International Urology and Nephrology

, Volume 46, Issue 1, pp 1–7

Current developments in early diagnosis of acute kidney injury

  • Nicholas Obermüller
  • Helmut Geiger
  • Christine Weipert
  • Anja Urbschat
Nephrology - Review


Acute kidney injury (AKI) is a very frequent and serious clinical problem, accounting for overall high morbidity and mortality. Up to date, mortality due to AKI is virtually unchanged over the past 50 years. This may partly be explained due to a delay in initiating renal protective and appropriate therapeutic measures since until now there are no reliable early-detecting biomarkers. The gold standard, serum creatinine, displays poor specificity and sensitivity with regard to identification of the incipient phase of AKI, and this is also true for cystatin C. We aimed to review novel biomarkers of AKI in urine and serum which have now progressed to the clinical phase. The main focus refers to their diagnostic and prognostic value. For this purpose, a web-based literature search using PubMed was performed comprising the following terms: renal failure, acute kidney injury and biomarkers. New molecules such as neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), N-acetyl-β-d-glucosaminidase (NAG), monocyte chemotactic peptide (MCP-1), Il-18, liver-type fatty acid-binding protein (L-FABP) and Netrin-1 are available and represent promising new markers that, however, need to be further evaluated in the clinical setting for suitability. In clinical settings with incipient AKI, not only the development and the implementation of more sensitive, practicable and accurate biomarkers are required for well-timed treatment initiation. Just as important is a substantial improvement of refined and applicable prophylactic therapeutic options in these situations. Before full adoption in clinical practice can be accomplished, adequately powered clinical trials testing a row of biomarkers are strongly warranted.


