Biomarkers of acute kidney injury

Jeffrey C Sirota, Jelena Klawitter, Charles L Edelstein, Jeffrey C Sirota, Jelena Klawitter, Charles L Edelstein

Abstract

Acute kidney injury (AKI) is a common problem in both the inpatient and outpatient setting and often results from drug toxicities. Traditional methods of identifying AKI, through measurement of blood urea nitrogen and serum creatinine, are problematic in that they are slow to detect decreases in glomerular filtration rate (GFR) and are influenced by a variety of factors that are not related to GFR changes. The problems inherent in a creatinine-based diagnosis of AKI have impeded the development of proper therapeutics in AKI and posed problems in evaluating nephrotoxicity of drugs and other chemical exposures. In recent years, a number of new biomarkers of AKI with more favorable test characteristics than creatinine have been identified and studied in a variety of experimental and clinical settings. This review will consider the most well-established biomarkers and appraise the literature, with particular attention given to the use of biomarkers in identifying toxin-mediated AKI.

References

    1. Lameire N, van Biesen W, Vanholder R. The changing epidemiology of acute renal failure. Nature Clinical Practice Nephrology. 2006;2(7):364–377.
    1. Ympa YP, Sakr Y, Reinhart K, Vincent JL. Has mortality from acute renal failure decreased? A systematic review of the literature. American Journal of Medicine. 2005;118(8):827–832.
    1. Stevens LA, Levey AS. Measurement of kidney function. Medical Clinics of North America. 2005;89(3):457–473.
    1. Kassirer JP. Clinical evaluation of kidney function–glomerular function. The New England Journal of Medicine. 1971;285(7):385–389.
    1. Bagshaw SM, Gibney RTN. Conventional markers of kidney function. Critical Care Medicine. 2008;36(4):S152–S158.
    1. Stevens LA, Lafayette RA, Perrone RD, Levey AS. Laboratory evaluation of kidney function. In: Schrier RW, editor. Diseases of the Kidney and Urinary Tract. 8th edition. Philadelphia, Pa, USA: Lippincott Williams & Wilkins; 2007. pp. 299–336.
    1. Star RA. Treatment of acute renal failure. Kidney International. 1998;54(6):1817–1831.
    1. Moran SM, Myers BD. Course of acute renal failure studied by a model of creatinine kinetics. Kidney International. 1985;27(6):928–937.
    1. Shemesh O, Golbetz H, Kriss JP, Myers BD. Limitations of creatinine as a filtration marker in glomerulopathic patients. Kidney International. 1985;28(5):830–838.
    1. Wishart DS. Metabolomics: the principles and potential applications to transplantation. American Journal of Transplantation. 2005;5(12):2814–2820.
    1. Wishart D. Metabolomics: a complementary tool in renal transplantation. Contributions to Nephrology. 2008;160:76–87.
    1. Shockcor JP, Holmes E. Metabonomic applications in toxicity screening and disease diagnosis. Current Topics in Medicinal Chemistry. 2002;2(1):35–51.
    1. Niemann CU, Serkova NJ. Biochemical mechanisms of nephrotoxicity: application for metabolomics. Expert Opinion on Drug Metabolism and Toxicology. 2007;3(4):527–544.
    1. Boudonck KJ, Mitchell MW, Német L, et al. Discovery of metabolomics biomarkers for early detection of nephrotoxicity. Toxicologic Pathology. 2009;37(3):280–292.
    1. Serkova NJ, Niemann CU. Pattern recognition and biomarker validation using quantitative 1H-NMR-based metabolomics. Expert Review of Molecular Diagnostics. 2006;6(5):717–731.
    1. Mishra J, Dent C, Tarabishi R, et al. Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery. The Lancet. 2005;365(9466):1231–1238.
    1. Dent CL, Ma Q, Dastrala S, et al. Plasma neutrophil gelatinase-associated lipocalin predicts acute kidney injury, morbidity and mortality after pediatric cardiac surgery: a prospective uncontrolled cohort study. Critical Care. 2007;11(6):p. R127.
    1. Parikh CR, Mishra J, Thiessen-Philbrook H, et al. Urinary IL-18 is an early predictive biomarker of acute kidney injury after cardiac surgery. Kidney International. 2006;70(1):199–203.
    1. Parikh CR, Devarajan P, Zappitelli M, et al. Postoperative biomarkers predict acute kidney injury and poor outcomes after pediatric cardiac surgery. Journal of the American Society of Nephrology. 2011;22(9):p. 1737.
