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In an analysis of more than 65&#44;000 patients with HF with reduced EF and preserved EF of the Acute Decompensated Heart Failure National Registry &#40;ADHERE&#41;&#44; a blood urea nitrogen &#40;BUN&#41; level on admission &#62;43<span class="elsevierStyleHsp" style=""></span>mg&#47;dL was the most powerful predictor of hospital mortality&#46;<a class="elsevierStyleCrossRef" href="#bib0665"><span class="elsevierStyleSup">5</span></a> Therefore&#44; the quantification of renal function with simple&#44; regularly used parameters helps stratify patients with acute and chronic HF&#44; regardless of their EF&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">The kidneys are structurally and functionally complex organs that&#44; in order to maintain the homeostasis of the internal environment&#44; require the integration of glomerular function&#44; mesangial activity&#44; sphincter tone and glomerular and peritubular capillaries&#44; and the tubular excretory and resorptive function&#46; Most of these structures produce substances &#40;biomarkers&#41; that are measurable in blood or urine&#44; which provide more or less precise information on their operation or impairment&#46;<a class="elsevierStyleCrossRefs" href="#bib0670"><span class="elsevierStyleSup">6&#44;7</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">In practice&#44; we often talk of renal &#8220;dysfunction&#8221; or &#8220;insufficiency&#8221; when referring to a decline in eGFR&#46; Due to the fact that this entails an excessive simplification in the context of HF&#44; it is worth clarifying four concepts&#58;</p><p id="par0030" class="elsevierStylePara elsevierViewall">&#40;1&#41; <span class="elsevierStyleItalic">Renal failure</span> &#40;RF&#41;&#58; This term refers to a persistent and stable reduction of eGFR in the short or long term&#46; In this article&#44; we follow the gradation in stages of the Kidney Disease Improving Global Outcomes &#40;KDIGO&#41; guidelines<a class="elsevierStyleCrossRef" href="#bib0680"><span class="elsevierStyleSup">8</span></a> and the subsequent implementation of various Spanish scientific societies &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0685"><span class="elsevierStyleSup">9</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">For a proper understanding of the following two categories&#44; the variable &#8220;time&#8221; must be included in its definition&#44; differentiating the changes in renal function that occur rapidly from those that occur over more prolonged periods&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">&#40;2&#41; <span class="elsevierStyleItalic">Worsening renal function</span> &#40;WRF&#41;&#58; According to the criteria proposed by Damman and Testani&#44;<a class="elsevierStyleCrossRefs" href="#bib0645"><span class="elsevierStyleSup">1&#44;10</span></a> WRF is considered when serum creatinine levels increase by &#8805;0&#46;3<span class="elsevierStyleHsp" style=""></span>mg&#47;dL or 25&#37; compared with baseline or when the eGFR decreases by &#8805;20&#37; in within 1 to 26 weeks&#44; in patients with chronic HF &#40;i&#46;e&#46;&#44; without abrupt changes in their functional class or hemodynamic condition&#41;&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">&#40;3&#41; Acute renal damage &#40;ARD&#41;&#58; ARD is considered present in patients with AHF when baseline serum creatinine levels increase between 1&#46;5 and 1&#46;9 times the previous value during hospitalization or the week before hospitalization or when serum creatinine levels increase &#8805;0&#46;3<span class="elsevierStyleHsp" style=""></span>mg&#47;dL in 48<span class="elsevierStyleHsp" style=""></span>h or the diuresis decreases &#60;0&#46;5<span class="elsevierStyleHsp" style=""></span>mL&#47;kg&#47;h within 6&#8211;12<span class="elsevierStyleHsp" style=""></span>h&#46;<a class="elsevierStyleCrossRefs" href="#bib0645"><span class="elsevierStyleSup">1&#44;10</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">These three categories are not in any way impermeable compartments&#46; On the contrary&#44; patients can often have a certain degree of RF prior to a deteriorating renal function that&#44; depending on the temporal framework in which it occurs&#44; leads to a WRF or to ARD&#46; The introduction of this progression criterion adds a fundamental nuance to understanding the complex relationship between the heart and kidneys in HF&#44; which is the patient&#39;s degree of clinical or functional stability&#46;<a class="elsevierStyleCrossRefs" href="#bib0645"><span class="elsevierStyleSup">1&#44;10</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">&#40;4&#41; <span class="elsevierStyleItalic">Acute tubular damage</span>&#58; This involves a poorly characterized concept&#44; which could be defined as any aggression to the tubulointerstitial structures that does not affect the eGFR&#46; To diagnose this condition&#44; the measurement in blood or urine of various molecules produced in the renal tubules has been proposed&#44; whose expression or synthesis is modified in these circumstances &#40;<a class="elsevierStyleCrossRefs" href="#fig0005">Figs&#46; 1 and 2</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0695"><span class="elsevierStyleSup">11</span></a> These include neutral gelatinase-associated lipocalin &#40;NGAL&#41;&#44; kidney injury molecule-1 &#40;KIM-1&#41;&#44; interleukin-18 &#40;IL-18&#41; and N-acetyl-&#946;-<span class="elsevierStyleSmallCaps">d</span>-glucosaminidase &#40;NAG&#41;&#46; Studies conducted in various contexts of HF&#44; in which the kidney aggression was well characterized &#40;aortocoronary bypass&#44; nephrotoxic radiological contrast media&#44; sepsis&#44; etc&#46;&#41;&#44; have demonstrated the capacity of these substances to diagnose ARD and its prognostic value&#46;<a class="elsevierStyleCrossRefs" href="#bib0700"><span class="elsevierStyleSup">12&#8211;15</span></a> Based on these studies&#44; the performance in HF was assumed to be similar&#46; However&#44; a critical literature review in the specific setting of HF revealed numerous contradictions&#46; In a highly schematic manner&#44; we could conclude that the usefulness of the tubular biomarkers in predicting WRF or ARD is questionable&#44; although an increase in their concentrations correlates&#44; in general&#44; with a poorer vital prognosis&#46;<a class="elsevierStyleCrossRef" href="#bib0710"><span class="elsevierStyleSup">14</span></a></p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Cardiorenal syndrome versus cardiorenal interaction</span><p id="par0060" class="elsevierStylePara elsevierViewall">Ronco et al&#46; systematized &#40;in a simple and didactic manner&#41; the potential interrelationships between the heart and kidneys when either is affected acutely or chronically&#46;<a class="elsevierStyleCrossRef" href="#bib0720"><span class="elsevierStyleSup">16</span></a> The authors proposed 5 clinical forms&#44; which they called &#8220;cardiorenal syndrome&#8221; &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; However&#44; a careful reading of this study shows that most of the assertions on which this classification was based come from the consensus of experts and&#44; in reality&#44; lack solid experimental and clinical evidence&#46; The prognostic significance of each of the subtypes has not been demonstrated&#44; and numerous pathophysiological mechanisms that are alleged are speculative&#46;<a class="elsevierStyleCrossRef" href="#bib0645"><span class="elsevierStyleSup">1</span></a> Clinical practice itself calls into question their actual usefulness&#46; In fact&#44; in patients with decompensated HF and high creatinine and urea levels&#44; it is very difficult to differentiate between type 1 and type 3 cardiorenal syndrome&#44; even a type 4 if the dyspnea is not highly pronounced&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">There are also other indications that call into question the cardiorenal syndrome as an entity&#46; Firstly&#44; the prognosis does not always worsen when urea and creatinine levels increase in HF&#46; This is the case during titration of renin&#8211;angiotensin&#8211;aldosterone system blockers<a class="elsevierStyleCrossRef" href="#bib0725"><span class="elsevierStyleSup">17</span></a> and in the context of effective treatment of AHF&#44; in which moderate creatinine level increases have no adverse meaning&#44; especially if accompanied by clinical improvement and reduced congestive symptoms&#46;<a class="elsevierStyleCrossRef" href="#bib0730"><span class="elsevierStyleSup">18</span></a> These conditions have been labeled &#8220;pseudo&#8221; WRF or ARD&#44; as opposed to true WRF&#46;<a class="elsevierStyleCrossRef" href="#bib0735"><span class="elsevierStyleSup">19</span></a> Moreover&#44; the predisposition to complications during episodes of cardiac decompensation do not depend exclusively on the patient&#39;s baseline eGFR&#46; In a retrospective study on 908 patients discharged after a decompensated HF episode&#44; Testani et al&#46; identified a special risk subgroup&#44; with a 2-fold greater mortality&#44; consisting of patients with a baseline eGFR<span class="elsevierStyleHsp" style=""></span>&#60;60<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#47;1&#46;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span> along with a greater than mean brain natriuretic peptide &#40;BNP&#41; concentration &#40;1296<span class="elsevierStyleHsp" style=""></span>pg&#47;mL&#41; and a BUN&#47;creatinine ratio<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>17&#46;<a class="elsevierStyleCrossRef" href="#bib0740"><span class="elsevierStyleSup">20</span></a> A low baseline eGFR by itself does not confer a significant risk of mortality&#46; The authors&#8217; interpretation was that there are &#8220;phenotypes&#8221; that are especially susceptible to complications&#44; patients who already have established renal function impairment and who experience a greater degree of cardiac and renal stress&#44; reflected in the BNP concentrations and BUN&#47;creatinine ratio&#44; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0740"><span class="elsevierStyleSup">20</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">Consequently and although the term is less precise&#44; it would be preferable to use the term &#8220;cardiorenal interaction&#8221; rather than &#8220;cardiorenal syndrome&#8221; to refer to the relationship&#44; with pathophysiological links between the heart and kidneys in the context of HF&#46; The mediators of cardiorenal damage&#44; which are still not well understood&#44; include splanchnic area congestion&#44;<a class="elsevierStyleCrossRefs" href="#bib0745"><span class="elsevierStyleSup">21&#44;22</span></a> the increase in intraabdominal pressure &#40;responsible in turn for renal congestion&#41;&#44;<a class="elsevierStyleCrossRefs" href="#bib0755"><span class="elsevierStyleSup">23&#44;24</span></a> the rate of blood volume replenishment from the interstitial space&#44;<a class="elsevierStyleCrossRefs" href="#bib0765"><span class="elsevierStyleSup">25&#44;26</span></a> renal hypoperfusion&#44;<a class="elsevierStyleCrossRef" href="#bib0775"><span class="elsevierStyleSup">27</span></a> various inflammatory mechanisms<a class="elsevierStyleCrossRef" href="#bib0780"><span class="elsevierStyleSup">28</span></a> and endothelial dysfunction&#46;<a class="elsevierStyleCrossRef" href="#bib0785"><span class="elsevierStyleSup">29</span></a></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Prognostic value of renal dysfunction in heart failure</span><p id="par0075" class="elsevierStylePara elsevierViewall">In the general population&#44; eGFR decreases 0&#46;5&#8211;1<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#47;1&#46;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>&#47;year&#44;<a class="elsevierStyleCrossRefs" href="#bib0790"><span class="elsevierStyleSup">30&#44;31</span></a> while in patients with chronic kidney disease &#40;CKD&#41; this rate can be 4-fold greater&#46;<a class="elsevierStyleCrossRefs" href="#bib0800"><span class="elsevierStyleSup">32&#44;33</span></a> A meta-analysis included 18&#44;634 patients with HF &#40;hospitalized and outpatient&#41; <span class="elsevierStyleItalic">with the objective of determining the incidence and prognostic meaning of WRF in the HF</span>&#46; The meta-analysis found that WRF occurs in 25&#37; of cases and increases the risk of death by 60&#37; &#40;odds ratio &#91;OR&#93;&#44; 1&#46;62&#59; 95&#37; CI 1&#46;45&#8211;1&#46;82&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0810"><span class="elsevierStyleSup">34</span></a> In this study&#44; the WRF criterion differed