Review
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Nephrol. May 6, 2015; 4(2): 160-168
Published online May 6, 2015. doi: 10.5527/wjn.v4.i2.160
Novel biomarkers of acute kidney injury: Evaluation and evidence in urologic surgery
Marianne Schmid, Deepansh Dalela, Rana Tahbaz, Jessica Langetepe, Marco Randazzo, Roland Dahlem, Margit Fisch, Quoc-Dien Trinh, Felix K-H Chun
Marianne Schmid, Deepansh Dalela, Quoc-Dien Trinh, Center for Surgery and Public Health and Division of Urologic Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, United States
Marianne Schmid, Rana Tahbaz, Jessica Langetepe, Roland Dahlem, Margit Fisch, Felix K-H Chun, Department of Urology, University Hospital Hamburg-Eppendorf, 20246 Hamburg, Germany
Deepansh Dalela, Center for Outcomes Research, Analytics and Evaluation, Vattikuti Urology Institute, Henry Ford Health System, Detroit, MI 48202, United States
Marco Randazzo, Department of Urology, Cantonal Hospital Aarau, 5000 Aarau, Switzerland
Author contributions: All authors of this paper have substantially participated in the planning, execution, and data interpretation of the study; in addition, they have written, read and approved the final version submitted; all the authors contributed to the study concept, design, acquisition, interpretation, drafting, critically revision for important intellectual content of the manuscript.
Conflict-of-interest: The authors have no conflict of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Felix K-H Chun, MD, Associate Professor of Urology, Department of Urology, University Hospital Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany. chun@uke.de
Telephone: +49-40-741053486
Received: July 16, 2014
Peer-review started: July 17, 2014
First decision: August 14, 2014
Revised: December 30, 2014
Accepted: January 15, 2015
Article in press: January 19, 2015
Published online: May 6, 2015

Abstract

Patients undergoing urologic surgery are at risk of acute kidney injury (AKI) and consequently long-term deterioration in renal function. AKI is further associated with significantly higher odds of perioperative complications, prolonged hospital stay, higher mortality and costs. Therefore, better awareness and detection of AKI, as well as identification of AKI determinants in the urological surgery setting is warranted to pre-empt and mitigate further deterioration of renal function in patients at special risk. New consensus criteria provide precise definitions of diagnosis and description of the severity of AKI. However, they rely on serum creatinine (SCr), which is known to be an inaccurate marker of early changes in renal function. Therefore, several new urinary and serum biomarkers promise to address the gap associated with the use of SCr. Novel biomarkers may complement SCr measurement or most likely improve the diagnostic accuracy of AKI when used in combinations. However, novel biomarkers have to prove their clinical applicability, accuracy, and cost effectiveness prior to implementation into clinical practice. Most preferably, novel biomarkers should help to positively improve a patient’s long-term renal functional outcomes. The purpose of this review is to discuss currently available biomarkers and to review their clinical evidence within urologic surgery settings.

Key Words: Acute kidney injury, Urology, Outcome, Renal function, Biomarker, Surgery

Core tip: Patients undergoing renal surgery represent a unique population at risk of acute kidney injury (AKI). AKI is known to be associated with adverse perioperative outcomes. Therefore, efforts are warranted to promote awareness for AKI. Novel biomarkers promise to improve early and accurate detection of AKI, which may help to provide better patients’ outcomes. However, these biomarkers still have to prove their clinical effectiveness prior to their implementation into urologic surgery settings.



INTRODUCTION

Urologic patients are at risk of acute kidney injury (AKI)[1-3]. A recent study evaluating procedure-dependent incidence of AKI in patients undergoing urologic surgery found that AKI was most frequently associated with partial/radical nephrectomy and nephroureterectomy (43.1%), transurethral resection of bladder tumor (15.3%), cystoprostatectomy (3.6%), ureteroscopic lithotripsy (3.6%), transurethral resection of the prostate (2.2%), radical prostatectomy (1.5%) and JJ-stent insertion (1.5%)[4].

Potentially reversible causes of AKI related to urologic surgery may be of pre- (e.g., postoperative bleeding, sepsis) or post-renal (e.g., urinary obstruction, dislocation of ureteric stent, anastomotic leak) origin. However, AKI observed in renal surgery patients is largely related to direct renal damage, resulting in a potentially irreversible decline of renal function. Although partial nephrectomy for renal cell carcinoma aims to preserve renal function, AKI following the direct removal of renal parenchyma and damage of the remaining tissue from hyperfiltration or ischemia is a commonly observed adverse event in these patients[5,6]. Besides the volume of preserved renal parenchyma, type and duration of ischemia during partial nephrectomy remain the most important modifiable factors for renal functional outcome[7].

Ischemic renal injury leads to a robust inflammatory response within the kidney, but also extrarenal manifestations have been observed[8-10]. Furthermore, the impact of renal ischemia-reperfusion injury on tumor propagation, malignant progression, and resistance to therapy is a topic of current investigations[11,12]. In addition, there is evidence demonstrating an impact of postoperative AKI on adverse surgical outcomes[13]. Indeed, AKI is associated with higher complication rates, longer hospital stays, increased mortality, and therefore greater utilization of health care resources and associated costs[14,15]. As patients undergoing urologic oncologic surgery often present with (unknown) pre-existing chronic kidney disease (CKD) at the time of surgery[16,17] an additional perioperative episode of AKI may contribute to worse renal recovery, long-term renal function deterioration and progression of CKD[3,18]. Consequently, urologists need to seek out the risk factors for AKI, identify the present signs and foresee its impact on the perioperative outcome of their patients[13].

While there are excellent reviews highlighting the most promising urinary and serum biomarkers of AKI[19,20], the purpose of this review is to discuss currently available biomarkers and to review their clinical evidence within urologic surgery settings.

DATA ACQUISITION

A non-systematic PubMed/Medline literature search was performed to identify original articles, review articles, and editorials evaluating AKI biomarkers in urologic surgery using the keywords “acute kidney injury, biomarkers, surgery, urology,” of the last 3 years (May 30, 2001 to July 31, 2014). The literature search was restricted to English language and availability of full text.