    1. Wagener G, Jan M, Kim M, et al. Association between increases in urinary neutrophil gelatinase-associated lipocalin and acute renal dysfunction after adult cardiac surgery. Anesthesiology. 2006;105(3):485–491.
    1. Haase-Fielitz A, Bellomo R, Devarajan P, et al. Novel and conventional serum biomarkers predicting acute kidney injury in adult cardiac surgery—a prospective cohort study. Critical Care Medicine. 2009;37(2):553–560.
    1. Haase-Fielitz A, Bellomo R, Devarajan P, et al. The predictive performance of plasma neutrophil gelatinase-associated lipocalin (NGAL) increases with grade of acute kidney injury. Nephrology Dialysis Transplantation. 2009;24(11):3349–3354.
    1. Haase M, Bellomo R, Devarajan P, et al. Novel biomarkers early predict the severity of acute kidney injury after cardiac surgery in adults. Annals of Thoracic Surgery. 2009;88(1):124–130.
    1. Tuladhar SM, Püntmann VO, Soni M, Punjabi PP, Bogle RG. Rapid detection of acute kidney injury by plasma and urinary neutrophil gelatinase-associated lipocalin after cardiopulmonary bypass. Journal of Cardiovascular Pharmacology. 2009;53(3):261–266.
    1. 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. Renal Failure. 2008;30(9):904–913.
    1. Haase M, Bellomo R, Story D, Davenport P, Haase-Fielitz A. Urinary interleukin-18 does not predict acute kidney injury after adult cardiac surgery: a prospective observational cohort study. Critical Care. 2008;12(4):p. R96.
    1. Han WK, Wagener G, Zhu Y, Wang S, Lee HT. Urinary biomarkers in the early detection of acute kidney injury after cardiac surgery. Clinical Journal of the American Society of Nephrology. 2009;4(5):873–882.
    1. Koyner JL, Vaidya VS, Bennett MR, et al. Urinary biomarkers in the clinical prognosis and early detection of acute kidney injury. Clinical Journal of the American Society of Nephrology. 2010;5(12):2154–2165.
    1. Koyner JL, Bennett MR, Worcester EM, et al. Urinary cystatin C as an early biomarker of acute kidney injury following adult cardiothoracic surgery. Kidney International. 2008;74(8):1059–1069.
    1. Nejat M, Pickering JW, Walker RJ, et al. Urinary cystatin C is diagnostic of acute kidney injury and sepsis, and predicts mortality in the intensive care unit. Critical Care. 2010;14(3):p. R85.
    1. Zappitelli M, Washburn KK, Arikan AA, et al. Urine neutrophil gelatinase-associated lipocalin is an early marker of acute kidney injury in critically ill children: a prospective cohort study. Critical Care. 2007;11(4):p. R84.
    1. Wheeler DS, Devarajan P, Ma Q, et al. Serum neutrophil gelatinase-associated lipocalin (NGAL) as a marker of acute kidney injury in critically ill children with septic shock. Critical Care Medicine. 2008;36(4):1297–1303.
    1. Washburn KK, Zappitelli M, Arikan AA, et al. Urinary interleukin-18 is an acute kidney injury biomarker in critically ill children. Nephrology Dialysis Transplantation. 2008;23(2):566–572.
    1. Du Y, Zappitelli M, Mian A, et al. Urinary biomarkers to detect acute kidney injury in the pediatric emergency center. Pediatric Nephrology. 2011;26(2):267–274.
    1. Constantin JM, Futier E, Perbet S, et al. Plasma neutrophil gelatinase-associated lipocalin is an early marker of acute kidney injury in adult critically ill patients: a prospective study. Journal of Critical Care. 2010;25(1):176.e1–176.e6.
    1. Mårtensson J, Bell M, Oldner A, Xu S, Venge P, Martling CR. Neutrophil gelatinase-associated lipocalin in adult septic patients with and without acute kidney injury. Intensive Care Medicine. 2010;36(8):1333–1340.
    1. Cruz DN, de Cal M, Garzotto F, et al. Plasma neutrophil gelatinase-associated lipocalin is an early biomarker for acute kidney injury in an adult ICU population. Intensive Care Medicine. 2010;36(3):444–451.
    1. Liangos O, Perianayagam MC, Vaidya VS, et al. Urinary N-acetyl-β-(D)-glucosaminidase activity and kidney injury molecule-1 level are associated with adverse outcomes in acute renal failure. Journal of the American Society of Nephrology. 2007;18(3):904–912.
    1. Szeto CC, Kwan BCH, Lai KB, et al. Urinary expression of kidney injury markers in renal transplant recipients. Clinical Journal of the American Society of Nephrology. 2010;5(12):2329–2337.