from that described earlier&#44; given that WRF was considered an increase in serum creatinine levels &#62;0&#46;2<span class="elsevierStyleHsp" style=""></span>mg&#47;dL or a decrease in eGFR of at least 5<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#47;1&#46;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>&#46; Although the pathophysiology of WRF is different in patients with acute and chronic HF and both groups were analyzed separately in the meta-analysis&#44; the prognostic significance of WRF was similar in both groups&#46; The meta-analysis also observed a linear relationship between baseline eGFR and the probability of developing WRF&#59; i&#46;e&#46;&#44; renal dysfunction is a risk factor for greater functional impairment as the HF becomes more acute or progresses&#46; A second finding of interest resulting from the previous was that the risk of complications associated with WRF was better estimated in relative terms of percentage reduction in eGFR than by using absolute values&#44; and always taking into account the baseline eGFR values&#46; For example&#44; the consequences of an eGFR reduction of 6<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#47;1&#46;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span> in a patient with a baseline eGFR of 25<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#47;1&#46;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span> are more severe that for a patient whose baseline eGFR is 60<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 third important aspect was that the relationship between the increase in serum creatinine concentrations and the increased risk of complications does not follow a linear distribution but rather an exponential one&#46; In fact&#44; a certain threshold effect has been detected&#44; with an exponential increase in the risk of complications when the serum creatinine level increases more than 0&#46;5<span class="elsevierStyleHsp" style=""></span>mg&#47;dL above the normal limit&#44; which is equivalent to an eGFR reduction of 15<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="par0080" class="elsevierStylePara elsevierViewall">In a subsequent meta-analysis&#44; the authors analyzed the risk of death in patients with HF in relation to the presence of baseline CKD or with the development of WRF&#46; The authors analyzed 1&#44;076&#44;104 patients &#40;57 studies&#41; with HF and baseline CKD and 49&#44;890 patients &#40;28 studies&#41; with HF who developed WRF&#46; The prevalence rate of CKD in patients with HF was 32&#37; and was associated with an almost 2-fold increase in the risk of all-cause death compared with the patients with normal renal function &#40;OR 2&#46;34&#44; 95&#37; CI 2&#46;20&#8211;2&#46;50&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0815"><span class="elsevierStyleSup">35</span></a> The WRF &#40;with somewhat different definition criteria&#41; among the patients with HF had a prevalence rate of 23&#37; and practically doubled the risk of mortality &#40;OR 1&#46;81&#44; 95&#37; CI 1&#46;55&#8211;2&#46;12&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">As a result&#44; both CKD and WRF are common in patients with chronic HF and during decompensations&#44; and its presence entails a poorer vital prognosis and increased risk of complications&#46; In other words&#44; their detection and follow-up are important when stratifying the risk and planning the treatment of patients with HF&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Prognostic biomarkers in renal function</span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Chronic heart failure</span><p id="par0090" class="elsevierStylePara elsevierViewall">In patients with stable chronic HF&#44; sustained renal function over time is a predictor of a good prognosis&#46; However&#44; the best method for measuring this function has not been defined&#46; Classically&#44; serum creatinine<a class="elsevierStyleCrossRef" href="#bib0820"><span class="elsevierStyleSup">36</span></a> and&#44; more recently&#44; cystatin C<a class="elsevierStyleCrossRef" href="#bib0825"><span class="elsevierStyleSup">37</span></a> &#40;CysC&#41; levels have been employed&#46; Both are glomerular filtration metabolites that undergo practically no changes by tubular reabsorption or excretion&#46; Nevertheless&#44; serum creatinine concentrations are highly dependent on exogenous factors&#44; especially muscle mass&#44; protein intake and sex&#44; which impedes the interpretation of their results&#46; In fact&#44; the relationship between eGFR and serum creatinine follows a &#8220;J&#8221; curve&#44; which underestimates the risk of death for patients with low creatinine concentrations due to severe consumptive diseases such as HF&#46;<a class="elsevierStyleCrossRef" href="#bib0830"><span class="elsevierStyleSup">38</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">CysC concentrations are much more stable and independent&#44; due to their own biology&#44; size and electrical charge&#44; which makes them an ideal candidate for determining the eGFR&#46; However&#44; the serum concentrations and normality cutoffs&#44; although standardized&#44; are not regularly used in hospitals&#44; and their measurement is not available in all laboratories&#46;<a class="elsevierStyleCrossRef" href="#bib0835"><span class="elsevierStyleSup">39</span></a> The gold standard for assessing glomerular function is based on the measurement of inulin clearance<a class="elsevierStyleCrossRef" href="#bib0840"><span class="elsevierStyleSup">40</span></a> or iothalamate clearance&#44;<a class="elsevierStyleCrossRef" href="#bib0845"><span class="elsevierStyleSup">41</span></a> a measurement not possible in the daily routine&#46; The easiest and most useful of using creatinine or CysC concentrations is the use of formulas for determining the EGFR&#46;<a class="elsevierStyleCrossRefs" href="#bib0850"><span class="elsevierStyleSup">42&#44;43</span></a> Thus&#44; the influence of confounding factors is reduced&#44; and the uncertainty is removed of using concentrations with poorly standardized thresholds&#46; There are numerous formulas for determining the eGFR&#46; The most widely used until a few years ago were the Cockcroft-Gault formula<a class="elsevierStyleCrossRef" href="#bib0860"><span class="elsevierStyleSup">44</span></a> and the Modification of Diet in Renal Disease &#40;MDRD&#41; formula&#44; especially the simplified version that includes 4 parameters &#40;MDRD-4&#41;&#44; whose prognostic value prognosis has been well demonstrated&#46;<a class="elsevierStyleCrossRefs" href="#bib0855"><span class="elsevierStyleSup">43&#44;45&#44;46</span></a> The Cockcroft&#8211;Gault formula stopped being used at the start of 2000 because studies that supported its use were based on nonstandardized creatinine measurements&#46;<a class="elsevierStyleCrossRef" href="#bib0680"><span class="elsevierStyleSup">8</span></a> For patients with mild degrees of renal dysfunction &#40;eGFR slightly lower than 60<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#47;1&#46;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>&#41;&#44; the formula&#39;s performance is poorer&#46; Other formulas have therefore been proposed&#44; such as the Chronic Kidney Disease Epidemiology Collaboration &#40;CKD-EPI&#41; equation&#44; in which correction coefficients are applied for the 4 variables employed in the MDRD&#44; which improve the eGFR calculation in the general population and in chronic stable HF&#46;<a class="elsevierStyleCrossRefs" href="#bib0875"><span class="elsevierStyleSup">47&#8211;49</span></a> The inclusion of CysC in the formulas allows for a prognostic reclassification of up to 22&#37;&#44;<a class="elsevierStyleCrossRef" href="#bib0890"><span class="elsevierStyleSup">50</span></a> with better performance among patients with HF and reduced EF<a class="elsevierStyleCrossRef" href="#bib0895"><span class="elsevierStyleSup">51</span></a> and with slight eGFR reduction&#46;<a class="elsevierStyleCrossRefs" href="#bib0900"><span class="elsevierStyleSup">52&#44;53</span></a> The minor influence of exogenous factors on serum CysC concentrations is responsible for the greater performance of the eGFR calculation formulas based on this protein&#46; Provided the eGFR is calculated based on the creatinine concentration&#44; the relationship between the prognosis and the eGFR assumes a &#8220;J&#8221; shape&#46; This is due to the fact that some patients with low serum creatinine concentrations &#40;and therefore apparently normal renal function&#41; have in fact severe diseases&#44; accompanied by muscle wasting&#44; which have poor prognoses&#46; This phenomenon disappears when using CysC because its concentration is not virtually unaffected by any exogenous factor&#44;<a class="elsevierStyleCrossRef" href="#bib0910"><span class="elsevierStyleSup">54</span></a> and its relationship with eGFR and&#44; accordingly&#44; with the prognosis is linear&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Acute heart failure</span><p id="par0100" class="elsevierStylePara elsevierViewall">Renal function assessment during cardiac decompensations has a number of peculiarities that require the interpretation of changes in renal biomarker concentrations along with the clinical situation and treatment response&#46; The useful renal dysfunction biomarkers during HF exacerbations are&#44; equally&#44; the formulas for calculating GFR and urea or BUN&#46; Creatinine concentrations are also a prognostic determinant in AHF&#46; In fact&#44; changes in creatinine concentration define ARD&#46; However&#44; its limitations are numerous&#44; and there are more reliable alternatives in the prognostic stratification&#46; For example&#44; an isolated serum CysC concentration reading during hospitalization for HF decompensation has a prognostic value independent of EF&#44; with a variable cutoff in the various studies of approximately 1&#46;24&#8211;1&#46;29<span class="elsevierStyleHsp" style=""></span>mg&#47;L&#44; thereby indicating poorer HF the higher the concentration&#46;<a class="elsevierStyleCrossRefs" href="#bib0915"><span class="elsevierStyleSup">55&#8211;60</span></a> CysC also provides complementary and independent information from that provided by NT-proBNP concentrations&#46;<a class="elsevierStyleCrossRefs" href="#bib0930"><span class="elsevierStyleSup">58&#44;59</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">The formulas for calculating GFR &#40;MDRD<a class="elsevierStyleCrossRefs" href="#bib0865"><span class="elsevierStyleSup">45&#44;46&#44;61&#44;62</span></a> and CKD-EPI<a class="elsevierStyleCrossRefs" href="#bib0955"><span class="elsevierStyleSup">63&#44;64</span></a>&#41; are also useful for AHF&#44; regardless of the EF&#46; According to a HF registry study &#40;RICA Registry&#41; of the Spanish Society of Internal Medicine &#40;SEMI&#41;&#44; the CKD-EPI-creatinine formula is more accurate than MDRD for patients with HF and preserved EF&#46;<a class="elsevierStyleCrossRef" href="#bib0950"><span class="elsevierStyleSup">62</span></a> Nevertheless&#44; due to the lack of availability of CysC&#44; the performance of the CKD-EPI formula based on CysC or creatinine could not be directly compared&#46;<a class="elsevierStyleCrossRef" href="#bib0950"><span class="elsevierStyleSup">62</span></a> The CKD-EPI-CysC formula improved the results that only included creatinine&#44; because it entails a reclassification of up to 44&#37; in the prediction of all-cause mortality and is especially sensitive in patients with mild WRF&#46;<a class="elsevierStyleCrossRefs" href="#bib0920"><span class="elsevierStyleSup">56&#44;59</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">For patients hospitalized for AHF&#44; the serum urea and BUN concentrations are independent predictors of hospital mortality<a class="elsevierStyleCrossRefs" href="#bib0665"><span class="elsevierStyleSup">5&#44;65&#44;66</span></a> in the short term &#40;1 month&#41;<a class="elsevierStyleCrossRefs" href="#bib0975"><span class="elsevierStyleSup">67&#8211;69</span></a> and long term &#40;1 year&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0970"><span class="elsevierStyleSup">66&#44;70&#8211;73</span></a> In our experience&#44;<a class="elsevierStyleCrossRef" href="#bib0985"><span class="elsevierStyleSup">69</span></a> a urea concentration at admission &#62;66<span class="elsevierStyleHsp" style=""></span>mg&#47;dL identifies a patient subgroup with a 3-fold greater risk of death in the month after the discharge&#44; a period of special vulnerability for patients with comorbidities&#44; such as patients with HF&#46;<a class="elsevierStyleCrossRef" href="#bib1010"><span class="elsevierStyleSup">74</span></a> Having