed at patients who will undergo cardiac catheterization that include administering saline solution at a faster rate &#40;250<span class="elsevierStyleHsp" style=""></span>mL&#47;h&#41; along with a bolus of furosemide<a class="elsevierStyleCrossRef" href="#bib0610"><span class="elsevierStyleSup">57</span></a> or adjusting the fluid infusion according to hemodynamic parameters&#46;<a class="elsevierStyleCrossRef" href="#bib0615"><span class="elsevierStyleSup">58</span></a></p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Drugs</span><p id="par0080" class="elsevierStylePara elsevierViewall">Acetylcysteine has been regularly included in the prophylaxis protocols for CIN in recent years&#44; although its usefulness has been highly controversial&#46;<a class="elsevierStyleCrossRefs" href="#bib0635"><span class="elsevierStyleSup">62&#44;63</span></a> The definitive evidence appears to have arrived with the previously mentioned PRESERVE study&#44; which was unable to demonstrate any protective effect of the antioxidant drug in this context&#46;<a class="elsevierStyleCrossRef" href="#bib0630"><span class="elsevierStyleSup">61</span></a> The most recent guidelines no longer recommend the use of acetylcysteine&#46;<a class="elsevierStyleCrossRefs" href="#bib0460"><span class="elsevierStyleSup">27&#44;46&#44;52&#44;57</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">The use of high-dose statins in a single administration within 24<span class="elsevierStyleHsp" style=""></span>h prior to cardiac catheterization &#40;40&#8211;80<span class="elsevierStyleHsp" style=""></span>mg of atorvastatin or 20&#8211;40<span class="elsevierStyleHsp" style=""></span>mg of rosuvastatin&#41; has recently been related to a lower incidence of CIN&#46;<a class="elsevierStyleCrossRefs" href="#bib0365"><span class="elsevierStyleSup">8&#44;64&#44;65</span></a> High-dose statins have therefore been included in the ESC guidelines &#40;class IIa recommendation and level of evidence A&#41;&#44; although the recent ESUR guidelines consider the evidence still insufficient to recommend high-dose statins&#46;<a class="elsevierStyleCrossRefs" href="#bib0555"><span class="elsevierStyleSup">46&#44;57</span></a> The nephroprotective mechanism of action is related to its pleiotropic effects through a reduced cell apoptosis and reduced IC-induced oxidative stress&#46;<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">8</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">Other tested drugs such as ascorbic acid&#44; theophylline&#44; alprostadil&#44; iloprost and fenoldopam have not provided solid evidence of a beneficial effect and are therefore not recommended&#46;<a class="elsevierStyleCrossRefs" href="#bib0460"><span class="elsevierStyleSup">27&#44;46</span></a></p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Renal replacement therapy</span><p id="par0095" class="elsevierStylePara elsevierViewall">The relatively low molecular weight of current IC agents&#44; their low osmolarity and no protein binding enable excellent elimination through hemodialysis and hemofiltration&#44; although the use of these techniques is not recommended for preventing CIN&#46;<a class="elsevierStyleCrossRefs" href="#bib0455"><span class="elsevierStyleSup">26&#44;27&#44;46&#44;57&#44;59</span></a> Hemodialysis may be considered only for those patients with stage V CKD who have still not started replacement therapy but who already have a vascular access and for whom rapid IC elimination following the procedure could potentially reduce its renal toxicity&#46; In terms of hemofiltration&#44; only the ESC guidelines mention its use before and after cardiac catheterization in complex cases with a high risk of CIN due to advanced CKD &#40;class IIb recommendation with a level of evidence B&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0610"><span class="elsevierStyleSup">57</span></a> Given that IC does not present toxicity other than renal&#44; its administration does not suppose a risk for patients with enuresis undergoing dialysis&#46;<a class="elsevierStyleCrossRefs" href="#bib0460"><span class="elsevierStyleSup">27&#44;46</span></a> Regardless&#44; if there is no emergency&#44; the standard practice is to schedule the radiological procedures with IC before a hemodialysis session with these patients&#46;</p></span></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Conclusions</span><p id="par0100" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">1</span><p id="par0105" class="elsevierStylePara elsevierViewall">The use of the term CIN should be restricted to those cases in which a causal relationship can be demonstrated between the administration of IC and renal impairment&#46; For all others &#40;i&#46;e&#46;&#44; the majority&#41;&#44; the term postcontrast ARF is recommended&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">2</span><p id="par0110" class="elsevierStylePara elsevierViewall">The actual impact of CIN appears lower than previously believed&#44; especially in those cases in which IC administration is performed intravenously and with current usage regimens&#46;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">3</span><p id="par0115" class="elsevierStylePara elsevierViewall">Administering IC to patients with renal failure should be avoided if not essential&#46;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">4</span><p id="par0120" class="elsevierStylePara elsevierViewall">The latest guidelines suggest that administering IC to patients with an eGFR &#62;45<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#47;1&#46;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span> can be considered safe&#46; Below this threshold&#44; the risk of renal toxicity cannot be ruled out&#44; especially in intra-arterial procedures with first-pass renal exposure and in those patients