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Table of Contents
Vol. 28, No. 3, 2009
Issue release date: October 2009
Section title: In-Depth Review
Free Access
Blood Purif 2009;28:165–174
(DOI:10.1159/000227785)

Early Diagnosis of Acute Kidney Injury: The Promise of Novel Biomarkers

Soni S.S.a, b, e · Ronco C.a, c · Katz N.d · Cruz D.N.a, c
aSan Bortolo Hospital, Vicenza, Italy; bMediciti Hospitals, Hyderabad, India; cInternational Renal Research Institute, Vicenza, Italy; dDepartment of Surgery, George Washington University, Washington, D.C., USA; e Seth Nandlal Dhoot Hospital, Aurangabad, India
email Corresponding Author

Dr. Dinna N. Cruz

Nephrology Dialysis and Transplantation, San Bortolo Hospital

Via Rodolfi, 37, IT–36100 Vicenza (Italy)

Tel. +39 0444 753 650, Fax +39 0444 753 949

E-Mail dinnacruzmd@yahoo.com


References

  1. Smith H: The Kidney: Structure and Function in Health and Disease. London, Oxford University Press, 1964.
  2. Lameire N, Van Biesen W, Vanholder R: Acute renal failure. Lancet 2005;365:417–430.
  3. Kellum JA, Levin N, Bouman C, Lameire N: Developing a consensus classification system for acute renal failure. Curr Opin Crit Care 2002;8:509–514.
  4. Bellomo R, Kellum J, Ronco C: Acute renal failure: time for consensus. Intensive Care Med 2001;27:1685–1688.
  5. Bellomo R Ronco C, Kellum JA, the ADQI Workgroup: 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.
  6. Hoste EA, Clermont G, Kersten A, Venkataraman R, Angus DC, De Bacquer D, Kellum JA: Rifle criteria for acute kidney injury are associated with hospital mortality in critically ill patients: a cohort analysis. Crit Care 2006;10:R73.
  7. Hoste EA, Kellum JA: Rifle criteria provide robust assessment of kidney dysfunction and correlate with hospital mortality. Crit Care Med 2006;34:2016–2017.
  8. Cruz DN, Bolgan I, Perazella MA, Bonello M, de Cal M, Corradi V, Polanco N, Ocampo C, Nalesso F, Piccinni P, Ronco C: North-East Italian Prospective Hospital Renal Outcome Survey on Acute Kidney Injury (NEIPHROS-AKI): targeting the problem with the rifle criteria. Clin J Am Soc Nephrol 2007;2:418–425.
  9. 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.
  10. Lopes JA, Fernandes P, Jorge S, Goncalves S, Alvarez A, Costa e Silva Z, Franca C, Prata MM: Acute kidney injury in intensive care unit patients: a comparison between the RIFLE and the Acute Kidney Injury Network classifications. Crit Care 2008;12:R110.
  11. Bagshaw SM, George C, Bellomo R: A comparison of the RIFLE and AKIN criteria for acute kidney injury in critically ill patients. Nephrol Dial Transplant 2008;23:1569–1574.
  12. Devarajan P: Emerging biomarkers of acute kidney injury. Contrib Nephrol. Basel, Karger, 2007, vol 156, pp 203–212.
  13. Feest TG, Round A, Hamad S: Incidence of severe acute renal failure in adults: results of a community-based study. BMJ 1993;306:481–483.
  14. Hsu CY, McCulloch CE, Fan D, Ordonez JD, Chertow GM, Go AS: Community-based incidence of acute renal failure. Kidney Int 2007;72:208–212.
  15. Metnitz PG, Krenn CG, Steltzer H, Lang T, Ploder J, Lenz K, Le Gall JR, Druml W: Effect of acute renal failure requiring renal replacement therapy on outcome in critically ill patients. Crit Care Med 2002;30:2051–2058.
  16. Schrier RW, Wang W: Acute renal failure and sepsis. N Engl J Med 2004;351:159–169.
  17. Uchino S, Kellum JA, Bellomo R, Doig GS, Morimatsu H, Morgera S, Schetz M, Tan I, Bouman C, Macedo E, Gibney N, Tolwani A, Ronco C: Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA 2005;294:813–818.
  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.
  19. Blantz RC: Pathophysiology of pre-renal azotemia. Kidney Int 1998;53:512–523.
  20. Nash K, Hafeez A, Hou S: Hospital-acquired renal insufficiency. Am J Kidney Dis 2002;39:930–936.
  21. Cerda J, Lameire N, Eggers P, Pannu N, Uchino S, Wang H, Bagga A, Levin A: Epidemiology of acute kidney injury. Clin J Am Soc Nephrol 2008;3:881–886.
  22. Barsoum RS: Tropical acute renal failure. Contrib Nephrol. Basel, Karger, 2004, vol 144, pp 44–52.
  23. Devarajan P: Update on mechanisms of ischemic acute kidney injury. J Am Soc Nephrol 2006;17:1503–1520.
  24. Wan L, Bagshaw SM, Langenberg C, Saotome T, May C, Bellomo R: Pathophysiology of septic acute kidney injury: What do we really know? Crit Care Med 2008;36:S198–S203.
  25. Safirstein RL: Acute renal failure: from renal physiology to the renal transcriptome. Kidney Int Suppl 2004;S62–S66.