RESULTS
Definition and diagnosis of acute kidney injury

Due to a lack of consensus on the definition of acute renal failure, a wide variation exists in estimates of disease prevalence and mortality[15]. Currently, “AKI” is defined as an abrupt deterioration of kidney function and includes a spectrum ranging from minor renal functional impairment to acute renal failure requiring renal replacement therapy. The Risk, Injury, Failure, Loss, and End-stage kidney disease (RIFLE) staging criteria was the first consensus definition for AKI[21], followed by the Acute Kidney Injury Network (AKIN) classification, which defines AKI as an absolute increase in the serum creatinine (SCr) concentration of ≥ 0.3 mg/dL from baseline within 48 h[22]. More recently, the Kidney Disease/Improving Global Outcomes (KDIGO) group revised the definition of AKI, retaining AKIN staging criteria by classifying patients according to changes in SCr and urine output[23]. RIFLE, AKIN and KDIGO definitions have emphasized on the non-negligible incidence of AKI and its long-term adverse outcomes[21-23].

Biomarkers of acute kidney injury

Serum creatinine: SCr, is the gold-standard marker for renal function. However, SCr concentrations can be affected by age, gender, and racial differences of body mass as well as dietary factors and volume status[24]. In general, equations that estimate renal function, such as the Modification of Diet in Renal Disease or the Chronic Kidney Disease Epidemiology Collaboration equations[25,26], attempt to overcome the relative inaccuracy of SCr by including these patient characteristics to estimate glomerular filtration rate (GFR)[27]. Nonetheless SCr is primarily a marker of glomerular function, and SCr-based measurements may be inaccurate in detecting an abrupt decline in renal function, as the functional reserve of the remaining healthy nephrons prevents a significant rise in SCr until 50% of nephrons are lost[28,29]. Furthermore, the early phase of AKI is accompanied with few symptoms or may even be asymptomatic. Thus, it is critical to note that even if the SCr-based estimation of renal function is “normal”, loss of renal reserve may already have begun.

Consequently, recent research has focused on novel biomarkers that are directly related to the underlying renal injury and may diagnose AKI more expeditiously and accurately, while concurrently predicting its severity[30,31]. Most perioperative studies on AKI have been performed in the setting of cardiac surgery. However, as the awareness of AKI is increasing, other surgical specialties are evaluating this adverse outcome as well[32,33]. Additional biomarkers of AKI to rely on would be preferable especially in urologic high-risk patients (e.g., renal surgery, pre-existing CKD). In fact, several promising serum and urinary biomarkers are now available including serum and urinary Cystatin C (sCysC and uCysC), neutrophil gelatinase-associated lipocalin (sNGAL and uNGAL), and urinary Kidney Injury Molecule 1 (uKIM-1), Interleukin-18 (uIL-18), Liver-type fatty acid binding protein (uL-FABP) and N-acetyl-β-D-glucosaminidase (uNAG)[34]. However, these biomarkers are still under investigation: baseline values are often obtained from healthy volunteers and optimal cut-off values to define AKI need to be determined (Table 1). Some of these biomarkers already demonstrated additional prognostic value in the urologic surgery setting (Table 2), whereas others have yet to prove their clinical utility.

Table 1 Baseline reference values of novel biomarkers of acute kidney injury obtained from different studies.
BiomarkerInjurySourceTestUnitHealthy controls (range)
Cystatin CProximal tubule injurySerumNephelometric immunoassay/ELISAmg/L0.53-0.95[38]
0. 85 ± 0.21[39]
UrineNephelometric immunoassay/ELISAmg/L0.051-0.28[37]
0.02-0.11[96]
NGALIschemia and nephrotoxinsSerumELISAng/mL86.3 ± 43.0 (men)[54]
88.9 ± 38.2 (women)[54]
56.71 ± 17.57[39]
1.7 ± 0.5[55]
0.4-100[56]
UrineELISAng/mL5.7-17.7[55]
11.94 ± 8.09[39]
0.8-28.9 (men)[96]
1.9-316.7 (women)[96]
KIM-1Ischemia and nephrotoxinsUrineELISApg/mL59-2146[70]
395.1 ± 398.8[39]
31.0-1000.0[56]
31.0-1736.5[96]
IL-18Toxic, delayed graft functionUrineELISApg/mL1.4-1.8[80]
3.0-108.6[96]
6.2-311.1[96]
L-FABPIschemia and nephrotoxinsUrineELISAng/mL3-400[83]
μg/gCr5.67 (2.74-8.21)[87]
NAGTubule injuryUrineColorimetryU/g0.75-0.90 U/g[95]
1.06 ± 0.1 U/g (children)[90]
Table 2 Biomarkers of acute kidney injury evaluated within urologic surgery settings.
Ref.BiomarkerSourceCohortSurgical settingOutcomeComparisonTime
Langetepe et al[65]CysC, NGAL, KIM-1 CrUrine Serum31 RCC patientsPN, RNIncreased values of CysC, NGAL, KIM-1 NGAL significant correlation to Cr No advantage for earlier detection of renal injuryPre-/postoperative24 h after surgery
Sprenkle et al[63]NGALUrinePN: 88 patients, RN: 32 patients, thoracic surgery: 42 patientsPN, RN (warm or cold ischemia)No association between postoperative NGAL and any AKI AKI was not significantly associated with increased NGAL in PN patients No correlation with ischemia time Patients with eGFR < 60 mL/min per 1.73 m2 had higher NGAL postoperatively than those with an eGFR > 60 mL/min per 1.73 m2PN/RN /thoracic surgery patients4, 8, 12, 24 h post surgery
Parekh et al[62]Cr, NGAL, CysC NGAL, LFABP, NAG, KIM-1, IL-18Serum Urine, (renal biopsy)20 patients with renal massPN (warm or cold ischemia)Cr was significantly increased at 24 h CysC was not significantly changed at 2 or 24 h Significant increases serum NGAL at 2 and 24 h, increase of NGAL with increased ischemia time, no relation to peak Cr or morphology-score Early increases of L-FABP Early increase of NAG Increased NGAL at all times KIM-1maximally increased at 24 h IL-18 was increased at all time pointsCorrelation to renal biopsies (pre-, intra. postoperative)2 or 24 h after surgery
Schmid et al[50]Cr, CysCSerum31 RCC patientsPN, RNPostoperative Cysc and Cr elevations similarly predict renal function deterioration CysC-based GFR appears superior to eGFR in “Cr-blind” areaPre-/postoperative, 1 yr follow up24 h, 1 yr after surgery
Xue et al[76]Cr NGAL, KIM-1Serum Urine90 patients with obstructive uropathyNAKIM-1 and NGAL good accuracy for detecting AKI KIM-1 predicts the renal outcome 72 h postoperativelyPre-/postoperative4, 8, 12, 24, 48, 72 h after surgery
Cost et al[66]NGALUrine (bladder and renal pelvis)61 pediatric patients with ureteropelvic junction obstructionPyeloplastySignificantly increased bladder NGAL Inverse correlation of bladder and renal pelvic NGAL levels with the differential renal function of the affected kidneyHealthy childrenIntraoperative
Zekey et al[64]Cr NGALSerum Urine40 patients with kidney stonesSWLNo statistical Cr and urine NGAL levelsBefore/after interventionday 1, 2, 7 after intervention
Fahmy et al[74]KIM-1, NAGUrine60 patients with kidney stones (50 SWL, 10 URS)SWL, URSKIM-1 values were increased in patients with kidney stones when compared with volunteers KIM-1 and NAG levels significantly increased post-SWL Poor kidney function was significantly associated with increased KIM-1 and NAG baseline and post-SWL No significant change in urinary KIM-1 and NAG concentrations before and after URSVolunteers without kidney stones2-3 h after intervention
Ng et al[82]IL-18, NAGUrine206 patinets with renal stonesSWLIncreased IL-18 and NAG I slower shock wave delivery group60 vs 120 shock waves/minAfter intervention
Hatipoğlu et al[75]KIM-1 (free radical production)Urine30 patients with kidney stonesSWLSignificant increase of KIM-1Pre-/postoperative2 h after intervention
Novel biomarkers of acute kidney injury