such an inexpensive biomarker such as urea can help define healthcare circuits and anticipate the follow-up needs after a discharge for a HF exacerbation&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">It has been postulated that the urea concentration in AHF episodes offers relevant information on renal function &#40;eGFR&#41;&#44; tubular reabsorption that reduces the urea excretion in urine &#40;which in turn is a reflection of the renin&#8211;angiotensin system activation&#44; the sympathetic system and vasopressin&#41;&#44; and hypercatabolism&#44; which affects patients with exacerbated HF&#46;<a class="elsevierStyleCrossRefs" href="#bib0995"><span class="elsevierStyleSup">71&#44;75&#44;76</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">The increase in the BUN&#47;creatinine ratio also has prognostic value for patients with AHF as a predictor of greater mortality<a class="elsevierStyleCrossRefs" href="#bib1025"><span class="elsevierStyleSup">77&#44;78</span></a> and WRF&#46;<a class="elsevierStyleCrossRefs" href="#bib1035"><span class="elsevierStyleSup">79&#44;80</span></a> One study correlated this increase with the degree of systemic congestion&#46;<a class="elsevierStyleCrossRef" href="#bib1045"><span class="elsevierStyleSup">81</span></a> Nevertheless&#44; the cutoffs are poorly defined because the studies listed above always referred to higher percentiles of the ratio&#44; and therefore their usefulness in clinical practice is only for guidance&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Biomarkers sensitive to tubular damage</span><p id="par0125" class="elsevierStylePara elsevierViewall">This section reviews the role of a number of biomarkers that were presumed to have high diagnostic and prognostic performance and whose use both in the specific clinical context of HF and in research provided results that were difficult to interpret and apparently contradictory&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">To understand the usefulness of these new biomarkers&#44; we need to understand their biological and molecular characteristics and their participation in the pathophysiology and place them in the appropriate clinical context&#46; Given that this new category contains many biomarkers&#44;<a class="elsevierStyleCrossRefs" href="#bib1050"><span class="elsevierStyleSup">82&#8211;84</span></a> we will discuss the most widely studied ones&#44; especially NGAL<a class="elsevierStyleCrossRefs" href="#bib1050"><span class="elsevierStyleSup">82&#44;83&#44;85</span></a> and KIM-1&#46;<a class="elsevierStyleCrossRefs" href="#bib1070"><span class="elsevierStyleSup">86&#8211;88</span></a> More detailed information<a class="elsevierStyleCrossRef" href="#bib1085"><span class="elsevierStyleSup">89</span></a> and the corresponding supporting documentation are indicated in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46;<a class="elsevierStyleCrossRefs" href="#bib0710"><span class="elsevierStyleSup">14&#44;90&#8211;128</span></a></p><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Neutrophil gelatinase-associated lipocalin</span><p id="par0135" class="elsevierStylePara elsevierViewall">This protein has 178 amino acids and 25-kDa and belongs to the lipocalin family&#44; members of which get their name from their calyx structure&#46; NGAL physiologically intervenes in the immune modulation&#44; inflammation and transformation of neoplastic cells&#46; NGAL can sequester iron in the intracellular medium &#40;siderophilin&#41; to decrease the potential &#8220;redox&#8221; and limit the damage caused by free radicals generated in inflammatory processes&#46; NGAL is a ubiquitous protein&#44; produced by immature neutrophils and epithelial cells in the lung&#44; proximal kidney tubule&#44; trachea&#44; stomach and colon&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">Due to its small molecular size&#44; NGAL is freely filtered in the glomerulus and completely reabsorbed in the tubules&#46; NGAL exists in the form of monomers and dimers and can be measured in blood and urine&#46; Blood NGAL concentrations can increase a thousand fold in cases of ARD and are therefore more related to inflammatory activation than to the renal dysfunction&#46; It is likely that the measurement of urinary NGAL is more specific as a biomarker of ARD&#46; Perhaps due to its different origin&#44; there is no good correlation between serum and urinary NGAL concentrations&#46; In conclusion&#44; due to its low specificity and dependence on GF&#44; serum NGAL concentrations as a biomarker of ARD should be interpreted with caution in the context of HF &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Kidney injury molecule-1</span><p id="par0145" class="elsevierStylePara elsevierViewall">KIM-1 is a type 1 transmembrane glycoprotein with an ectodomain that contains 6 cysteine residues and a structure related to the immunoglobulins&#44; along with 2 points of N-glycosylation and a domain rich in threonine or serine and proline&#44; characteristic of mucin-like proteins&#46;<a class="elsevierStyleCrossRefs" href="#bib1050"><span class="elsevierStyleSup">82&#44;83&#44;85</span></a> KIM-1 also has a transmembrane domain and a relatively short cytoplasmic domain&#44; with a highly preserved motif for the phosphorylation by the kinase protein&#44; in keeping with its function as a signaling molecule&#46; KIM-1 is physiologically related to immunomodulation in general&#46; In physiological conditions&#44; the KIM-1 molecule has virtually no renal expression&#46; When faced with any aggression&#44; KIM-1 is expressed in the luminal pole of the cells of the proximal renal tubular epithelium as a marker of cell dedifferentiation and proliferation&#46; KIM-1 has been attributed a key role in the regeneration of the renal tubular epithelium after aggressions of any type&#44; modulating the immune response and facilitating the phagocytosis of apoptotic particles&#46; KIM-1 concentrations are determined only in urine and have been seldom studied in the specific context of HF&#44; although an increase in its concentration has been associated with excess mortality and readmissions &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">Given the physiological functions of KIM-1&#44; related to the regeneration of the renal tubular epithelium&#44; <span class="elsevierStyleItalic">it would be logical to expect that this molecule would be exclusively expressed in conditions of tubular involvement&#44; and therefore that its concentrations increase in urine when there is aggression to this epithelium&#46;</span> However&#44; there are three studies with surprising results&#46; These studies included large cohorts of 2948&#44;<a class="elsevierStyleCrossRef" href="#bib1060"><span class="elsevierStyleSup">84</span></a> 2917<a class="elsevierStyleCrossRef" href="#bib1075"><span class="elsevierStyleSup">87</span></a> and 565<a class="elsevierStyleCrossRef" href="#bib1080"><span class="elsevierStyleSup">88</span></a> outpatients with no clinically apparent kidney or cardiovascular disease who were followed-up over a long period&#46; The highest KIM-1 urinary concentrations were predictive of the development of HF&#46; The explanation for this unknown phenomenon must contain important keys to understanding the complex pathophysiological relationship between the heart and kidneys&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">The few published studies on the performance of tubular biomarkers in HF have had heterogeneous designs and generally small sample sizes&#44; which explains why the results have varied significantly and are difficult to interpret &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; In summary&#44; we can state that biomarkers of tubular damage used in HF have failed to predict WRF and ARD and only some are predictors of long-term mortality&#46; There are several reasons for this behavior&#46; The pathophysiology of the cardiorenal interaction&#44; both in chronic HF and in exacerbations&#44; is complex and only partially known&#46; The WRF and ARD criteria&#44; although agreed upon and widely accepted&#44; have been conceived from a nephrology perspective and should be adapted to the specific context of HF&#44; in which the chronology and intensity of the renal aggression cannot be specified&#46; The assumption that the biomarkers&#8217; good behavior in renal aggression settings&#44; such as sepsis and surgery with extracorporeal circulation&#44; would be similar in HF has created an a priori far from reality&#46; Lastly&#44; the chronology of HF&#44; especially that of exacerbations in which there is no specific element that helps identify the start of the decompensation&#44; takes away from the temporal framework necessary to interpret the evolutionary changes in the biomarker concentrations&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">In conclusion&#44; renal function offers valuable information for the prognostic stratification of patients with HF&#44; both in the stability phase and during decompensations&#46; The GFR determination through formulas is the best method for its assessment&#46; The CKD-EPI &#40;on the MDRD&#41; is the preferred formula&#44; especially that based on CysC&#44; provided it is available&#46; During HF decompensations&#44; urea concentrations &#40;or BUN as an equivalent&#41; adds valuable information&#46; In contrast&#44; the use of tubular damage biomarkers in the specific context of HF has&#44; to date&#44; a debatable practical utility&#44; and its use should be reserved for the research setting&#46;</p></span></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Funding</span><p id="par0165" class="elsevierStylePara elsevierViewall">The manuscript was part of a funded project &#40;PI12&#47;00694&#41; in the bid for grants to research projects of the Carlos <span class="elsevierStyleSmallCaps">III</span> Health Institute of Spain&#44; Ministry of Economy and Competitiveness&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Conflict of interests</span><p id="par0170" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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          "identificador" => "xres844940"
          "titulo" => "Abstract"
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              "identificador" => "abst0005"
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        1 => array:2 [
          "identificador" => "xpalclavsec839868"
          "titulo" => "Keywords"
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          "identificador" => "xres844941"
          "titulo" => "Resumen"
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              "identificador" => "abst0010"
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        3 => array:2 [
          "identificador" => "xpalclavsec839869"
          "titulo" => "Palabras clave"
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        4 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Cardiorenal syndrome versus cardiorenal interaction"
        ]
        5 => array:2 [
          "identificador" => "sec0010"
          "titulo" => "Prognostic value of renal dysfunction in heart failure"
        ]
        6 => array:3 [
          "identificador" => "sec0015"
          "titulo" => "Prognostic biomarkers in renal function"
          "secciones" => array:3 [
            0 => array:2 [
              "identificador" => "sec0020"
              "titulo" => "Chronic heart failure"
            ]
            1 => array:2 [
              "identificador" => "sec0025"
              "titulo" => "Acute heart failure"
            ]
            2 => array:3 [
              "identificador" => "sec0030"
              "titulo" => "Biomarkers sensitive to tubular damage"
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                0 => array:2 [
                  "identificador" => "sec0035"
                  "titulo" => "Neutrophil gelatinase-associated lipocalin"
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                1 => array:2 [
                  "identificador" => "sec0040"
                  "titulo" => "Kidney injury molecule-1"
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              ]
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        7 => array:2 [
          "identificador" => "sec0045"
          "titulo" => "Funding"
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        8 => array:2 [
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          "titulo" => "Conflict of interests"
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          "titulo" => "References"
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    "pdfFichero" => "main.pdf"