with stage IV-V CKD &#40;eGFR &#60;30<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#47;1&#46;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">5</span><p id="par0125" class="elsevierStylePara elsevierViewall">The risk of renal toxicity should not be the reason for not administering IC if essential at that moment for the patient&#39;s correct diagnosis and treatment&#46;</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">6</span><p id="par0130" class="elsevierStylePara elsevierViewall">To minimize the incidence of CIN&#44; the recommendation is to use the least amount of iso-osmolar or low-osmolar IC possible &#40;any&#44; with the possible exception of iohexol&#41; and ensure the patient&#39;s adequate hydration with isotonic saline solution if there is no risk of heart failure&#46;</p></li></ul></p></span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Case resolution</span><p id="par0135" class="elsevierStylePara elsevierViewall">Caso no&#46; 1 Faced with a low risk of CIN due to the patient&#39;s baseline renal function and an absence of concomitant prerenal factors&#44; CT was performed without prophylactic measures with 100<span class="elsevierStyleHsp" style=""></span>mL of iodixanol&#59; renal function remained stable during the follow-up&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">Caso no&#46; 2 The patient was considered at risk for developing CIN&#46; Therefore&#44; once the patient&#39;s heart failure was compensated&#44; an infusion of 1&#46;5<span class="elsevierStyleHsp" style=""></span>mL&#47;k&#47;h of 0&#46;9&#37; isotonic saline solution was administered from 6<span class="elsevierStyleHsp" style=""></span>h before the catheterization to 6<span class="elsevierStyleHsp" style=""></span>h after the procedure&#44; and an 80-mg dose of atorvastatin was administered 12<span class="elsevierStyleHsp" style=""></span>h before the procedure&#46; The procedure was performed while minimizing the IC dose &#40;60<span class="elsevierStyleHsp" style=""></span>mL of iodixanol&#41;&#46; A laboratory check 72<span class="elsevierStyleHsp" style=""></span>h later confirmed the stability of the creatinine values&#46;</p></span><span id="sec0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Conflicts of interest</span><p id="par0145" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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                  "titulo" => "Iodinated contrast type and dose"
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          "titulo" => "Prevention"
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              "identificador" => "sec0090"
              "titulo" => "Drugs"
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              "identificador" => "sec0095"
              "titulo" => "Renal replacement therapy"
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          "clase" => "keyword"
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            0 => "Contrast-induced nephropathy"
            1 => "Post-contrast acute renal failure"
            2 => "Chronic kidney disease"
            3 => "Iodinated contrast"
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            0 => "Nefropat&#237;a inducida por contraste"
            1 => "Fracaso renal agudo poscontraste"
            2 => "Enfermedad renal cr&#243;nica"
            3 => "Contraste iodado"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The use of iodinated contrast media can cause renal toxicity&#46; Whether contrast media are exclusively responsible for kidney damage is currently the subject of debate&#44; given that in most cases&#44; other potential causes of the renal failure are present&#46; With current low-osmolar and iso-osmolar contrast media&#44; the incidence rate of contrast-induced nephropathy is estimated to be &#60;1&#37; in the low-risk population but can increase to 37&#37; in patients who are administered contrast by an intra-arterial administration and&#47;or who have renal failure with an estimated glomerular filtration rate &#40;eGFR&#41; &#60;30<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#47;1&#46;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>&#46; To minimize the risk of renal toxicity&#44; the recommendation is to administer the least amount of contrast possible and ensure appropriate volume expansion by infusing 0&#46;9&#37; saline solution&#46;</p></span>"
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        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">El uso de contrastes iodados puede causar nefrotoxicidad&#46; Actualmente se cuestiona que los contrastes sean los responsables exclusivos del da&#241;o renal&#44; ya que en la mayor&#237;a de los casos coexisten otras causas potenciales de fracaso renal&#46; Con los contrastes actuales de baja osmolaridad e isoosmolares&#44; la incidencia de nefropat&#237;a por contraste se estima que es inferior al 1&#37; en la poblaci&#243;n de bajo riesgo&#59; pero puede incrementarse hasta el 37&#37; en pacientes que reciben contraste por v&#237;a intraarterial y&#47;o que presentan insuficiencia renal con filtrado glomerular estimado inferior a 30<span class="elsevierStyleHsp" style=""></span>ml&#47;min&#47;1&#46;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>&#46; Para minimizar el riesgo de nefrotoxicidad se recomienda administrar la menor cantidad posible de contraste y asegurar una adecuada expansi&#243;n de volumen mediante la infusi&#243;n de soluci&#243;n salina 0&#44;9&#37;&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Mu&#241;oz de Bustillo Llorente E&#44; de Miguel Balsa E&#46; Nefropat&#237;a inducida por contrastes iodados radiol&#243;gicos&#46; Rev Cl&#237;n Esp&#46; 2018&#46; <span class="elsevierStyleInterRef" id="intr0005" href="https://doi.org/10.1016/j.rce.2018.09.004">https&#58;&#47;&#47;doi&#46;org&#47;10&#46;1016&#47;j&#46;rce&#46;2018&#46;09&#46;004</span></p>"