Serum and urinary cystatin C: CysC is a low-molecular weight protein that is freely filtered across the glomerular membrane and in consequence less reliant on age, sex, race and muscle mass, compared to SCr[35]. Moreover, although CyC is not normally detected in the urine, it has been found in the urine of patients with tubular disease, suggesting its putative role as a marker of renal tubular damage[36]. Nephelometric measurements of CysC have upper reference values of 0.28 mg/L[37] in the urine and range between 0.53-0.95 mg/L in the serum of healthy individuals[38,39].

CysC has been proposed as a complementary or possibly marker of baseline renal function[35,40]. Although sCysC measurement is currently 10 times more expensive than SCr, it is implemented in routine renal function measurement of pediatric patients and used to monitor kidney transplant patients[41-43]. Furthermore, there is evidence suggesting that an elevation of sCysC predates minor decreases in GFR 1 to 2 d prior to symptoms, SCr elevation and/or renal function decline[40,44,45]. Early elevations of uCysC levels were significant predictors of AKI after elective cardiac surgery[46], and are correlated with the need for renal replacement therapy in patients with acute tubular necrosis[47]. However, other studies were not able to corroborate these findings[37] and suggest that sCysC is unreliable in the context of postrenal obstruction[48]. Yet, uCysC was shown to be independently associated with mortality in critically ill patients with AKI[49].

In patients undergoing partial or radical nephrectomy, elevations of both SCr and sCysC on postoperative day one predicted renal function deterioration one year after surgery, while sCysC correlated better to renal function estimates compared to SCr in the “SCr-blind” area[50].

Serum and urinary NGAL: Production of NGAL, a lipocalin protein involved in innate immunity by binding iron to limit bacterial growth[51], is upregulated following renal injury, and consequently detectable in serum and urine hours prior to functional changes[52,53]. sNGAL values in healthy individuals should be around 86.3 ng/mL in men and 88.9 ng/mL in women[39,54-56], but may increase > 10-fold in serum and > 100-fold in urine following an acute injury[57].

A meta-analysis of 19 observational studies including 2500 patients was performed to estimate the diagnostic and prognostic accuracy of NGAL for AKI detection and to establish the role of urinary and serum NGAL in the context of AKI[58]. Xin et al[59] showed that for patients undergoing cardiac surgery, an increase of sNGAL was not temporally different to the rise of SCr within 48 h after AKI, however uNGAL (and IL-18) significantly increased to a peak of 400 ng/mL within 2-4 h of AKI.

Induction of unilateral renal ischemia in animal models results in physiological changes of the ischemic and contralateral kidney, with a corresponding increase of uNGAL and decrease of renal function[60,61]. Parekh et al[62] studied the renal response to > 30 min of warm or cold clamp ischemia in patients undergoing partial nephrectomy and observed significant increases in sNGAL 2 and 24 h after surgery. While levels of all urinary biomarkers studied (NGAL, KIM-1, IL-18, NAG, L-FABP) increased 2 and/or 24 h after surgery, sCysC levels did not change significantly (SWL)[62]. Conversely, Sprenkle et al[63] did not observe increased uNGAL in partial nephrectomy patients within 24 h after surgery. Accordingly, no statistically significant change of uNGAL levels was observed in 40 nephrolithiasis patients treated with shock-wave lithotripsy[64]. Yet, our own data showed increased levels of uNGAL, KIM-1 and uCysC in 31 patients 24 h after partial or radical nephrectomy, but only uNGAL was correlated with SCr-based measurement of renal function[65]. Increased levels of uNGAL have also been obtained from bladder urine in children with ureteropelvic junction obstruction undergoing unilateral pyeloplasty[66]. Finally, uNGAL may serve as an early indicator for cisplatin nephrotoxicity[67], which may be useful for patients with muscle-invasive bladder undergoing neoadjuvant chemotherapy prior to radical cystectomy.

Urinary KIM-1: KIM-1 is a transmembrane glycoprotein undetectable in healthy kidney tissue, but it represents the most upregulated protein in proximal tubular cells after ischemic or nephrotoxic injury[68]. KIM-1 can be immediately detected in the urine following injury[69,70]. A strong correlation between immunohistochemical KIM-1 expression and tubular cell injury was shown in renal allograft biopsies of patients with active antibody-mediated transplant rejection[71], suggesting that KIM-1 is a reliable marker for tubular epithelial injury prior to elevated blood biochemical indexes and morphological changes. In addition, children with AKI following cardiac surgery demonstrated elevated uKIM-1 levels 12 h after surgery[72]. KIM-1 is measured in the urine by means of enzyme-linked immunosorbent assay, with normal values ranging between 59-2146 pg/mL in the healthy population[70,73].