    1. Hall IE, Koyner JL, Doshi MD, Marcus RJ, Parikh CR. Urine cystatin C as a biomarker of proximal tubular function immediately after kidney transplantation. American Journal of Nephrology. 2011;33(5):407–413.
    1. Hirsch R, Dent C, Pfriem H, et al. NGAL is an early predictive biomarker of contrast-induced nephropathy in children. Pediatric Nephrology. 2007;22(12):2089–2095.
    1. Bachorzewska-Gajewska H, Malyszko J, Sitniewska E, Malyszko JS, Dobrzycki S. Neutrophil-gelatinase-associated lipocalin and renal function after percutaneous coronary interventions. American Journal of Nephrology. 2006;26(3):287–292.
    1. 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. American Journal of Kidney Diseases. 2009;54(6):1012–1024.
    1. Gul CB, Gullulu M, Oral B, et al. Urinary IL-18: a marker of contrast-induced nephropathy following percutaneous coronary intervention? Clinical Biochemistry. 2008;41(7-8):544–547.
    1. Ling W, Zhaohui N, Ben H, et al. Urinary IL-18 and NGAL as early predictive biomarkers in contrast-induced nephropathy after coronary angiography. Nephron—Clinical Practice. 2008;108(3):c176–c181.
    1. Mishra J, Mori K, Ma Q, Kelly C, Barasch J, Devarajan P. Neutrophil gelatinase-associated lipocalin: a novel early urinary biomarker for cisplatin nephrotoxicity. American Journal of Nephrology. 2004;24(3):307–315.
    1. 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. American Journal of Physiology—Renal Physiology. 2006;290(2):F517–F529.
    1. Ichimura T, Hung CC, Yang SA, Stevens JL, Bonventre JV. Kidney injury molecule-1: a tissue and urinary biomarker for nephrotoxicant-induced renal injury. American Journal of Physiology—Renal Physiology. 2004;286(3):F552–F563.
    1. Togashi Y, Sakaguchi Y, Miyamoto M, Miyamoto Y. Urinary cystatin C as a biomarker for acute kidney injury and its immunohistochemical localization in kidney in the CDDP-treated rats. Experimental and Toxicologic Pathology. In press.
    1. Gaspari F, Cravedi P, Mandalà M, et al. Predicting cisplatin-induced acute kidney injury by urinary neutrophil gelatinase-associated lipocalin excretion: a pilot prospective case-control study. Nephron—Clinical Practice. 2010;115(2):c154–c160.
    1. Negishi K, Noiri E, Doi K, et al. Monitoring of urinary L-type fatty acid-binding protein predicts histological severity of acute kidney injury. American Journal of Pathology. 2009;174(4):1154–1159.
    1. Schmidt-Ott KM, Mori K, Jau YL, et al. Dual action of neutrophil gelatinase-associated lipocalin. Journal of the American Society of Nephrology. 2007;18(2):407–413.
    1. Mishra J, Ma Q, Prada A, et al. Identification of neutrophil gelatinase-associated lipocalin as a novel early urinary biomarker for ischemic renal injury. Journal of the American Society of Nephrology. 2003;14(10):2534–2543.
    1. Alvelos M, Pimentel R, Pinho E, et al. Neutrophil gelatinase-associated lipocalin in the diagnosis of type 1 cardio-renal syndrome in the general ward. Clinical Journal of the American Society of Nephrology. 2011;6(3):476–481.
    1. Portal AJ, McPhail MJW, Bruce M, et al. Neutrophil gelatinase—associated lipocalin predicts acute kidney injury in patients undergoing liver transplantation. Liver Transplantation. 2010;16(11):1257–1266.
    1. Nickolas TL, O’Rourke MJ, Yang J, et al. Sensitivity and specificity of a single emergency department measurement of urinary neutrophil gelatinase-associated lipocalin for diagnosing acute kidney injury. Annals of Internal Medicine. 2008;148(11):810–819.
    1. Makris K, Markou N, Evodia E, et al. Urinary neutrophil gelatinase-associated lipocalin (NGAL) as an early marker of acute kidney injury in critically ill multiple trauma patients. Clinical Chemistry and Laboratory Medicine. 2009;47(1):79–82.
    1. de Geus HRH, Bakker J, Lesaffre EMEH, Le Noble JLML. Neutrophil gelatinase-associated lipocalin at ICU admission predicts for acute kidney injury in adult patients. American Journal of Respiratory and Critical Care Medicine. 2011;183(7):907–914.