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    "fechaRecibido" => "2016-11-21"
    "fechaAceptado" => "2017-01-14"
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          "clase" => "keyword"
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          "palabras" => array:6 [
            0 => "Heart failure"
            1 => "Renal failure"
            2 => "Creatinine"
            3 => "Cystatin"
            4 => "Urea"
            5 => "Biomarkers"
          ]
        ]
      ]
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        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
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          "palabras" => array:6 [
            0 => "Insuficiencia cardiaca"
            1 => "Insuficiencia renal"
            2 => "Creatinina"
            3 => "Cistatina"
            4 => "Urea"
            5 => "Biomarcadores"
          ]
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    "resumen" => array:2 [
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Renal function is one of the most consistent prognostic determinants in heart failure&#46; The prognostic information it provides is independent of the ejection fraction and functional status&#46; This article reviews the various renal function assessment measures&#44; with special emphasis on the fact that the patient&#39;s clinical situation and response to the heart failure treatment should be considered for the correct interpretation of the results&#46; Finally&#44; we review the literature on the performance of tubular damage biomarkers&#46;</p></span>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Uno de los determinantes pron&#243;sticos m&#225;s consistentes en la insuficiencia cardiaca es la funci&#243;n renal&#46; La informaci&#243;n pron&#243;stica que proporciona es independiente de la fracci&#243;n de eyecci&#243;n y de la situaci&#243;n funcional&#46; En este art&#237;culo se revisan las diferentes medidas de evaluaci&#243;n de la funci&#243;n renal&#44; haciendo especial &#233;nfasis en que para su correcta interpretaci&#243;n debe tenerse en cuenta la situaci&#243;n cl&#237;nica y la respuesta del paciente al tratamiento de la insuficiencia cardiaca&#46; Finalmente se revisa la literatura sobre el rendimiento de los biomarcadores de da&#241;o tubular&#46;</p></span>"
      ]
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        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Please cite this article as&#58; P&#233;rez Calvo JI&#44; Josa Laorden C&#44; Gim&#233;nez L&#243;pez I&#46; Evaluaci&#243;n de la funci&#243;n renal en la insuficiencia cardiaca&#46; Rev Clin Esp&#46; 2017&#59;217&#58;267&#8211;288&#46;</p>"
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Temporal evolution of biomarker concentrations after a renal aggression&#46; <span class="elsevierStyleItalic">Source</span>&#58; modified from Malyszko et al&#46;<a class="elsevierStyleCrossRef" href="#bib0695"><span class="elsevierStyleSup">11</span></a><span class="elsevierStyleItalic">Abbreviations</span>&#58; IL-18&#44; interleukin 18&#59; KIM-1&#44; kidney injury molecule type 1&#59; L-FABP&#44; liver-type fatty-acid binding protein&#59; NGAL&#44; neutrophil gelatinase-associated lipocalin&#46;</p>"
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          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Relationship between the biomarkers and the function or structure of the analyzed nephron&#46; <span class="elsevierStyleItalic">Source</span>&#58; modified from Malyszko et al&#46;<a class="elsevierStyleCrossRef" href="#bib0695"><span class="elsevierStyleSup">11</span></a><span class="elsevierStyleItalic">Abbreviations</span>&#58; Alpha-GST&#44; alpha-glutathione S-transferase&#59; IL-18&#44; interleukin 18&#59; KIM-1&#44; kidney injury molecule type 1&#59; L-FABP&#44; Liver-type fatty-acid binding protein&#59; NGAL&#44; neutrophil gelatinase-associated lipocalin&#46;</p>"
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          "leyenda" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Source</span>&#58; Damman and Testani<a class="elsevierStyleCrossRef" href="#bib0645"><span class="elsevierStyleSup">1</span></a> and Damman et al&#46;<a class="elsevierStyleCrossRef" href="#bib0690"><span class="elsevierStyleSup">10</span></a></p><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Abbreviations</span>&#58; GFR&#44; glomerular filtration rate&#59; G&#44; grade&#46;</p>"
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                  <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="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Category by GFR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">GFR &#40;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</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Definition&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">G1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8805;90&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Normal renal function&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">G2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">60&#8211;89&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Mild decrease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">G3a<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">45&#8211;59&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Mild to moderate decrease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">G3b<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">30&#8211;44&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Moderate to intense decrease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">G4<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">15&#8211;29&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Intense decrease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">G5<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Renal impairment&nbsp;\t\t\t\t\t\t\n
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              "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Category 3a onwards is considered renal failure&#46;</p>"
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          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Categories of chronic kidney disease based on glomerular filtration rate<a class="elsevierStyleCrossRefs" href="#bib0645"><span class="elsevierStyleSup">1&#44;10</span></a></p>"
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          "leyenda" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Abbreviations</span>&#58; BDI&#44; Beck depression inventory&#59; BNP&#44; brain natriuretic peptide&#59; RFI&#44; renal function impairment&#59; EPO&#44; erythropoietin&#59; LVEF&#44; left ventricular ejection fraction&#59; GFR&#44; glomerular filtration rate&#59; eGFR&#44; estimated glomerular filtration rate&#59; HAMD&#44; Hamilton depression rating scale&#59; HR&#44; hazard ratio&#59; PHT&#44; pulmonary hypertension&#59; HF&#44; heart failure&#59; AHF&#44; acute heart failure&#59; CHF&#44; chronic heart failure&#59; IL-18&#44; interleukin-18&#59; CRF&#44; chronic renal failure&#59; MACE&#44; major adverse cardiovascular events&#59; CM&#44; cardiomyopathy&#59; NT-proBNP&#44; amino-terminal fragment of the brain natriuretic peptide&#59; OR&#44; odds ratio&#59; pKIM-1&#44; plasma kidney injury molecule-1&#59; pNGAL&#44; plasma neutrophil gelatinase-associated lipocalin&#59; ROC&#44; receiver operating characteristics&#59; ST-2&#44; suppression of tumorigenesis 2&#59; CCU&#44; cardiac care unit&#59; uKIM-1&#44; urinary kidney injury molecule-1&#59; uNAG&#44; urinary N-acteyl-&#946;-<span class="elsevierStyleSmallCaps">d</span>-glucosaminidase&#59; uNGAL&#44; urinary neutrophil gelatinase-associated lipocalin&#59; LV&#44; left ventricle&#46;</p>"
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                  <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="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Reference &#40;first author&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Year&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">n</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Type of HF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Objectives&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Biomarkers&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Results&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Conclusions&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Correlation with objectives&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Jungbauer<a class="elsevierStyleCrossRef" href="#bib1090"><span class="elsevierStyleSup">90</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2015&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">138&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">CHF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">ANALYTICAL&#46; Value of new urinary markers for predicting progression to CRF &#40;5-year follow-up&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">uNGAL uKIM-1 uNAG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Progression to CRF&#58; 18&#46;8&#37;<br>Cox Regression&#58; NAG<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>median &#40;OR&#44; 3&#46;81&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;005&#41;&#44; initial GFR &#40;OR&#44; 0&#46;94&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; and the use of diuretics &#40;OR&#44; 3&#46;25&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;002&#41; were independent predictors of CRF&#46; KIM-1 and NAG were independent predictors of the combined variable progression to CRF and all-cause mortality&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Strong association between the tubular markers NAG and KIM-1 and progression to CRF in CHF&#44; which indicates their usefulness in combination as cardiorenal markers&#46; NGAL showed no association with progression to CRF&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Positive&#47;negative for NGAL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Emmens<a class="elsevierStyleCrossRef" href="#bib1095"><span class="elsevierStyleSup">91</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2015&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2153&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">120 CHF 2033 AHF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">CLINICAL&#46; Relationship between KIM-1 in plasma and heart failure&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">pKIM-1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">CHF&#58; pKIM-1 was associated with eGFR&#44; creatinine&#44; cystatin and urinary NAG but not with other markers of urinary tubular damage&#46; Log pKIM-1 predicted adverse events&#44; but this association was lost after the correction by NT-proBNP &#40;HR&#44; 1&#46;61&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;175&#41;&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">pKIM-1 is associated with the GFR and urinary NAG&#46; pKIM-1 did not predict events in CHF after correction by NT-proBNP&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ventoulis<a class="elsevierStyleCrossRef" href="#bib1100"><span class="elsevierStyleSup">92</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2015&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">76&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">CHF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">CLINICAL&#46; Relationship between pNGAL and sST2 with clinical characteristics and cardiac function in CHF&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">pNGAL pST2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">There was no association between pNGAL and pST2&#46; The multivariate analysis revealed that the right ventricular systolic velocity in the tissue Doppler was an independent predictor of sST2&#44; and the duration of the heart failure&#44; and the serum creatinine values were independent predictors of NGAL&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">The NGAL values depend on renal function and HF progression time&#44; while ST2 is affected by the right ventricular function and showed no association with the clinical indices of HF&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Villacorta<a class="elsevierStyleCrossRef" href="#bib1105"><span class="elsevierStyleSup">93</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2015&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">61&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">CHF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">PROGNOSTIC&#46; pNGAL value for predicting cardiovascular events in patients with stable heart