A significant increase of uKIM-1 levels 2-3 h after SWL treatment[74,75] suggests direct ischemic damage and the release of free radicals. Both uKIM-1 and uNGAL demonstrated accuracy in detecting AKI among patients undergoing surgery for obstructive nephropathy; furthermore they might play a potential role in predicting postoperative renal recovery and long-term renal outcome[76,77].

Urinary IL-18: IL-18 is a pro-inflammatory cytokine that is activated in proximal tubule cells and excreted in the urine following a kidney injury. Increased expression of IL-18 genes has been demonstrated after renal ischemic injury[78]. Animal models revealed that IL-18 stimulates a positive feedback via IL-18 receptor during renal obstruction, which further stimulates IL-18 production and gene expression[79].

Initially described in the pediatric cardiac surgery setting, IL-18 the urine increased 6 h in after surgery, whereas SCr did not reveal AKI until 48-72 h after surgery[55]. Moreover, uIL-18 also increased significantly in adults and peaked at 600 pg/mL within 2-4 h after AKI[59]. Another study demonstrated an increase from 1.4 pg/mL to a peak of 234 pg/mL (about 25-fold) 12 h after cardiopulmonary bypass surgery in patients presenting AKI[55]. In patients with respiratory distress syndrome experiencing AKI, median uIL-18 was 104 pg/mL (range: 0 to 955 pg/mL), compared to 0 (range: 0 to 173 pg/mL) in control patients; IL-18 levels of > 100 pg/mL were associated with a 6.5-fold higher risk of AKI 24 h after hospitalization. Furthermore, higher level of uIL-18 (and serum IL-18) in ICU patients developing (dialysis-dependent) AKI was independently associated with mortality[80,81].

Finally, patients undergoing SWL showed a significant increase of uIL-18 (and uNAG) when treated with slower shock waves[82].

Urinary L-FABP: L-FABP is a 14-kDa protein expressed in proximal tubular epithelial cells. The urine of healthy individuals contains approximately 16 ng/mL L-FABP[83]. The gene responsible for L-FABP is associated with hypoxic stress. L-FABP binds unsaturated fatty acids and lipid peroxidation products during tissue injury from hypoxia[84]. Urinary excretion of L-FABP thus reflects stress within proximal tubular epithelial cells, and its correlation with renal function deterioration has been reported with AKI following contrast nephropathy and cardiac surgery[83,85]. Although uL-FABP may be a promising biomarker for early detection of AKI, as demonstrated in an animal model of ischemia-reperfusion[86], or for prediction of the need for dialysis and in-hospital mortality[87], its value in urologic surgery warrants further investigation.

NAG: NAG, a tubular lysosomal brush border enzyme, is released into the urine following (reversible) renal proximal tubule injury. NAG is elevated in the urine of children with chronic renal obstruction[88], regardless of the grade of hydronephrosis[89], and following AKI[90,91]. Rat models with isolated blunt renal trauma showed increased uNAG in the early stage after injury[92]. However, the clinical utility of NAG remains limited as the urinary excretion of this enzyme is also increased in glomerular diseases such as diabetic nephropathy[93]. The combination of urinary L-FABP (high sensitivity) and uNAG or uNGAL (high specificity) may enhance the detection of early postoperative AKI in patients undergoing cardiac surgery[94,95].

CONCLUSION

A plethora of novel biomarkers for AKI have recently been described. Whereas sCysC, uCysC, sNGAL, uNGAL, uKIM-1 and uNAG have shown promise, we did not find convincing evidence for uIL-18 and uL-FABP. However, from a clinical perspective current use of these biomarkers in the urologic surgery setting is rare. Notable reasons behind this are the limited availability of assays, additional cost and the (currently) poor sensitivity and specificity demonstrated in urologic patients. Consequently, until now none of these biomarkers has been able to allow early detection of AKI in a way that would positively improve a patient’s long-term outcomes and justify a regular implementation in specific urologic surgery settings. SCr remains the mainstay for evaluation of kidney function in urologic surgical patients. However, novel biomarkers may complement SCr measurement to indicate the need for urgent drainage or initiation of renoprotective measures. Moreover, it is likely that a combined use of these novel biomarkers will be needed to improve the diagnostic accuracy of AKI. Multiplex assays for simultaneous quantification of several biomarkers promise to overcome the flaws of single marker use and demonstrate the advantage of combinations reflecting different aspects of renal injury[96]. While these assays are currently more expensive compared to traditional SCr measurement, the hope is that the incremental diagnostic accuracy would offset costs by mitigating costly associated complications of AKI.

ACKNOWLEDGMENTS

Quoc-Dien Trinh is supported by the Professor Walter Morris-Hale Distinguished Chair in Urologic Oncology at the Brigham and Women’s Hospital.

Footnotes

P- Reviewer: Carvalho M, Papatsoris AG, Simmons MN S- Editor: Gong XM L- Editor: A E- Editor: Lu YJ