    External Resources

  26. Kuitunen A, Vento A, Suojaranta-Ylinen R, Pettila V: Acute renal failure after cardiac surgery: evaluation of the RIFLE Classification. Ann Thorac Surg 2006;81:542–546.
  27. Dasta JF, Kane-Gill SL, Durtschi AJ, Pathak DS, Kellum JA: Costs and outcomes of acute kidney injury following cardiac surgery. Nephrol Dial Transplant 2008;23:1970–1974.
  28. Star RA: Treatment of acute renal failure. Kidney Int 1998;54:1817–1831.
  29. Ympa YP, Sakr Y, Reinhart K, Vincent JL: Has mortality from acute renal failure decreased? A systematic review of the literature. Am J Med 2005;118:827–832.
  30. Bagshaw SM, George C, Dinu I, Bellomo R: A multi-centre evaluation of the RIFLE criteria for early acute kidney injury in critically ill patients. Nephrol Dial Transplant 2008;23:1203–1210.
  31. Ricci Z, Cruz D, Ronco C: The RIFLE criteria and mortality in acute kidney injury: a systematic review. Kidney Int 2008;73:538–546.
  32. Bagshaw SM, Mortis G, Doig CJ, Godinez-Luna T, Fick GH, Laupland KB: One-year mortality in critically ill patients by severity of kidney dysfunction: a population-based assessment. Am J Kidney Dis 2006;48:402–409.
  33. Bhandari S, Turney JH: Survivors of acute renal failure who do not recover renal function. QJM 1996;89:415–421.
  34. Shaw NJ, Brocklebank JT, Dickinson DF, Wilson N, Walker DR: Long-term outcome for children with acute renal failure following cardiac surgery. Int J Cardiol 1991;31:161–165.
  35. Himmelfarb J, Ikizler TA: Acute kidney injury: changing lexicography, definitions, and epidemiology. Kidney Int 2007;71:971–976.
  36. Bellomo R, Kellum JA, Ronco C: Defining acute renal failure: physiological principles. Intensive Care Med 2004;30:33–37.
  37. Coca SG, Parikh CR: Urinary biomarkers for acute kidney injury: perspectives on translation. Clin J Am Soc Nephrol 2008;3:481–490.
  38. Devarajan P: Neutrophil gelatinase-associated lipocalin (NGAL): a new marker of kidney disease. Scand J Clin Lab Invest Suppl 2008;241:89–94.
  39. Schrier RW: Need to intervene in established acute renal failure. J Am Soc Nephrol 2004;15:2756–2758.
  40. Ronco C: NGAL: an emerging biomarker of acute kidney injury. Int J Artif Organs 2008;31:199–200.
  41. Vaidya VS, Ferguson MA, Bonventre JV: Biomarkers of acute kidney injury. Annu Rev Pharmacol Toxicol 2008;48:463–493.
  42. Nguyen MT, Devarajan P: Biomarkers for the early detection of acute kidney injury. Pediatr Nephrol 2008;23:2151–2157.
  43. Herget-Rosenthal S, Marggraf G, Husing J, Goring 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.
  44. Villa P, Jimenez M, Soriano MC, Manzanares J, Casasnovas P: Serum cystatin C concentration as a marker of acute renal dysfunction in critically ill patients. Crit Care 2005;9:R139–R143.
  45. Delanaye P, Lambermont B, Chapelle JP, Gielen J, Gerard P, Rorive G: Plasmatic cystatin C for the estimation of glomerular filtration rate in intensive care units. Intensive Care Med 2004;30:980–983.