Acute kidney injury Acute renal failure Biomarker NGAL KIM-1 


  1. 1.
    Brar H, Olivier J, Lebrun C et al (2008) Predictors of mortality in a cohort of intensive care unit patients with acute renal failure receiving continuous renal replacement therapy. Am J Med Sci 335:342–347PubMedCrossRefGoogle Scholar
  2. 2.
    Ympa YP, Sakr Y, Reinhart K et al (2005) Has mortality from acute renal failure decreased? A systematic review of the literature. Am J Med 118:827–832PubMedCrossRefGoogle Scholar
  3. 3.
    Nguyen MT, Devarajan P (2008) Biomarkers for the early detection of acute kidney injury. Pediatr Nephrol 23:2151–2157PubMedCrossRefGoogle Scholar
  4. 4.
    Ferguson MA, Vaidya VS, Waikar SS et al (2010) Urinary liver-type fatty acid-binding protein predicts adverse outcomes in acute kidney injury. Kidney Int 77:708–714PubMedCentralPubMedCrossRefGoogle Scholar
  5. 5.
    Bellomo R, Ronco C, Kellum JA et al (2004) 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 8:R204–R212PubMedCrossRefGoogle Scholar
  6. 6.
    Mehta R, Kellum J, Shah S et al (2007) Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury. Crit Care 11:R31PubMedCrossRefGoogle Scholar
  7. 7.
    Nash K, Hafeez A, Hou S (2002) Hospital-acquired renal insufficiency. Am J Kidney Dis 39:930–936PubMedCrossRefGoogle Scholar
  8. 8.
    Bonventre JV (2010) Pathophysiology of AKI: injury and normal and abnormal repair. Contrib Nephrol 165:9–17PubMedCrossRefGoogle Scholar
  9. 9.
    Humphreys BD, Bonventre JV (2008) Mesenchymal stem cells in acute kidney injury. Annu Rev Med 59:311–325PubMedCrossRefGoogle Scholar
  10. 10.
    Chertow GM, Burdick E, Honour M et al (2005) Acute kidney injury, mortality, length of stay, and costs in hospitalized patients. J Am Soc Nephrol 16:3365–3370PubMedCrossRefGoogle Scholar
  11. 11.
    Ozer JS, Dieterle F, Troth S et al (2010) A panel of urinary biomarkers to monitor reversibility of renal injury and a serum marker with improved potential to assess renal function. Nat Biotechnol 28:486–494PubMedCrossRefGoogle Scholar
  12. 12.
    Bonventre JV (2008) Kidney Injury Molecule-1 (KIM-1): a specific and sensitive biomarker of kidney injury. Scand J Clin Lab Invest Suppl 241:78–83PubMedCrossRefGoogle Scholar
  13. 13.
    Mishra J, Ma Q, Prada A et al (2003) Identification of neutrophil gelatinase-associated lipocalin as a novel early urinary biomarker for ischemic renal injury. J Am Soc Nephrol 14:2534–2543PubMedCrossRefGoogle Scholar
  14. 14.
    Munshi R, Johnson A, Siew ED et al (2011) MCP-1 gene activation marks acute kidney injury. J Am Soc Nephrol 22:165–175PubMedCrossRefGoogle Scholar
  15. 15.
    Kamijo A, Sugaya T, Hikawa A et al (2006) Urinary liver-type fatty acid binding protein as a useful biomarker in chronic kidney disease. Mol Cell Biochem 284:175–182PubMedCrossRefGoogle Scholar
  16. 16.
    Matsui K, Kamijo-Ikemori A, Hara M et al (2011) Clinical significance of tubular and podocyte biomarkers in acute kidney injury. Clin Exp Nephrol 15:220–225PubMedCrossRefGoogle Scholar
  17. 17.
    Flower DR, North AC, Sansom CE (2000) The lipocalin protein family: structural and sequence overview. Biochim Biophys Acta 1482:9–24PubMedCrossRefGoogle Scholar
  18. 18.
    Supavekin S, Zhang W, Kucherlapati R et al (2003) Differential gene expression following early renal ischemia/reperfusion. Kidney Int 63:1714–1724PubMedCrossRefGoogle Scholar
  19. 19.
    Haase M, Bellomo R, Devarajan P et al (2009) 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 54:1012–1024PubMedCrossRefGoogle Scholar
  20. 20.
    Soni SS, Cruz D, Bobek I et al (2010) NGAL: a biomarker of acute kidney injury and other systemic conditions. Int Urol Nephrol 42:141–150PubMedCrossRefGoogle Scholar
  21. 21.
    Kiani AN, Wu T, Fang H et al (2012) Urinary vascular cell adhesion molecule, but not neutrophil gelatinase-associated lipocalin, is associated with lupus nephritis. J Rheumatol 39:1231–1237PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.
    Ichimura T, Bonventre JV, Bailly V et al (1998) 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. J Biol Chem 273:4135–4142PubMedCrossRefGoogle Scholar
  23. 23.
    Han WK, Bailly V, Abichandani R et al (2002) Kidney Injury Molecule-1 (KIM-1): a novel biomarker for human renal proximal tubule injury. Kidney Int 62:237–244PubMedCrossRefGoogle Scholar
  24. 24.
    Liangos O, Perianayagam MC, Vaidya VS et al (2007) Urinary N-acetyl-beta-(D)-glucosaminidase activity and kidney injury of urinary liver-type fatty acid-bindingmolecule-1 level are associated with adverse outcomes in acute renal failure. J Am Soc Nephrol 18:904–912PubMedCrossRefGoogle Scholar