References
1.  Wang SJ, Mu XN, Zhang LY, Liu QY, Jin XB. The incidence and clinical features of acute kidney injury secondary to ureteral calculi. Urol Res. 2012;40:345-348.  [PubMed]  [DOI]
2.  Kim MJ, Bachmann A, Mihatsch MJ, Ruszat R, Sulser T, Mayr M. Acute renal failure after continuous flow irrigation in patients treated with potassium-titanyl-phosphate laser vaporization of prostate. Am J Kidney Dis. 2008;51:e19-e24.  [PubMed]  [DOI]
3.  Cho A, Lee JE, Kwon GY, Huh W, Lee HM, Kim YG, Kim DJ, Oh HY, Choi HY. Post-operative acute kidney injury in patients with renal cell carcinoma is a potent risk factor for new-onset chronic kidney disease after radical nephrectomy. Nephrol Dial Transplant. 2011;26:3496-3501.  [PubMed]  [DOI]
4.  Caddeo G, Williams ST, McIntyre CW, Selby NM. Acute kidney injury in urology patients: incidence, causes and outcomes. Nephrourol Mon. 2013;5:955-961.  [PubMed]  [DOI]
5.  Brenner BM, Lawler EV, Mackenzie HS. The hyperfiltration theory: a paradigm shift in nephrology. Kidney Int. 1996;49:1774-1777.  [PubMed]  [DOI]
6.  Lane BR, Babineau DC, Poggio ED, Weight CJ, Larson BT, Gill IS, Novick AC. Factors predicting renal functional outcome after partial nephrectomy. J Urol. 2008;180:2363-2368; discussion 2363-2368.  [PubMed]  [DOI]
7.  Becker F, Van Poppel H, Hakenberg OW, Stief C, Gill I, Guazzoni G, Montorsi F, Russo P, Stöckle M. Assessing the impact of ischaemia time during partial nephrectomy. Eur Urol. 2009;56:625-634.  [PubMed]  [DOI]
8.  Bonventre JV, Zuk A. Ischemic acute renal failure: an inflammatory disease? Kidney Int. 2004;66:480-485.  [PubMed]  [DOI]
9.  Hoke TS, Douglas IS, Klein CL, He Z, Fang W, Thurman JM, Tao Y, Dursun B, Voelkel NF, Edelstein CL. Acute renal failure after bilateral nephrectomy is associated with cytokine-mediated pulmonary injury. J Am Soc Nephrol. 2007;18:155-164.  [PubMed]  [DOI]
10.  Kramer AA, Postler G, Salhab KF, Mendez C, Carey LC, Rabb H. Renal ischemia/reperfusion leads to macrophage-mediated increase in pulmonary vascular permeability. Kidney Int. 1999;55:2362-2367.  [PubMed]  [DOI]
11.  Höckel M, Vaupel P. Tumor hypoxia: definitions and current clinical, biologic, and molecular aspects. J Natl Cancer Inst. 2001;93:266-276.  [PubMed]  [DOI]
12.  Skolarikos AA, Papatsoris AG, Alivizatos G, Deliveliotis C. Molecular pathogenetics of renal cancer. Am J Nephrol. 2006;26:218-231.  [PubMed]  [DOI]
13.  Schmid M, Abd-El-Barr AE, Gandaglia G, Sood A, Olugbade K, Ruhotina N, Sammon JD, Varda B, Chang SL, Kibel AS. Predictors of 30-day acute kidney injury following radical and partial nephrectomy for renal cell carcinoma. Urol Oncol. 2014;32:1259-1266.  [PubMed]  [DOI]
14.  Chertow GM, Soroko SH, Paganini EP, Cho KC, Himmelfarb J, Ikizler TA, Mehta RL. Mortality after acute renal failure: models for prognostic stratification and risk adjustment. Kidney Int. 2006;70:1120-1126.  [PubMed]  [DOI]
15.  Lameire NH, Bagga A, Cruz D, De Maeseneer J, Endre Z, Kellum JA, Liu KD, Mehta RL, Pannu N, Van Biesen W. Acute kidney injury: an increasing global concern. Lancet. 2013;382:170-179.  [PubMed]  [DOI]
16.  Lane BR, Poggio ED, Herts BR, Novick AC, Campbell SC. Renal function assessment in the era of chronic kidney disease: renewed emphasis on renal function centered patient care. J Urol. 2009;182:435-443; discussion 443-444.  [PubMed]  [DOI]
17.  Schmid M, Ravi P, Abd-El-Barr AE, Klap J, Sammon JD, Chang SL, Menon M, Kibel AS, Fisch M, Trinh QD. Chronic kidney disease and perioperative outcomes in urological oncological surgery. Int J Urol. 2014;21:1245-1252.  [PubMed]  [DOI]
18.  Ali T, Khan I, Simpson W, Prescott G, Townend J, Smith W, Macleod A. Incidence and outcomes in acute kidney injury: a comprehensive population-based study. J Am Soc Nephrol. 2007;18:1292-1298.  [PubMed]  [DOI]
19.  Lane BR. Molecular markers of kidney injury. Urol Oncol. 2013;31:682-685.  [PubMed]  [DOI]
20.  Slocum JL, Heung M, Pennathur S. Marking renal injury: can we move beyond serum creatinine? Transl Res. 2012;159:277-289.  [PubMed]  [DOI]
21.  Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P. Acute renal failure - definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care. 2004;8:R204-R212.  [PubMed]  [DOI]
22.  Mehta RL, Kellum JA, Shah SV, Molitoris BA, Ronco C, Warnock DG, Levin A. Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury. Crit Care. 2007;11:R31.  [PubMed]  [DOI]
23.  KDIGO AKI Working Group. KDIGO clinical practice guideline for acute kidney injury. Kidney Int Suppl. 2012;2:1-138.  [PubMed]  [DOI]
24.  Michels WM, Grootendorst DC, Verduijn M, Elliott EG, Dekker FW, Krediet RT. Performance of the Cockcroft-Gault, MDRD, and new CKD-EPI formulas in relation to GFR, age, and body size. Clin J Am Soc Nephrol. 2010;5:1003-1009.  [PubMed]  [DOI]
25.  Levey AS, Coresh J, Greene T, Marsh J, Stevens LA, Kusek JW, Van Lente F. Expressing the Modification of Diet in Renal Disease Study equation for estimating glomerular filtration rate with standardized serum creatinine values. Clin Chem. 2007;53:766-772.  [PubMed]  [DOI]
26.  Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF, Feldman HI, Kusek JW, Eggers P, Van Lente F, Greene T. A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150:604-612.  [PubMed]  [DOI]