  46. Koyner JL, Bennett MR, Worcester EM, Ma Q, Raman J, Jeevanandam V, Kasza KE, O’Connor MF, Konczal DJ, Trevino S, Devarajan P, Murray PT: Urinary cystatin C as an early biomarker of acute kidney injury following adult cardiothoracic surgery. Kidney Int 2008;74:1059–1069.
  47. 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.
  48. 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.
  49. Parikh CR, Devarajan P: New biomarkers of acute kidney injury. Crit Care Med 2008;36:S159–S165.
  50. 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. Crit Care 2008;12:R96.
  51. Ichimura T, Bonventre JV, Bailly V, Wei H, Hession CA, Cate RL, Sanicola M: Kidney injury molecule-1 (KIM-1), a putative epithelial cell adhesion molecule containing a novel immunoglobulin domain, is upregulated in renal cells after injury. J Biol Chem 1998;273:4135–4142.
  52. Ichimura T, Hung CC, Yang SA, Stevens JL, Bonventre JV: Kidney injury molecule-1: a tissue and urinary biomarker for nephrotoxicant-induced renal injury. Am J Physiol Renal Physiol 2004;286:F552–F563.
  53. 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 Int 2002;62:237–244.
  54. 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.
  55. Liangos O, Perianayagam MC, Vaidya VS, Han WK, Wald R, Tighiouart H, MacKinnon RW, Li L, Balakrishnan VS, Pereira BJ, Bonventre JV, Jaber BL: Urinary N-acetyl-β-(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.
  56. Ronco C: N-GAL: Diagnosing AKI as soon as possible. Crit Care 2007;11:173.
  57. Flower DR, North AC, Sansom CE: The lipocalin protein family: structural and sequence overview. Biochim Biophys Acta 2000;1482:9–24.
  58. Uttenthal O: NGAL: a marker molecule for the distressed kidney? Clin Lab Internat 2005;29:39–41.
  59. Cowland JB, Borregaard N: Molecular characterization and pattern of tissue expression of the gene for neutrophil gelatinase-associated lipocalin from humans. Genomics 1997;45:17–23.
  60. Schmidt-Ott KM, Mori K, Kalandadze A, Li JY, Paragas N, Nicholas T, Devarajan P, Barasch J: Neutrophil gelatinase-associated lipocalin-mediated iron traffic in kidney epithelia. Curr Opin Nephrol Hypertens 2006;15:442–449.
  61. 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.
  62. 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.
  63. Mori K, Lee HT, Rapoport D, Drexler IR, Foster K, Yang J, Schmidt-Ott KM, Chen X, Li JY, Weiss S, Mishra J, Cheema FH, Markowitz G, Suganami T, Sawai K, Mukoyama M, Kunis C, D’Agati V, Devarajan P, Barasch J: Endocytic delivery of lipocalin-siderophore-iron complex rescues the kidney from ischemia-reperfusion injury. J Clin Invest 2005;115:610–621.
  64. Devarajan R: Novel biomarkers for the early prediction of acute kidney injury. Cancer Ther 2005;3:477–488.
  65. Mishra J, Dent C, Tarabishi R, Mitsnefes MM, Ma Q, Kelly C, Ruff SM, Zahedi K, Shao M, Bean J, Mori K, Barasch J, Devarajan P: Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery. Lancet 2005;365:1231–1238.
  66. Hirsch R, Dent C, Pfriem H, Allen J, Beekman RH 3rd, Ma Q, Dastrala S, Bennett M, Mitsnefes M, Devarajan P: NGAL is an early predictive biomarker of contrast-induced nephropathy in children. Pediatr Nephrol 2007;22:2089–2095.