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          "leyenda" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Abbreviations&#58; NSAIDs&#44; anti-inflammatory nonsteroidal drugs&#59; CKD-EPI&#44; Chronic Kidney Disease Epidemiology Collaboration&#59; eGFR&#44; estimated glomerular filtration rate&#59; RAAS&#44; renin-angiotensin-aldosterone system&#46;</p>"
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                  \t\t\t\t\tvoid\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Risk factors&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Prevention&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Monitoring&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Procedure-related</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " rowspan="2" align="left" valign="\n
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                  \t\t\t\t">Use iso-osmolar or low-osmolar contrast &#40;except iohexol&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Determine baseline renal function &#40;eGFR CKD-EPI&#41;</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Greater risk by intra-arterial pathway than by intravenous&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Contrast 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">Administer minimum effective doses of contrast &#40;&#60;4<span class="elsevierStyleHsp" style=""></span>mL&#47;kg or volume&#47;eGFR &#60;3&#46;4&#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
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                  \t\t\t\t">If baseline eGFR is &#60;45<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#47;1&#46;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>&#44; perform a check at 72<span class="elsevierStyleHsp" style=""></span>h&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Patient-related</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " rowspan="2" align="left" valign="\n
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                  \t\t\t\t">Administer intravenous hydration with 1&#8211;3<span class="elsevierStyleHsp" style=""></span>mL&#47;kg&#47;h of 0&#46;9&#37; saline serum from 1 to 12<span class="elsevierStyleHsp" style=""></span>h before the procedure to 2&#8211;12<span class="elsevierStyleHsp" style=""></span>h after the procedure&#46;</td><td class="td" title="\n
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                  \t\t\t\t">If the eGFR drops at 72<span class="elsevierStyleHsp" style=""></span>h&#44; repeat the measurement at 14 days</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Renal failure &#40;eGFR &#60;45<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#47;1&#46;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Diabetes mellitus&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Administer 40&#8211;80<span class="elsevierStyleHsp" style=""></span>mg of atorvastatin or 20&#8211;40<span class="elsevierStyleHsp" style=""></span>mg of rosuvastatin in a single dose 12<span class="elsevierStyleHsp" style=""></span>h before a cardiac catheterization&#63;&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
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Left ventricle dysfunction&nbsp;\t\t\t\t\t\t\n
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                  \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
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Anemia&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \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></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Advanced age&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \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
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Prerenal factors&#58; sepsis&#44; hypotension&#44; dehydration&#44; hepatic cirrhosis&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
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                  \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></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Drugs</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \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
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>NSAIDs&#44; aminoglycosides&#44; amphotericin B&#44; acyclovir&#44; foscarnet&#44; anticalcineurin agents&#44; cis-platinum&#46;&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="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>RAAS blockers&#63;&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="" 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></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>High-dose diuretics&#63;&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
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                  \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
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Predisposing factors for developing iodinated contrast-induced nephropathy and prevention and monitoring measures for patients at risk&#46;</p>"
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      "titulo" => "References"
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        0 => array:2 [
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                            0 => "G&#46;J&#46; Merten"
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                            2 => "L&#46;V&#46; Gray"
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                          "etal" => true
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Article information

ISSN: 22548874
Original language: English

DOI:10.1016/j.rceng.2018.09.002

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