27.  Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med. 1999;130:461-470.  [PubMed]  [DOI]
28.  Hayslett JP. Functional adaptation to reduction in renal mass. Physiol Rev. 1979;59:137-164.  [PubMed]  [DOI]
29.  Hostetter TH, Olson JL, Rennke HG, Venkatachalam MA, Brenner BM. Hyperfiltration in remnant nephrons: a potentially adverse response to renal ablation. J Am Soc Nephrol. 2001;12:1315-1325.  [PubMed]  [DOI]
30.  Coca SG, Yalavarthy R, Concato J, Parikh CR. Biomarkers for the diagnosis and risk stratification of acute kidney injury: a systematic review. Kidney Int. 2008;73:1008-1016.  [PubMed]  [DOI]
31.  Waikar SS, Bonventre JV. Biomarkers for the diagnosis of acute kidney injury. Nephron Clin Pract. 2008;109:c192-c197.  [PubMed]  [DOI]
32.  Dedeoglu B, de Geus HR, Fortrie G, Betjes MG. Novel biomarkers for the prediction of acute kidney injury in patients undergoing liver transplantation. Biomark Med. 2013;7:947-957.  [PubMed]  [DOI]
33.  Sung WC, Yu HP, Tsai YF, Chung PC, Lin CC, Lee WC. The ratio of plasma interleukin-18 is a sensitive biomarker for acute kidney injury after liver transplantation. Transplant Proc. 2014;46:816-817.  [PubMed]  [DOI]
34.  Thomas AA, Demirjian S, Lane BR, Simmons MN, Goldfarb DA, Subramanian VS, Campbell SC. Acute kidney injury: novel biomarkers and potential utility for patient care in urology. Urology. 2011;77:5-11.  [PubMed]  [DOI]
35.  Roos JF, Doust J, Tett SE, Kirkpatrick CM. Diagnostic accuracy of cystatin C compared to serum creatinine for the estimation of renal dysfunction in adults and children--a meta-analysis. Clin Biochem. 2007;40:383-391.  [PubMed]  [DOI]
36.  Conti M, Moutereau S, Zater M, Lallali K, Durrbach A, Manivet P, Eschwège P, Loric S. Urinary cystatin C as a specific marker of tubular dysfunction. Clin Chem Lab Med. 2006;44:288-291.  [PubMed]  [DOI]
37.  Royakkers AA, van Suijlen JD, Hofstra LS, Kuiper MA, Bouman CS, Spronk PE, Schultz MJ. Serum cystatin C-A useful endogenous marker of renal function in intensive care unit patients at risk for or with acute renal failure? Curr Med Chem. 2007;14:2314-2317.  [PubMed]  [DOI]
38.  Croda-Todd MT, Soto-Montano XJ, Hernández-Cancino PA, Juárez-Aguilar E. Adult cystatin C reference intervals determined by nephelometric immunoassay. Clin Biochem. 2007;40:1084-1087.  [PubMed]  [DOI]
39.  Matys U, Bachorzewska-Gajewska H, Malyszko J, Dobrzycki S. Assessment of kidney function in diabetic patients. Is there a role for new biomarkers NGAL, cystatin C and KIM-1? Adv Med Sci. 2013;58:353-361.  [PubMed]  [DOI]
40.  Dharnidharka VR, Kwon C, Stevens G. Serum cystatin C is superior to serum creatinine as a marker of kidney function: a meta-analysis. Am J Kidney Dis. 2002;40:221-226.  [PubMed]  [DOI]
41.  Le Bricon T, Thervet E, Benlakehal M, Bousquet B, Legendre C, Erlich D. Changes in plasma cystatin C after renal transplantation and acute rejection in adults. Clin Chem. 1999;45:2243-2249.  [PubMed]  [DOI]
42.  Ayub S, Zafar MN, Aziz T, Iqbal T, Khan S, Rizvi SA. Evaluation of renal function by cystatin C in renal transplant recipients. Exp Clin Transplant. 2014;12:37-40.  [PubMed]  [DOI]
43.  Fox JA, Dudley AG, Bates C, Cannon GM. Cystatin C as a marker of early renal insufficiency in children with congenital neuropathic bladder. J Urol. 2014;191:1602-1607.  [PubMed]  [DOI]
44.  Herget-Rosenthal S, Marggraf G, Hüsing J, Göring F, Pietruck F, Janssen O, Philipp T, Kribben A. Early detection of acute renal failure by serum cystatin C. Kidney Int. 2004;66:1115-1122.  [PubMed]  [DOI]
45.  Pirgakis KM, Makris K, Dalainas I, Lazaris AM, Maltezos CK, Liapis CD. Urinary cystatin C as an early biomarker of acute kidney injury after open and endovascular abdominal aortic aneurysm repair. Ann Vasc Surg. 2014;28:1649-1658.  [PubMed]  [DOI]
46.  Koyner JL, Bennett MR, Worcester EM, Ma Q, Raman J, Jeevanandam V, Kasza KE, O’Connor MF, Konczal DJ, Trevino S. Urinary cystatin C as an early biomarker of acute kidney injury following adult cardiothoracic surgery. Kidney Int. 2008;74:1059-1069.  [PubMed]  [DOI]
47.  Herget-Rosenthal S, Poppen D, Hüsing J, Marggraf G, Pietruck F, Jakob HG, Philipp T, Kribben A. Prognostic value of tubular proteinuria and enzymuria in nonoliguric acute tubular necrosis. Clin Chem. 2004;50:552-558.  [PubMed]  [DOI]
48.  Hasslacher J, Lehner GF, Joannidis M. Insufficient performance of serum cystatin C as a biomarker for acute kidney injury of postrenal etiology. Intensive Care Med. 2012;38:170-171.  [PubMed]  [DOI]
49.  Nejat M, Pickering JW, Walker RJ, Westhuyzen J, Shaw GM, Frampton CM, Endre ZH. Urinary cystatin C is diagnostic of acute kidney injury and sepsis, and predicts mortality in the intensive care unit. Crit Care. 2010;14:R85.  [PubMed]  [DOI]
50.  Schmid M, Schwaiger B, Tenschert W, Shaffu M, Thabaz R, Langetepe J, Ahyai S, Eichelberg C, Fisch M, Chun F. Surveillance of renal function after (partial) tumor nephrectomy by Cystatin C-measurement. J Urol. 2013;189:Supplement e1-e952.  [PubMed]  [DOI]
51.  Yang J, Goetz D, Li JY, Wang W, Mori K, Setlik D, Du T, Erdjument-Bromage H, Tempst P, Strong R. An iron delivery pathway mediated by a lipocalin. Mol Cell. 2002;10:1045-1056.  [PubMed]  [DOI]