    1. Singer E, Elger A, Elitok S, et al. Urinary neutrophil gelatinase-associated lipocalin distinguishes pre-renal from intrinsic renal failure and predicts outcomes. Kidney International. 2011;80:405–414.
    1. Melnikov VY, Ecder T, Fantuzzi G, et al. Impaired IL-18 processing protects caspase-1-deficient mice from ischemic acute renal failure. Journal of Clinical Investigation. 2001;107(9):1145–1152.
    1. Melnikov VY, Faubel S, Siegmund B, Scott Lucia M, Ljubanovic D, Edelstein CL. Neutrophil-independent mechanisms of caspase-1- and IL-18-mediated ischemic acute tubular necrosis in mice. Journal of Clinical Investigation. 2002;110(8):1083–1091.
    1. He Z, Lu L, Altmann C, et al. Interleukin-18 binding protein transgenic mice are protected against ischemic acute kidney injury. American Journal of Physiology—Renal Physiology. 2008;295(5):F1414–F1421.
    1. Wu H, Craft ML, Wang P, et al. IL-18 contributes to renal damage after ischemia-reperfusion. Journal of the American Society of Nephrology. 2008;19(12):2331–2341.
    1. Edelstein CL, Hoke TS, Somerset H, et al. Proximal tubules from caspase-1-deficient mice are protected against hypoxia-induced membrane injury. Nephrology Dialysis Transplantation. 2007;22(4):1052–1061.
    1. Parikh CR, Jani A, Melnikov VY, Faubel S, Edelstein CL. Urinary interleukin-18 is a marker of human acute tubular necrosis. American Journal of Kidney Diseases. 2004;43(3):405–414.
    1. 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. Journal of the American Society of Nephrology. 2005;16(10):3046–3052.
    1. Siew ED, Ikizler TA, Gebretsadik T, et al. Elevated urinary IL-18 levels at the time of ICU admission predict adverse clinical outcomes. Clinical Journal of the American Society of Nephrology. 2010;5(8):1497–1505.
    1. Parikh CR, Coca SG, Thiessen-Philbrook H, et al. Postoperative biomarkers predict acute kidney injury and poor outcomes after adult cardiac surgery. Journal of the American Society of Nephrology. 2011;22(9):p. 1748.
    1. Ichimura T, Bonventre JV, Bailly V, et al. Kidney injury molecule-1 (KIM-1), a putative epithelial cell adhesion molecule containing a novel immunoglobulin domain, is up-regulated in renal cells after injury. Journal of Biological Chemistry. 1998;273(7):4135–4142.
    1. 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. American Journal of Physiology—Renal Physiology. 2006;290(2):F517–F529.
    1. Vaidya VS, Ford GM, Waikar SS, et al. A rapid urine test for early detection of kidney injury. Kidney International. 2009;76(1):108–114.
    1. Han WK, Bailly V, Abichandani R, Thadhani R, Bonventre JV. Kidney Injury Molecule-1 (KIM-1): a novel biomarker for human renal proximal tubule injury. Kidney International. 2002;62(1):237–244.
    1. Westhuyzen J. Cystatin C: a promising marker and predictor of impaired renal function. Annals of Clinical and Laboratory Science. 2006;36(4):387–394.
    1. Herget-Rosenthal S, Marggraf G, Hüsing J, et al. Early detection of acute renal failure by serum cystatin C. Kidney International. 2004;66(3):1115–1122.
    1. Uchida K, Gotoh A. Measurement of cystatin-C and creatinine in urine. Clinica Chimica Acta. 2002;323(1-2):121–128.
    1. Conti M, Moutereau S, Zater M, et al. Urinary cystatin C as a specific marker of tubular dysfunction. Clinical Chemistry and Laboratory Medicine. 2006;44(3):288–291.
    1. Rudnick MR, Kesselheim A, Goldfarb S. Contrast-induced nephropathy: how it develops, how to prevent it. Cleveland Clinic Journal of Medicine. 2006;73(1):75–87.
    1. McCullough P. Outcomes of contrast-induced nephropathy: experience in patients undergoing cardiovascular intervention. Catheterization and Cardiovascular Interventions. 2006;67(3):335–343.
    1. Shaker OG, El-Shehaby A, El-Khatib M. Early diagnostic markers for contrast nephropathy in patients undergoing coronary angiography. Angiology. 2010;61(8):731–736.
    1. Yao X, Panichpisal K, Kurtzman N, Nugent K. Cisplatin nephrotoxicity: a review. American Journal of the Medical Sciences. 2007;334(2):115–124.