  25. 25.
    Nejat M, Pickering JW, Devarajan P et al (2012) Some biomarkers of acute kidney injury are increased in pre-renal acute injury. Kidney Int 81:1254–1262PubMedCentralPubMedCrossRefGoogle Scholar
  26. 26.
    Luo Q, Zhou F, Dong H et al (2013) Implication of combined urinary biomarkers in early diagnosis of acute kidney injury following percutaneous coronary intervention. Clin Nephrol 79:85–92PubMedCrossRefGoogle Scholar
  27. 27.
    Bonventre JV (2009) Kidney injury molecule-1 (KIM-1): a urinary biomarker and much more. Nephrol Dial Transplant 24:3265–3268PubMedCrossRefGoogle Scholar
  28. 28.
    Bernard AM, Vyskocil AA, Mahieu P et al (1987) Assessment of urinary retinol-binding protein as an index of proximal tubular injury. Clin Chem 33:775–779PubMedGoogle Scholar
  29. 29.
    Price RG (1992) The role of NAG (N-acetyl-beta-d-glucosaminidase) in the diagnosis of kidney disease including the monitoring of nephrotoxicity. Clin Nephrol 38(Suppl 1):S14–S19PubMedGoogle Scholar
  30. 30.
    Marchewka Z, Kuzniar J, Dlugosz A (2001) Enzymuria and beta2-mikroglobulinuria in the assessment of the influence of proteinuria on the progression of glomerulopathies. Int Urol Nephrol 33:673–676PubMedCrossRefGoogle Scholar
  31. 31.
    Katagiri D, Doi K, Honda K (2012) Combination of two urinary biomarkers predicts acute kidney injury after adult cardiac surgery. Ann Thorac Surg 93:577–583PubMedCrossRefGoogle Scholar
  32. 32.
    Rice JC, Spence JS, Yetman DL et al (2002) Monocyte chemoattractant protein-1 expression correlates with monocyte infiltration in the post-ischemic kidney. Ren Fail 24:703–723PubMedCrossRefGoogle Scholar
  33. 33.
    Gauer S, Sichler O, Obermuller N et al (2007) IL-18 is expressed in the intercalated cell of human kidney. Kidney Int 72:1081–1087PubMedCrossRefGoogle Scholar
  34. 34.
    Parikh CR, Jani A, Melnikov VY et al (2004) Urinary interleukin-18 is a marker of human acute tubular necrosis. Am J Kidney Dis 43:405–414PubMedCrossRefGoogle Scholar
  35. 35.
    Manabe K, Kamihata H, Motohiro M et al (2012) Urinary liver-type fatty acid-binding protein level as a predictive biomarker of contrast-induced acute kidney injury. Eur J Clin Invest 42:557–563PubMedCrossRefGoogle Scholar
  36. 36.
    Przybylowski P, Koc-Zorawska E, Malyszko JS et al (2011) Liver fatty-acid-binding protein in heart and kidney allograft recipients in relation to kidney function. Transplant Proc 43:3064–3067PubMedCrossRefGoogle Scholar
  37. 37.
    Matsui K, Kamijo-Ikemori A, Sugaya T et al (2012) Usefulness of urinary biomarkers in early detection of acute kidney injury after cardiac surgery in adults. Circ J 76:213–220PubMedCrossRefGoogle Scholar
  38. 38.
    Portilla D, Dent C, Sugaya T et al (2008) Liver fatty acid-binding protein as a biomarker of acute kidney injury after cardiac surgery. Kidney Int 73:465–472PubMedCrossRefGoogle Scholar
  39. 39.
    Susantitaphong P, Siribamrungwong M, Doi K (2013) Performance of urinary liver-typy acid-binding protein in acute kidney injury: a meta-analysis. Am J Kidney Dis 61:430–439PubMedCrossRefGoogle Scholar
  40. 40.
    Reeves WB, Kwon O, Ramesh G (2008) Netrin-1 and kidney injury. II. Netrin-1 is an early biomarker of acute kidney injury. Am J Physiol Renal Physiol 294:F731–F738PubMedCrossRefGoogle Scholar
  41. 41.
    Ramesh G, Krawczeski CD, Woo JG et al (2010) Urinary netrin-1 is an early predictive biomarker of acute kidney injury after cardiac surgery. Clin J Am Soc Nephrol 5:395–401PubMedCrossRefGoogle Scholar
  42. 42.
    Ramesh G, Kwon O, Ahn K (2010) Netrin-1: a novel universal biomarker of human kidney injury. Transplant Proc 42:1519–1522PubMedCrossRefGoogle Scholar
  43. 43.
    Kashani K, Al-Khafaji A, Ardiles T et al (2013) Discovery and validation of cell cycle arrest biomarkers in human acute kidney injury. Crit Care 17:R25PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Nicholas Obermüller
    • 1
  • Helmut Geiger
    • 1
  • Christine Weipert
    • 2
  • Anja Urbschat
    • 3
  1. 1. Division of Nephrology, III Medical ClinicGoethe-University Hospital Frankfurt am MainFrankfurtGermany
  2. 2.Division of Urology and AndrologyLandeskrankenhaus Hall in Tirol Hall in TirolAustria
  3. 3.Division of Urology and Pediatric UrologyGoethe-University Hospital Frankfurt am MainFrankfurtGermany

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