52.  Mishra J, Ma Q, Prada A, Mitsnefes M, Zahedi K, Yang J, Barasch J, Devarajan P. Identification of neutrophil gelatinase-associated lipocalin as a novel early urinary biomarker for ischemic renal injury. J Am Soc Nephrol. 2003;14:2534-2543.  [PubMed]  [DOI]
53.  Borregaard N, Cowland JB. Neutrophil gelatinase-associated lipocalin, a siderophore-binding eukaryotic protein. Biometals. 2006;19:211-215.  [PubMed]  [DOI]
54.  Stejskal D, Karpísek M, Humenanska V, Hanulova Z, Stejskal P, Kusnierova P, Petzel M. Lipocalin-2: development, analytical characterization, and clinical testing of a new ELISA. Horm Metab Res. 2008;40:381-385.  [PubMed]  [DOI]
55.  Parikh CR, Mishra J, Thiessen-Philbrook H, Dursun B, Ma Q, Kelly C, Dent C, Devarajan P, Edelstein CL. Urinary IL-18 is an early predictive biomarker of acute kidney injury after cardiac surgery. Kidney Int. 2006;70:199-203.  [PubMed]  [DOI]
56.  TECOmedical Group, Switzerland. Novel kidney injury biomarkers.  Available from: http: //www.tecomedical.com.  [PubMed]  [DOI]
57.  Mori K, Lee HT, Rapoport D, Drexler IR, Foster K, Yang J, Schmidt-Ott KM, Chen X, Li JY, Weiss S. Endocytic delivery of lipocalin-siderophore-iron complex rescues the kidney from ischemia-reperfusion injury. J Clin Invest. 2005;115:610-621.  [PubMed]  [DOI]
58.  Haase M, Bellomo R, Devarajan P, Schlattmann P, Haase-Fielitz A. Accuracy of neutrophil gelatinase-associated lipocalin (NGAL) in diagnosis and prognosis in acute kidney injury: a systematic review and meta-analysis. Am J Kidney Dis. 2009;54:1012-1024.  [PubMed]  [DOI]
59.  Xin C, Yulong X, Yu C, Changchun C, Feng Z, Xinwei M. Urine neutrophil gelatinase-associated lipocalin and interleukin-18 predict acute kidney injury after cardiac surgery. Ren Fail. 2008;30:904-913.  [PubMed]  [DOI]
60.  Silberstein JL, Sprenkle PC, Su D, Power NE, Tarin TV, Ezell P, Sjoberg DD, Feifer A, Fleisher M, Russo P. Neutrophil gelatinase-associated lipocalin (NGAL) levels in response to unilateral renal ischaemia in a novel pilot two-kidney porcine model. BJU Int. 2013;112:517-525.  [PubMed]  [DOI]
61.  Woodson BW, Wang L, Mandava S, Lee BR. Urinary cystatin C and NGAL as early biomarkers for assessment of renal ischemia-reperfusion injury: a serum marker to replace creatinine? J Endourol. 2013;27:1510-1515.  [PubMed]  [DOI]
62.  Parekh DJ, Weinberg JM, Ercole B, Torkko KC, Hilton W, Bennett M, Devarajan P, Venkatachalam MA. Tolerance of the human kidney to isolated controlled ischemia. J Am Soc Nephrol. 2013;24:506-517.  [PubMed]  [DOI]
63.  Sprenkle PC, Wren J, Maschino AC, Feifer A, Power N, Ghoneim T, Sternberg I, Fleisher M, Russo P. Urine neutrophil gelatinase-associated lipocalin as a marker of acute kidney injury after kidney surgery. J Urol. 2013;190:159-164.  [PubMed]  [DOI]
64.  Zekey F, Senkul T, Ates F, Soydan H, Yilmaz O, Baykal K. Evaluation of the impact of shock wave lithotripsy on kidneys using a new marker: how do neutrophil gelatinese-associated lypocalin values change after shock wave lithotripsy? Urology. 2012;80:267-272.  [PubMed]  [DOI]
65.  Langetepe J, Schmid M, Schwaiger B, Tahbaz R, Ahyai S, Eichelberg C, Fisch M, Chun F. Serum and urine biomarker profile of kidney injury after (partial) tumor nephrectomy.  Available from: http: //www.uroweb.org/events/abstracts-online/?AID=51341.  [PubMed]  [DOI]
66.  Cost NG, Noh PH, Devarajan P, Ivancic V, Reddy PP, Minevich E, Bennett M, Haffner C, Schulte M, DeFoor WR. Urinary NGAL levels correlate with differential renal function in patients with ureteropelvic junction obstruction undergoing pyeloplasty. J Urol. 2013;190:1462-1467.  [PubMed]  [DOI]
67.  Mishra J, Mori K, Ma Q, Kelly C, Barasch J, Devarajan P. Neutrophil gelatinase-associated lipocalin: a novel early urinary biomarker for cisplatin nephrotoxicity. Am J Nephrol. 2004;24:307-315.  [PubMed]  [DOI]
68.  Bonventre JV. Kidney injury molecule-1: a translational journey. Trans Am Clin Climatol Assoc. 2014;125:293-299; discussion 299.  [PubMed]  [DOI]
69.  Devarajan P. Biomarkers for the early detection of acute kidney injury. Curr Opin Pediatr. 2011;23:194-200.  [PubMed]  [DOI]
70.  Vaidya VS, Ramirez V, Ichimura T, Bobadilla NA, Bonventre JV. Urinary kidney injury molecule-1: a sensitive quantitative biomarker for early detection of kidney tubular injury. Am J Physiol Renal Physiol. 2006;290:F517-F529.  [PubMed]  [DOI]
71.  Song L, Xue L, Yu J, Zhao J, Zhang W, Fu Y. Kidney injury molecule-1 expression is closely associated with renal allograft damage. Bosn J Basic Med Sci. 2013;13:170-174.  [PubMed]  [DOI]
72.  Han WK, Waikar SS, Johnson A, Betensky RA, Dent CL, Devarajan P, Bonventre JV. Urinary biomarkers in the early diagnosis of acute kidney injury. Kidney Int. 2008;73:863-869.  [PubMed]  [DOI]
73.  Chaturvedi S, Farmer T, Kapke GF. Assay validation for KIM-1: human urinary renal dysfunction biomarker. Int J Biol Sci. 2009;5:128-134.  [PubMed]  [DOI]
74.  Fahmy N, Sener A, Sabbisetti V, Nott L, Lang RM, Welk BK, Méndez-Probst CE, MacPhee RA, VanEerdewijk S, Cadieux PA. Urinary expression of novel tissue markers of kidney injury after ureteroscopy, shockwave lithotripsy, and in normal healthy controls. J Endourol. 2013;27:1455-1462.  [PubMed]  [DOI]