failure&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">pNGAL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">The patients with events had poorer renal function and higher NGAL values &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;006&#41;&#46; NGAL correlated with creatinine &#40;<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;50&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;0001&#41;&#44; albuminuria &#40;<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;33&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;008&#41; and eGFR &#40;<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#8722;0&#46;47&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;0001&#41; but not with BNP &#40;<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;003&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;97&#41;&#46;<br>ROC curve&#58; patients with NGAL &#62;179<span class="elsevierStyleHsp" style=""></span>ng&#47;mL had lower survival&#46; NGAL was independently related to adverse events &#40;HR&#44; 1&#46;0035&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;0001&#41;&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NGAL correlates with other renal function markers but not with BNP&#44; and is associated with cardiovascular events&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Pronschinske<a class="elsevierStyleCrossRef" href="#bib1110"><span class="elsevierStyleSup">94</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2014&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">144&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">40 CHF 40 ventricular assistance 40 ventricular assistance withdrawn in heart transplant 24 controls&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">PROGNOSTIC&#46; Prognostic role of pNGAL and cystatin C compared with other established markers of renal dysfunction&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">pNGAL Cystatin C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Patients with CHF had higher levels of pNGAL and cystatin C&#46; Higher pNGAL levels were associated with advanced HF with implantation of ventricular assistance devices&#44; right ventricular failure and irreversible renal dysfunction&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">pNGAL levels were correlated with CHF severity and with hemodynamic improvement after the implantation of the ventricular assistance device&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Damman<a class="elsevierStyleCrossRef" href="#bib1115"><span class="elsevierStyleSup">95</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2013&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2011&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">CHF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">ANALYTICAL&#46; Relationship between tubular damage and renal function impairment&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">uNAG uKIM-1 uNGAL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Renal function impairment was an independent predictor of overall mortality and readmissions for heart failure &#40;HR&#44; 2&#46;87&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46;<br>Patients with renal function impairment had higher urine values of KIM-1&#44; NG and NGAL&#46; KIM-1 was the strongest independent predictor of renal function impairment &#40;HR&#44; 1&#46;23&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">The increase in uKIM-1 was the strongest predictor of renal function impairment&#44; identifying patients with greatest risk of renal impairment and poorer prognosis&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Naud&#233;<a class="elsevierStyleCrossRef" href="#bib1120"><span class="elsevierStyleSup">96</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2014&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">104&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">CHF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">CLINICAL&#46; Association between pNGAL and depressive symptoms in CHF&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">pNGAL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">High pNGAL levels were related to depression measured with the HAMD scale &#40;baseline&#58; <span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;25&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41; and BDI &#40;baseline&#58; <span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;22&#44; &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#59; at 12 months&#58; <span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;37&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#41; pNGAL was associated with somatic symptoms &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;004&#41; but not with depressive symptoms at the cognitive level &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;32&#41;&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Depression in patients with CHF is associated with higher pNGAL levels&#44; regardless of the clinical severity of the underlying disease&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Van Deursen<a class="elsevierStyleCrossRef" href="#bib1085"><span class="elsevierStyleSup">89</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2014&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">562&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">CHF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">PROGNOSTIC&#46; Association between pNGAL and prognosis &#40;overall mortality at 36 months&#41;&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">pNGAL Cystatin C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">High pNGAL levels are associated with a greater risk of overall mortality&#44; in patients with or without CKD &#40;HR&#44; 1&#46;45&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001 and HR&#44; 1&#46;51&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;023&#41;&#46; When NGAL is part of the multivariate model&#44; eGFR and cystatin C are not associated with mortality&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">pNGAL predicts mortality in patients with heart failure regardless of the chronic renal failure and is a stronger prognostic factor than eGFR and cystatin C&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Driver<a class="elsevierStyleCrossRef" href="#bib1125"><span class="elsevierStyleSup">97</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2014&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2917&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Healthy controls<span class="elsevierStyleHsp" style=""></span>&#8594;<span class="elsevierStyleHsp" style=""></span>risk of developing HF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">CLINICAL&#46; Association between urinary biomarkers of renal tubular damage and the risk of developing heart failure&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">uIL-18 uKIM-1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Development of HF&#58; 20&#46;4&#37;&#46; KIM-1&#58; After multivariate adjustment&#44; KIM-1 is associated with a greater incidence of heart failure &#40;HR&#44; 1&#46;32&#41;&#46; IL-18&#58; Not associated after the adjustment &#40;HR&#44; 1&#46;15&#59; 95&#37; CI 0&#46;89&#8211;1&#46;48&#41;&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Higher KIM-1 concentrations are independently related to a greater risk of developing heart failure&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Carlsson<a class="elsevierStyleCrossRef" href="#bib1080"><span class="elsevierStyleSup">88</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2013&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">565&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Healthy controls<span class="elsevierStyleHsp" style=""></span>&#8594;<span class="elsevierStyleHsp" style=""></span>risk of developing HF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">CLINICAL&#46; Assess whether KIM-1&#44; as a specific marker of renal tubular damage&#44; predisposes the patient to a high risk of HF&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">uKIM-1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">12&#46;9&#37; hospitalizations for HF&#46; In the adjusted model&#44; a high KIM-1&#47;creatinine ratio was associated with a greater risk of HF &#40;HR&#44; 1&#46;81&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46;<br>The combination of a GFR &#60;60<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#47;1&#46;72<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span> and KIM-1&#47;creatinine &#62;128<span class="elsevierStyleHsp" style=""></span>ng&#47;mmol represents a 3-fold greater risk of developing HF than normal &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Renal tubular damage predisposes patients to an increased risk of developing HF in the community&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Emans<a class="elsevierStyleCrossRef" href="#bib1130"><span class="elsevierStyleSup">98</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2012&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">56&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">CHF with CRF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">ANALYTICAL&#46; Correlation between pNGAL and iron metabolism and whether treatment with erythropoietin modulates pNGAL&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">pNGAL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NGAL is not correlated with hepcidin or transferrin saturation&#46; pNGAL correlates with erythropoietin levels &#40;<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#8722;0&#46;395&#41; and decreases after 2 weeks of treatment with erythropoietin &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;02&#41;&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">In the combination CHF<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>CRF&#44; pNGAL is not correlated with iron metabolism but is inversely correlated with baseline EPO levels&#44; which decrease in the short term after treatment with erythropoietin stimulants&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Shrestha<a class="elsevierStyleCrossRef" href="#bib1135"><span class="elsevierStyleSup">99</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2012&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">130&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">CHF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">ANALYTICAL&#46; Relationship between pNGAL and anemia &#40;regardless of renal function&#41;&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">pNGAL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">pNGAL is inversely correlated with anemia &#40;<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#8722;0&#46;38&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;0001&#41;&#46; Higher pNGAL levels are associated with anemia regardless of the GFR&#44; C-reactive protein levels and myeloperoxidase levels &#40;OR 2&#46;38&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;045&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">pNGAL levels are independently associated with anemia indices&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Nymo<a class="elsevierStyleCrossRef" href="#bib1140"><span class="elsevierStyleSup">100</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2012&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1415&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">CHF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">PROGNOSTIC&#46; Study of the prognostic value of pNGAL in CHF of ischemic etiology&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">pNGAL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Multivariate study&#58; pNGAL added prognostic information after adjustment for clinical variables but was not significant when adjusted for apolipoprotein A-1&#44; GFR&#44; C-reactive protein and NT-proBNP&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">pNGAL did not add prognostic information to NT-proBNP and eGFR in patients with ischemia&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Koca<a class="elsevierStyleCrossRef" href="#bib1145"><span class="elsevierStyleSup">101</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2011&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">90&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">35 nonischemic CM 28 PHT 27 controls&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">ANALYTICAL&#46; Significance of NGAL in right-sided heart failure&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">pNGAL uNGAL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">pNGAL and uNGAL levels were no different between the 2 groups &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;15 