  67. Wheeler DS, Devarajan P, Ma Q, Harmon K, Monaco M, Cvijanovich N, Wong HR: Serum neutrophil gelatinase-associated lipocalin (NGAL) as a marker of acute kidney injury in critically ill children with septic shock. Crit Care Med 2008;36:1297–1303.
  68. Zappitelli M, Washburn KK, Arikan AA, Loftis L, Ma Q, Devarajan P, Parikh CR, Goldstein SL: Urine neutrophil gelatinase-associated lipocalin is an early marker of acute kidney injury in critically ill children: a prospective cohort study. Crit Care 2007;11:R84.
  69. Nickolas TL, O’Rourke MJ, Yang J, Sise ME, Canetta PA, Barasch N, Buchen C, Khan F, Mori K, Giglio J, Devarajan P, Barasch J: Sensitivity and specificity of a single emergency department measurement of urinary neutrophil gelatinase-associated lipocalin for diagnosing acute kidney injury. Ann Intern Med 2008;148:810–819.
  70. Makris K, Markou N, Evodia E, Dimopoulou E, Drakopoulos I, Ntetsika K, Rizos D, Baltopoulos G, Haliassos A: Urinary neutrophil gelatinase-associated lipocalin (NGAL) as an early marker of acute kidney injury in critically ill multiple trauma patients. Clin Chem Lab Med 2009;47:79–82.
  71. Dent CL, Ma Q, Dastrala S, Bennett M, Mitsnefes MM, Barasch J, Devarajan P: Plasma neutrophil gelatinase-associated lipocalin predicts acute kidney injury, morbidity and mortality after pediatric cardiac surgery: a prospective uncontrolled cohort study. Crit Care 2007;11:R127.
  72. Bachorzewska-Gajewska H, Malyszko J, Sitniewska E, Malyszko JS, Dobrzycki S: Neutrophil gelatinase-associated lipocalin (NGAL) correlations with cystatin C, serum creatinine and EGFR in patients with normal serum creatinine undergoing coronary angiography. Nephrol Dial Transplant 2007;22:295–296.
  73. Wagener G, Jan M, Kim M, Mori K, Barasch JM, Sladen RN, Lee HT: Association between increases in urinary neutrophil gelatinase-associated lipocalin and acute renal dysfunction after adult cardiac surgery. Anesthesiology 2006;105:485–491.
  74. 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.
  75. Tuladhar SM, Puntmann VO, Soni M, Punjabi PP, Bogle RG: Rapid detection of acute kidney injury by plasma and urinary neutrophil gelatinase-associated lipocalin after cardiopulmonary bypass. J Cardiovasc Pharmacol 2009;53:261–266.
  76. Bachorzewska-Gajewska H, Malyszko J, Sitniewska E, Malyszko JS, Pawlak K, Mysliwiec M, Lawnicki S, Szmitkowski M, Dobrzycki S: Could neutrophil-gelatinase-associated lipocalin and cystatin C predict the development of contrast-induced nephropathy after percutaneous coronary interventions in patients with stable angina and normal serum creatinine values? Kidney Blood Press Res 2007;30:408–415.
  77. Wagener G, Gubitosa G, Wang S, Borregaard N, Kim M, Lee HT: Urinary neutrophil gelatinase-associated lipocalin and acute kidney injury after cardiac surgery. Am J Kidney Dis 2008;52:425–433.
  78. Fischer UM, Weissenberger WK, Warters RD, Geissler HJ, Allen SJ, Mehlhorn U: Impact of cardiopulmonary bypass management on postcardiac surgery renal function. Perfusion 2002;17:401–406.