    1. Gautier JC, Riefke B, Walter J, et al. Evaluation of novel biomarkers of nephrotoxicity in two strains of rat treated with cisplatin. Toxicologic Pathology. 2010;38(6):943–956.
    1. Vaidya VS, Ozer JS, Dieterle F, et al. Kidney injury molecule-1 outperforms traditional biomarkers of kidney injury in preclinical biomarker qualification studies. Nature Biotechnology. 2010;28(5):478–485.
    1. Prozialeck WC, Edwards JR, Vaidya VS, Bonventre JV. Preclinical evaluation of novel urinary biomarkers of cadmium nephrotoxicity. Toxicology and Applied Pharmacology. 2009;238(3):301–305.
    1. Trevisan A, Chiusolo A, Defazio R, et al. Kidney injury molecule-1 expression in rat proximal tubule after treatment with segment-specific nephrotoxicants: a tool for early screening of potential kidney toxicity. Toxicologic Pathology. 2010;38(3):338–345.
    1. Tonomura Y, Tsuchiya N, Torii M, Uehara T. Evaluation of the usefulness of urinary biomarkers for nephrotoxicity in rats. Toxicology. 2010;273(1–3):53–59.
    1. Dieterle F, Perentes E, Cordier A, et al. Urinary clusterin, cystatin C, beta2-microglobulin and total protein as markers to detect drug-induced kidney injury. Nature Biotechnology. 2010;28(5):463–469.
    1. Jaafar A, Séronie-Vivien S, Malard L, Massip P, Chatelut E, Tack I. Urinary cystatin C can improve the renal safety follow-up of tenofovir-treated patients. AIDS. 2009;23(2):257–259.
    1. Fiehn O. Metabolomics—the link between genotypes and phenotypes. Plant Molecular Biology. 2002;48(1-2):155–171.
    1. Portilla D, Schnackenberg L, Beger RD. Metabolomics as an extension of proteomic analysis: study of acute kidney injury. Seminars in Nephrology. 2007;27(6):609–620.
    1. Chapman JR, O’Connell PJ, Nankivell BJ. Chronic renal allograft dysfunction. Journal of the American Society of Nephrology. 2005;16(10):3015–3026.
    1. Lenz EM, Bright J, Knight R, Wilson ID, Major H. Cyclosporin A-induced changes in endogenous metabolites in rat urine: a metabonomic investigation using high field 1H NMR spectroscopy, HPLC-TOF/MS and chemometrics. Journal of Pharmaceutical and Biomedical Analysis. 2004;35(3):599–608.
    1. Christians U, Schmitz V, Schöning W, et al. Toxicodynamic therapeutic drug monitoring of immunosuppressants: promises, reality, and challenges. Therapeutic Drug Monitoring. 2008;30(2):151–158.
    1. Klawitter J, Klawitter J, Kushner E, et al. Association of immunosuppressant-induced protein changes in the rat kidney with changes in urine metabolite patterns: a proteo-metabonomic study. Journal of Proteome Research. 2010;9(2):865–875.
    1. Klawitter J, Bendrick-Peart J, Rudolph B, et al. Urine metabolites reflect time-dependent effects of cyclosporine and sirolimus on rat kidney function. Chemical Research in Toxicology. 2009;22(1):118–128.
    1. Le Moyec L, Pruna A, Eugene M, et al. Proton nuclear magnetic resonance spectroscopy of urine and plasma in renal transplantation follow-up. Nephron. 1993;65(3):433–439.
    1. Foxall PJD, Mellotte GJ, Bending MR, Lindon JC, Nicholson JK. NMR spectroscopy as a novel approach to the monitoring of renal transplant function. Kidney International. 1993;43(1):234–245.
    1. Wang JN, Zhou Y, Zhu TY, Wang X, Guo YL. Prediction of acute cellular renal allograft rejection by urinary metabolomics using MALDI-FTMS. Journal of Proteome Research. 2008;7(8):3597–3601.
    1. Klawitter J, Haschke M, Kahle C, Dingmann C, Leibfritz D, Christians U. Toxicodynamic effects of ciclosporin are reflected by metabolite profiles in the urine of healthy individuals after a single dose. British Journal of Clinical Pharmacology. 2010;70:241–251.
    1. Stapenhorst L, Sassen R, Beck B, Laube N, Hesse A, Hoppe B. Hypocitraturia as a risk factor for nephrocalcinosis after kidney transplantation. Pediatric Nephrology. 2005;20(5):652–656.
    1. Hunter A, Campbell WR. The probable accuracy, in whole blood and plasma, of colorimetric determinations of creatinine and creatine. Journal of Biological Chemistry. 1917;32:p. 195.

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