and <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;35&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Neither pNGAL nor uNGAL levels were high in this patient cohort&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Damman<a class="elsevierStyleCrossRef" href="#bib1150"><span class="elsevierStyleSup">102</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2011&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2131&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">CHF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">PROGNOSTIC&#46; Relationship between tubular damage&#44; GFR&#44; urinary excretion of albumin and prognosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">uNGAL uKIM-1 uNAG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">All tubular markers were independently associated with the combined event&#58; NAG&#58; HR 1&#46;22&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#44; KIM-1 HR 1&#46;13&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;018 and NGAL HR 1&#46;10&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;042&#59; including in those with normal GFR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Tubular damage is related to a poorer prognosis even if the GFR is normal&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Shrestha<a class="elsevierStyleCrossRef" href="#bib1155"><span class="elsevierStyleSup">103</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2011&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">199&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">130 CHF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">PROGNOSTIC and CLINICAL&#46; Relationship between pNGAL and the cardiac structure and prognosis&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">pNGAL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NGAL was modestly related to impaired renal function &#40;eGFR&#58; <span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;53&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;0001&#59; cystatin C&#58; <span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;60&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;0001&#41; and with diastolic dysfunction but not after adjusting for renal function&#46; pNGAL predicted cardiac death or transplantation after adjusting for age&#44; sex&#44; LVEF and mitral E&#47;Ea but not after adjusting for renal function &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;83&#41;&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">There is no prognostic relationship between pNGAL and the indices of cardiac structure after adjusting for prior renal function&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Jungbauer<a class="elsevierStyleCrossRef" href="#bib1160"><span class="elsevierStyleSup">104</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2011&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">173&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">CHF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">ANALYTICAL&#46; Analyze whether the new urinary markers of kidney damage are high in CHF and cardiorenal syndrome&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">uNGAL uKIM-1 uNAG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">uKIM-1 was high in patients with HF&#44; increasing with the reduction of LV function &#40;<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#8722;0&#46;37&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; and with the severity of the NYHA functional class &#40;<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;5&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; uNGAL showed no correlation&#46; uKIM-1 and NAG were predictors of overall mortality and readmissions for heart failure&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">uKIM-1 and uNAG were high in patients with symptomatic HF&#44; in patients with normal renal function&#44; which indicates tubular damage&#46; uKIM-1 and NAG are potential markers of cardiorenal syndrome with additional prognostic meaning&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Damman<a class="elsevierStyleCrossRef" href="#bib0710"><span class="elsevierStyleSup">14</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2011&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">30&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">CHF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">ANALYTICAL&#46; Effect of the modulation of diuretic treatment on renal markers&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">uNGAL pNGAL uKIM-1 uNAG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">uKIM-1 &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; and uNAG &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#41; levels increased significantly after the diuretics were withdrawn&#46; After restarting furosemide&#44; both markers returned to their baseline levels &#40;both <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#44; while NGAL was not affected at any of the 2<span class="elsevierStyleHsp" style=""></span>moments&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Subclinical changes in the blood volume condition are associated with changes in tubular function markers in CHF&#46; Diuretic therapy can favorably affect renal and tubular function by decreasing congestion&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Positive&#47;negative for NGAL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Damman<a class="elsevierStyleCrossRef" href="#bib1165"><span class="elsevierStyleSup">105</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2010&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">90&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">CHF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">ANALYTICAL and PROGNOSTIC&#46; Investigate the prevalence of tubular damage&#44; its association with GFR and prognosis&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">uNGAL uKIM-1 uNAG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">The levels of uNGAL&#44; uNAG and uKIM-1 were increased compared with the controls &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; uNGAL was correlated with GFR &#40;<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#8722;0&#46;34&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; but not with the other markers&#46; Both uKIM-1 &#40;HR 1&#46;15&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;025&#41; and uNAG &#40;HR 1&#46;42&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;039&#41; were associated with an increased risk of death or readmissions for HF&#44; regardless of GFR&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Tubular damage is common in patients with CHF and moderately reduced GFR&#46; uKIM-1 and uNAG provided additional prognostic information to GFR&#46; These findings indicate the important role of tubular damage and tubular markers in the cardiorenal interaction in HF&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Poniatowski<a class="elsevierStyleCrossRef" href="#bib1170"><span class="elsevierStyleSup">106</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2009&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">150&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">CHF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">ANALYTICAL&#46; NGAL as a marker of renal function in CHF and normal serum creatinine&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">pNGAL uNGAL Cystatin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">In the multiple regression study&#44; the predictors of pNGAL were the NYHA functional state&#44; cystatin C and eGFR&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NGAL should be investigated as a powerful&#44; sensitive and early marker of kidney damage&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Bolignano<a class="elsevierStyleCrossRef" href="#bib1175"><span class="elsevierStyleSup">107</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2009&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">46&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">CHF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NGAL as a predictor of mortality in elderly patients&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">pNGAL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">The pNGAL levels were higher in patients with HF compared with controls &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;0001&#41; and increased in parallel with the functional severity &#40;NYHA&#41; &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;0001&#41;&#46;<br>Patients with baseline pNGAL<span class="elsevierStyleHsp" style=""></span>&#62;783<span class="elsevierStyleHsp" style=""></span>ng&#47;mL &#40;best cutoff on the ROC curve&#41; showed a 4-fold greater mortality at 2<span class="elsevierStyleHsp" style=""></span>years of follow-up &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">For the first time&#44; the measurement of pNGAL was indicated as having prognostic value for patients with CHF&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Damman<a class="elsevierStyleCrossRef" href="#bib1180"><span class="elsevierStyleSup">108</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2008&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">110&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">90 CHF&#44; 20 healthy controls&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">uNGAL as a new marker of tubular damage&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">uNGAL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">The mean uNGAL values were increased compared with controls &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;0001&#41;&#46; Creatinine &#40;<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;26&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;006&#41; and eGFR &#40;<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#8722;0&#46;29&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;002&#41; were associated with uNGAL levels&#44; as with NT-proBNP and the urinary excretion of albumin&#44; although to a lesser degree&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Renal impairment in CHF is not only characterized by the urinary excretion of albumin and a reduced eGFR but also by the presence of tubular damage&#44; as measured by the concentration of uNGAL&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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                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="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Reference&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Year&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">N</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Type of HF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Objectives&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Biomarkers&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Results&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Conclusions&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Correlation with objectives&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Helanova<a class="elsevierStyleCrossRef" href="#bib1185"><span class="elsevierStyleSup">109</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2015&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">673&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">AHF with STE-ACS after primary angioplasty&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">PROGNOSTIC&#46; Usefulness of NGAL for the prognostic stratification added to the TIMI score and compared with the BNP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">pNGAL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">The AUC as predictors of mortality for NGAL&#44; BNP and TIMI were 75&#46;5&#59; 78&#46;7 and 74&#46;4&#44; respectively &#40;all <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; For the presence of a combined event&#44; the values were 80&#46;6 for BNP and 82&#46;2 for TIMI and NGAL&#46; NGALv&#62;<span class="elsevierStyleHsp" style=""></span>110<span class="elsevierStyleHsp" style=""></span>pg&#47;mL was associated with a 1-year mortality of 20&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">The combination of NGAL and TIMI score was strong &#40;in a prognostic model&#41; for the probability of mortality at 1 year in patients with STE-ACS&#46; NGAL by itself is a useful tool for identifying high-risk patients&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Emmens<a class="elsevierStyleCrossRef" href="#bib1095"><span