  79. Bennett M, Dent CL, Ma Q, Dastrala S, Grenier F, Workman R, Syed H, Ali S, Barasch J, Devarajan P: Urine NGAL predicts severity of acute kidney injury after cardiac surgery: a prospective study. Clin J Am Soc Nephrol 2008;3:665–673.
  80. Trachtman H, Christen E, Cnaan A, Patrick J, Mai V, Mishra J, Jain A, Bullington N, Devarajan P: Urinary neutrophil gelatinase-associated lipocalcin in D+HUS: a novel marker of renal injury. Pediatr Nephrol 2006;21:989–994.
  81. Mishra J, Mori K, Ma Q, Kelly C, Yang J, Mitsnefes M, Barasch J, Devarajan P: Amelioration of ischemic acute renal injury by neutrophil gelatinase-associated lipocalin. J Am Soc Nephrol 2004;15:3073–3082.
  82. Bagshaw SM, Bellomo R, Kellum JA: Oliguria, volume overload, and loop diuretics. Crit Care Med 2008;36:S172–S178.
  83. Arnaoutakis GJ, Bihorac A, Martin TD, Hess PJ Jr, Klodell CT, Ejaz AA, Garvan C, Tribble CG, Beaver TM: RIFLE criteria for acute kidney injury in aortic arch surgery. J Thorac Cardiovasc Surg 2007;134:1554–1561.
  84. Parikh CR, Jani A, Mishra J, Ma Q, Kelly C, Barasch J, Edelstein CL, Devarajan P: Urine NGAL and IL-18 are predictive biomarkers for delayed graft function following kidney transplantation. Am J Transplant 2006;6:1639–1645.
  85. Brunner HI, Mueller M, Rutherford C, Passo MH, Witte D, Grom A, Mishra J, Devarajan P: Urinary neutrophil gelatinase-associated lipocalin as a biomarker of nephritis in childhood-onset systemic lupus erythematosus. Arthritis Rheum 2006;54:2577–2584.
  86. Suzuki M, Wiers KM, Klein-Gitelman MS, Haines KA, Olson J, Onel KB, O’Neil K, Passo MH, Singer NG, Tucker L, Ying J, Devarajan P, Brunner HI: Neutrophil gelatinase-associated lipocalin as a biomarker of disease activity in pediatric lupus nephritis. Pediatr Nephrol 2008;23:403–412.
  87. Ding H, He Y, Li K, Yang J, Li X, Lu R, Gao W: Urinary neutrophil gelatinase-associated lipocalin (NGAL) is an early biomarker for renal tubulointerstitial injury in IgA nephropathy. Clin Immunol 2007;123:227–234.
  88. Bolignano D, Coppolino G, Campo S, Aloisi C, Nicocia G, Frisina N, Buemi M: Neutrophil gelatinase-associated lipocalin in patients with autosomal-dominant polycystic kidney disease. Am J Nephrol 2007;27:373–378.
  89. Smith ER, Zurakowski D, Saad A, Scott RM, Moses MA: Urinary biomarkers predict brain tumor presence and response to therapy. Clin Cancer Res 2008;14:2378–2386.
  90. Manfredi MA, Zurakowski D, Rufo PA, Walker TR, Fox VL, Moses MA: Increased incidence of urinary matrix metalloproteinases as predictors of disease in pediatric patients with inflammatory bowel disease. Inflamm Bowel Dis 2008;14:1091–1096.
  91. D’Anna R, Baviera G, Giordano D, Todarello G, Corrado F, Buemi M: Second trimester neutrophil gelatinase-associated lipocalin as a potential prediagnostic marker of preeclampsia. Acta Obstet Gynecol Scand 2008;87:1370–1373.
  92. Bobek I, de Cal M, Cruz D, Nalesso F, Lentini P, Corradi V, Happio M, Ronco C: In vitro removal of NGAL by extracorporeal therapy. J Am Soc Nephrol 2008;19:457A.
  93. Devarajan P: Neutrophil gelatinase-associated lipocalin – an emerging troponin for kidney injury. Nephrol Dial Transplant 2008;23:3737–3743.