75.  Hatipoğlu NK, Evliyaoğlu O, Işık B, Bodakçi MN, Bozkurt Y, Sancaktutar AA, Söylemez H, Atar M, Penbegül N, Yünce M. Antioxidant signal and kidney injury molecule-1 levels in shockwave lithotripsy induced kidney injury. J Endourol. 2014;28:224-228.  [PubMed]  [DOI]
76.  Xue W, Xie Y, Wang Q, Xu W, Mou S, Ni Z. Diagnostic performance of urinary kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin for acute kidney injury in an obstructive nephropathy patient. Nephrology (Carlton). 2014;19:186-194.  [PubMed]  [DOI]
77.  Lucarelli G, Mancini V, Galleggiante V, Rutigliano M, Vavallo A, Battaglia M, Ditonno P. Emerging urinary markers of renal injury in obstructive nephropathy. Biomed Res Int. 2014;2014:303298.  [PubMed]  [DOI]
78.  Supavekin S, Zhang W, Kucherlapati R, Kaskel FJ, Moore LC, Devarajan P. Differential gene expression following early renal ischemia/reperfusion. Kidney Int. 2003;63:1714-1724.  [PubMed]  [DOI]
79.  VanderBrink BA, Asanuma H, Hile K, Zhang H, Rink RC, Meldrum KK. Interleukin-18 stimulates a positive feedback loop during renal obstruction via interleukin-18 receptor. J Urol. 2011;186:1502-1508.  [PubMed]  [DOI]
80.  Parikh CR, Abraham E, Ancukiewicz M, Edelstein CL. Urine IL-18 is an early diagnostic marker for acute kidney injury and predicts mortality in the intensive care unit. J Am Soc Nephrol. 2005;16:3046-3052.  [PubMed]  [DOI]
81.  Lin CY, Chang CH, Fan PC, Tian YC, Chang MY, Jenq CC, Hung CC, Fang JT, Yang CW, Chen YC. Serum interleukin-18 at commencement of renal replacement therapy predicts short-term prognosis in critically ill patients with acute kidney injury. PLoS One. 2013;8:e66028.  [PubMed]  [DOI]
82.  Ng CF, Lo AK, Lee KW, Wong KT, Chung WY, Gohel D. A prospective, randomized study of the clinical effects of shock wave delivery for unilateral kidney stones: 60 versus 120 shocks per minute. J Urol. 2012;188:837-842.  [PubMed]  [DOI]
83.  Matsui K, Kamijo-Ikemori A, Sugaya T, Yasuda T, Kimura K. Usefulness of urinary biomarkers in early detection of acute kidney injury after cardiac surgery in adults. Circ J. 2012;76:213-220.  [PubMed]  [DOI]
84.  Bennaars-Eiden A, Higgins L, Hertzel AV, Kapphahn RJ, Ferrington DA, Bernlohr DA. Covalent modification of epithelial fatty acid-binding protein by 4-hydroxynonenal in vitro and in vivo. Evidence for a role in antioxidant biology. J Biol Chem. 2002;277:50693-50702.  [PubMed]  [DOI]
85.  Manabe K, Kamihata H, Motohiro M, Senoo T, Yoshida S, Iwasaka T. Urinary liver-type fatty acid-binding protein level as a predictive biomarker of contrast-induced acute kidney injury. Eur J Clin Invest. 2012;42:557-563.  [PubMed]  [DOI]
86.  Yamamoto T, Noiri E, Ono Y, Doi K, Negishi K, Kamijo A, Kimura K, Fujita T, Kinukawa T, Taniguchi H. Renal L-type fatty acid--binding protein in acute ischemic injury. J Am Soc Nephrol. 2007;18:2894-2902.  [PubMed]  [DOI]
87.  Susantitaphong P, Siribamrungwong M, Doi K, Noiri E, Terrin N, Jaber BL. Performance of urinary liver-type fatty acid-binding protein in acute kidney injury: a meta-analysis. Am J Kidney Dis. 2013;61:430-439.  [PubMed]  [DOI]
88.  Carr MC, Peters CA, Retik AB, Mandell J. Urinary levels of the renal tubular enzyme N-acetyl-beta-D-glucosaminidase in unilateral obstructive uropathy. J Urol. 1994;151:442-445.  [PubMed]  [DOI]
89.  Skalova S, Rejtar P, Kutilek S. Increased urinary N-acetyl-beta-D-glucosaminidase activity in children with hydronephrosis. Int Braz J Urol. 2007;33:80-83; discussion 84-86.  [PubMed]  [DOI]
90.  Bernard AM, Vyskocil AA, Mahieu P, Lauwerys RR. Assessment of urinary retinol-binding protein as an index of proximal tubular injury. Clin Chem. 1987;33:775-779.  [PubMed]  [DOI]
91.  Liangos O, Perianayagam MC, Vaidya VS, Han WK, Wald R, Tighiouart H, MacKinnon RW, Li L, Balakrishnan VS, Pereira BJ. Urinary N-acetyl-beta-(D)-glucosaminidase activity and kidney injury molecule-1 level are associated with adverse outcomes in acute renal failure. J Am Soc Nephrol. 2007;18:904-912.  [PubMed]  [DOI]
92.  Hanbeyoğlu A, Kazez A, Ustündağ B, Akpolat N. Determination of urinary N-acetyl-ß-D glucosaminidase (NAG) levels in experimental blunt renal trauma. Ulus Travma Acil Cerrahi Derg. 2011;17:475-481.  [PubMed]  [DOI]
93.  Marchewka Z, Kuźniar J, Długosz A. Enzymuria and beta2-mikroglobulinuria in the assessment of the influence of proteinuria on the progression of glomerulopathies. Int Urol Nephrol. 2001;33:673-676.  [PubMed]  [DOI]
94.  Katagiri D, Doi K, Honda K, Negishi K, Fujita T, Hisagi M, Ono M, Matsubara T, Yahagi N, Iwagami M. Combination of two urinary biomarkers predicts acute kidney injury after adult cardiac surgery. Ann Thorac Surg. 2012;93:577-583.  [PubMed]  [DOI]
95.  Liu S, Che M, Xue S, Xie B, Zhu M, Lu R, Zhang W, Qian J, Yan Y. Urinary L-FABP and its combination with urinary NGAL in early diagnosis of acute kidney injury after cardiac surgery in adult patients. Biomarkers. 2013;18:95-101.  [PubMed]  [DOI]
96.  Zhang X, Gibson B, Mori R, Snow-Lisy D, Yamaguchi Y, Campbell SC, Simmons MN, Daly TM. Analytical and biological validation of a multiplex immunoassay for acute kidney injury biomarkers. Clin Chim Acta. 2013;415:88-93.  [PubMed]  [DOI]