class="elsevierStyleSup">91</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2015&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2153&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">120 CHF 2033 AHF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">CLINICAL&#46; Relationship between the KIM-1 marker in plasma and HF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">pKIM-1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">AHF&#58; higher plasma KIM-1 values were associated with higher creatinine and lower albumin values and diabetes&#46; pKIM-1 predicted rehospitalization for HF at 60 days &#40;HR 1&#46;27&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;024&#41; but not mortality at 180 days or death at 60 days&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">pKIM-1 is associated with GFR and urinary NAG&#46; pKIM-1 predicted readmissions for AHF&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Grodin<a class="elsevierStyleCrossRef" href="#bib1190"><span class="elsevierStyleSup">110</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2015&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">874&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">AHF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">PROGNOSTIC&#46; Relationship between pKIM-1 and adverse events&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">pKIM-1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">There is no relationship between KIM-1 and events at 30 days&#46;<br>After a multivariate fit for urea and creatinine&#44; higher KIM-1 levels were not associated with intrahospital events or after discharge&#46; However&#44; KIM-1 levels measured at 30 days &#40;stable phase&#41; were independently related with mortality at 180 days &#40;HR&#44; 1&#46;49&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;04&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">KIM-1 levels at baseline and during hospitalization were not associated with adverse events in AHF after adjusting for renal function&#46;<br>The values in stable phase did have a prognostic value at 180 days&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ito<a class="elsevierStyleCrossRef" href="#bib1195"><span class="elsevierStyleSup">111</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2015&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">101&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">AHF &#40;discharged from the CCU&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">PROGNOSTIC&#46; NGAL as a predictor of mortality and MACE after discharge from the CCU&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">pNGAL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">pNGAL&#44; hospital stay in the CCU&#44; diabetes and HF were independent predictors of MACE in the multivariate analysis&#46; Patients with NGAL at discharge<span class="elsevierStyleHsp" style=""></span>&#62;75th percentile showed a greater risk of MACE &#40;log-rank test&#59; HR&#44; 5&#46;15&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">The measurement of plasma NGAL at discharge from the CCU is a prognostic indicator of adverse events at 6 months in critically ill patients&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Palazzuoli<a class="elsevierStyleCrossRef" href="#bib1200"><span class="elsevierStyleSup">112</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2015&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">231&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">AHF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">ANALYTICAL and PROGNOSTIC&#46; Role of NGAL in predicting ARD and events&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">pNGAL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">34&#37; ARD&#46; An NGAL<span class="elsevierStyleHsp" style=""></span>&#62;134<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&#44; with a 85&#37; sensitivity and 80&#37; specificity &#40;AUC 0&#46;81&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; was associated with the development of ARD&#46; The increase in NGAL<span class="elsevierStyleHsp" style=""></span>&#62;170<span class="elsevierStyleHsp" style=""></span>ng&#47;mL was associated with high mortality &#40;cutoff of 170<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&#44; 60&#37; sensitivity&#44; 82&#37; specificity&#44; AUC 0&#46;77&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NGAL is a sensitive tool for predicting ARD during AHF&#46; NGAL is related to increases in urea levels and adverse events after discharge&#46; This indicated the prognostic role of tubular damage added to that of renal dysfunction&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Kirbis<a class="elsevierStyleCrossRef" href="#bib1205"><span class="elsevierStyleSup">113</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2015&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">62&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">AHF with STE-ACS after primary angioplasty&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">CLINICAL&#46; Correlates uNGAL with AHF in patients with STE-ACS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">uNGAL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">uNGAL levels are higher in patients with AHF&#46; The cutoff of 50<span class="elsevierStyleHsp" style=""></span>ng&#47;mL showed a 90&#37; specificity for AHF but with a low sensitivity of 25&#37;&#46; When comparing patients with uNGAL levels<span class="elsevierStyleHsp" style=""></span>&#60; and those with uNGAL levels &#62;50<span class="elsevierStyleHsp" style=""></span>ng&#47;dL&#44; both at admission and 12<span class="elsevierStyleHsp" style=""></span>h later&#44; differences were observed in levels of NT-proBNP&#44; LVEF&#44; inflammation markers and renal function markers&#46; uNGAL was independently associated with NT-proBNP&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">The early measurement of NGAL levels after an STE-ACS is associated with NT-proBNP levels&#44; and even levels lower than normal &#40;137<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&#41;&#44; have a high specificity for the development of AHF&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Soyler<a class="elsevierStyleCrossRef" href="#bib1210"><span class="elsevierStyleSup">114</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2015&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">AHF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">ANALYTICAL and CLINICAL&#46; Usefulness of uNGAL for predicting diuretic treatment requirements and the development of ARD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">uNGAL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Those patients who developed ARD had higher uNGAL levels &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; and had a lower oral diuretic dosage at admission &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;023&#41;&#46; ROC curve&#58; An uNGAL level of 12<span class="elsevierStyleHsp" style=""></span>ng&#47;mL presented a 79&#37; sensitivity and 67&#37; specificity for predicting ARD&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">uNGAL levels in AHF are an appropriate urinary marker for predicting ARD&#44; with a cutoff of 12<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Deerardinis<a class="elsevierStyleCrossRef" href="#bib1215"><span class="elsevierStyleSup">115</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2015&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">101&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">AHF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">PROGNOSTIC&#46; Capacity of biomarkers for predicting the occurrence of WRF and hospital death&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NT-proBNP BNP pST2 pNGAL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">26&#37; patients developed WRF&#46; For the development of WRF&#58; NT-proBNP<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>NGAL &#40;OR 2&#46;79&#41; and for BNP<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>NGAL &#40;OR 3&#46;11&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">In the emergency department&#44; the combination of NT-proBNP or BNP plus NGAL at admission is useful for predicting the development of renal function impairment in patients with AHF&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Tung<span class="elsevierStyleSup">116</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2015&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">189&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">AHF&#46; STE-ACS after primary angioplasty&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">ANALYTICAL&#46; Usefulness of biomarkers for predicting the development of ARD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">pNGAL pST2 pCystatin<br>BNP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">19&#46;6&#37; of ARD&#46; The 4 ARD markers with discriminative capacity&#58; AUC ROC&#58; BNP&#58; 0&#46;86&#59; pST2&#58; 0&#46;74&#59; pNGAL&#58; 0&#46;75&#59; cystatin C&#58; 0&#46;73 &#40;all <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46; The increase of &#8805;2 biomarkers above the levels derived from the ROC curves improved the risk stratification of ARD&#44; regardless of creatinine levels &#40;creatinine<span class="elsevierStyleHsp" style=""></span>&#60;1&#46;24<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#58; OR&#44; 11&#46;25&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;014&#59; creatinine &#8805;1&#46;24&#58; OR&#44; 15&#46;0&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;034&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">The biomarkers of HF &#40;BNP and spST2&#41; and renal damage &#40;NGAL and cystatin C&#41; at admission were predictors of ARD&#46; The combination of biomarkers &#40;&#8805;2&#41; can help make a better risk stratification of ARD in patients with STE-ACS&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Torregrosa<a class="elsevierStyleCrossRef" href="#bib1225"><span class="elsevierStyleSup">117</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2015&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">193&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">ACS&#47;AHF with angiography coronary&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">ANALYTICAL&#46; Markers for the early detection of ARD after coronary angiography&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">KIM-1 NGAL L-FABP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">ROC&#58; AUC for KIM-1 &#40;0&#46;713&#41;&#44; NGAL &#40;0&#46;958&#41; and L-FABP &#40;0&#46;642&#41;&#46; uAKI 12<span class="elsevierStyleHsp" style=""></span>h after the angiography was a predictor of ARD&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">KIM-1 showed the best sensitivity and specificity for the development of ARD after coronary angiography&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Palazzuoli<a class="elsevierStyleCrossRef" href="#bib1230"><span class="elsevierStyleSup">118</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2014&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">AHF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">PROGNOSTIC and ANALYTICAL&#46; The role of NGAL in predicting renal function impairment and prognosis at 6 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">pNGAL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">pNGAL levels were high in patients with chronic renal failure and in ARD&#46;<br>pNGAL levels<span class="elsevierStyleHsp" style=""></span>&#62;134<span class="elsevierStyleHsp" style=""></span>pg&#47;mL were related to the worsening of renal function &#40;92&#37; sensitivity&#44; 71&#37; specificity&#44; AUC 0&#46;83&#41;&#46; Cox regression&#58; pNGAL HR 1&#46;75 <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001 for mortality at 6 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">The measurement of pNGAL at admission is a sensitive tool for predicting renal function impairment and as a marker of adverse prognosis after discharge&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Verbrugge<a class="elsevierStyleCrossRef" href="#bib1235"><span class="elsevierStyleSup">119</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2013&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">83&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">AHF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">PROGNOSTIC and CLINICAL&#46; Predictive value of uNGAL&#44; uKIM-1 and uIL-18 for ARD&#44; persistent renal impairment and mortality&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">uNGAL uKIM-1 uIL-18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No marker predicted ARD during AHF&#46; uIL-18&#47;creatinine was the strongest predictor of a persistent increase in serum creatinine &#8805;0&#46;3<span class="elsevierStyleHsp" style=""></span>mg&#47;dL 6 months after hospitalization&#44; compared with baseline levels &#40;AUC&#44; 0&#46;674&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;013&#41;&#46; uIL-18 was associated with overall mortality &#40;HR&#44; 1&#46;48&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">uNGAL&#44; KIM-1 and uIL-18 are modest predictors of ARD&#46; More studies are needed to support the prognostic value of uIL-18&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Mortara<a class="elsevierStyleCrossRef" href="#bib1240"><span class="elsevierStyleSup">120</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2013&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">30&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">AHF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">ANALYTICAL&#46; pNGAL as an early predictor of renal function impairment during episodes of AHF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">pNGAL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Prevalence of renal function impairment 26&#46;7&#37;&#46;<br>pNGAL at admission is related to eGFR and creatinine levels but did not predict the development of renal function impairment&#46; If NGAL levels rise during the hospital stay&#44; they predict renal impairment&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Serial pNGAL measures during the first days of hospitalization can accurately predict renal function impairment&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Park<a class="elsevierStyleCrossRef" href="#bib1245"><span class="elsevierStyleSup">121</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2013&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">53&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">AHF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">ANALYTICAL&#46; Correlation between uNGAL and uKIM-1 and renal recovery ARD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">uNGAL uKIM-1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">The mean NGAL and KIM-1 levels were similar in patients with and without ARD and were not associated with creatinine recovery&#46; KIM-1 levels increased during the first 5 days of hospitalization in patients without ARD&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">uKIM-1 and uNGAL were not related to creatinine recovery after an episode of ARD&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Shrestha<a class="elsevierStyleCrossRef" href="#bib1155"><span class="elsevierStyleSup">103</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2012&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">93&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">AHF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">ANALYTICAL&#46; Correlation between NGAL in plasma and urine and renal function&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">pNGAL uNGAL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">pNGAL and uNGAL are modestly correlated &#40;<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;37&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;0001&#41;&#46; High uNGAL levels correlate with markers of natriuresis and reduced diuresis&#46; Both markers predict ARD &#40;uNGAL&#59; OR&#44; 1&#46;7&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;035&#59; pNGAL&#59; OR&#44; 1&#46;9&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;009&#41;&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">pNGAL and uNGAL are predictors of renal function impairment&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Collins<a class="elsevierStyleCrossRef" href="#bib1255"><span class="elsevierStyleSup">123</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2012&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">399&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">AHF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">PROGNOSTIC&#46; Relationship between uNGAL at admission and changes during hospitalization on one hand and worsening renal function and adverse events on the other &#40;at 5 and 30 days&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">uNGAL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">uNGAL levels at 12&#8211;24<span class="elsevierStyleHsp" style=""></span>h were still a significant predictor of renal function impairment &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;012&#41;&#46; uNGAL was the only predictor of adverse events at 30 days &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;02&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">uNGAL levels measured 12&#8211;24<span class="elsevierStyleHsp" style=""></span>h after treatment were associated with worsening renal function at 72&#8211;96<span class="elsevierStyleHsp" style=""></span>h and adverse events at 30 days&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Dupont<a class="elsevierStyleCrossRef" href="#bib1260"><span class="elsevierStyleSup">124</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2012&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">141&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">AHF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">ANALYTICAL&#46; Determine whether ARD in AHF is accompanied by tubular damage measured by uNGAL&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">uNGAL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">The median uNGAL&#47;uCreat on day 1 of hospitalization was similar in patients who developed ARD or not&#46; The differences were significant only on day 3 &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;02&#41;&#46; There was no difference in the response to diuretics between the patients with uNGAL&#47;uCreat&#43; &#40;&#62;27<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;g&#41; and those with uNGAL&#47;uCreat- &#40;&#60;27<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;g&#41;&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">There was no evidence of renal tubular damage despite the ARD in patients with AHF&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">MacDonald<a class="elsevierStyleCrossRef" href="#bib1265"><span class="elsevierStyleSup">125</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2012&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">102&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">AHF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">PROGNOSTIC and ANALYTICAL&#46; Assess whether pNGAL measured at admission predicts the development of intrahospital ARD&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">pNGAL BNP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">ARD 25&#37; pNGAL was associated with the development of ARD &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;002&#41; and mortality &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;005&#41;&#46; NGAL levels<span class="elsevierStyleHsp" style=""></span>&#62;89<span class="elsevierStyleHsp" style=""></span>ng&#47;mL predicted ARD with 68&#37; sensitivity and 70&#37; specificity&#59; AUC&#44; 0&#46;71&#59; kidney damage OR&#58; 3&#46;73 if pNGAL levels at admission were &#62;89<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">High pNGAL levels at admission were associated with the development of ARD and mortality during hospitalization for AHF&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Alvelos<a class="elsevierStyleCrossRef" href="#bib1270"><span class="elsevierStyleSup">126</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2013&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">121&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">AHF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">PROGNOSTIC&#46; Prognostic role of pNGAL and cystatin C at 3 months &#40;mortality and combined with readmissions for HF&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">pNGAL Cystatin C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">The variables associated with increased mortality in the univariate study were advanced age and high levels of BNP&#44; cystatin C and pNGAL&#46;<br>BNP and pNGAL remained as independent predictors of mortality and combined event&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">pNGAL is an independent predictor of poorer short-term prognosis in patients with AHF&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Maisel<a class="elsevierStyleCrossRef" href="#bib1275"><span class="elsevierStyleSup">127</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2011&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">186&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">AHF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">PROGNOSTIC&#46; Prognostic utility of pNGAL as an early marker of adverse events at 30 days&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">pNGAL BNP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Multivariate study&#58; pNGAL predicted events &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; Adding the measurement of pNGAL at discharge improved the net prognostic reclassification by 29&#46;8&#37; &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#41;&#44; compared with BNP alone&#46; Patients with high BNP and pNGAL levels had a greater risk of adverse events &#40;HR&#44; 16&#46;85&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;006&#41;&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">pNGAL is a measure of kidney damage and is considered a powerful prognostic indicator at 30 days&#44; better than BNP alone&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Shrestha<a class="elsevierStyleCrossRef" href="#bib1155"><span class="elsevierStyleSup">103</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2011&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">199&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">69 AHF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">PROGNOSTIC and CLINICAL&#46; Relationship between pNGAL and the cardiac structure and prognosis&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">pNGAL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">There was no relationship between pNGAL and hemodynamic indices&#44; but pNGAL was strongly correlated with renal function&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">There is no prognostic relationship between pNGAL and the indices of cardiac structure after adjusting for prior renal function&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Aghel<a class="elsevierStyleCrossRef" href="#bib1280"><span class="elsevierStyleSup">128</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2010&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">91&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">AHF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">ANALYTICAL&#46; Relationship between pNGAL levels at admission and the incidence of renal function impairment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">pNGAL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Renal function impairment&#58; 38&#37; at 5 days of follow-up&#46; The patients who developed renal function impairment had higher pNGAL levels at admission &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46;<br>pNGAL values &#8805;140<span class="elsevierStyleHsp" style=""></span>ng&#47;mL at admission represented a 7&#46;4-fold greater risk of developing renal function impairment during the hospitalization&#44; with 86&#37; sensitivity and 54&#37; specificity&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">The presence at admission of high pNGAL concentrations was associated with an 8-fold greater risk of developing renal function impairment in patients hospitalized for AHF&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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          "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Results of the studies with tubular damage biomarkers in chronic or stable &#40;A&#41; and acute &#40;B&#41; heart failure&#46;<a class="elsevierStyleCrossRefs" href="#bib1090"><span class="elsevierStyleSup">90&#8211;128</span></a></p>"
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Review
Renal function assessment in heart failure
Evaluación de la función renal en la insuficiencia cardiaca
J.I. Pérez Calvoa,b,c,
Corresponding author
jiperez@unizar.es

Corresponding author.
, C. Josa Laordena,b,c, I. Giménez Lópezb,c
a Servicio de Medicina Interna, Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain
b Instituto de Investigación Sanitaria de Aragón (IIS Aragón), Zaragoza, Spain
c Facultad de Medicina, Universidad de Zaragoza, Zaragoza, Spain

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