Skip to main content
Top
Published in: International Urology and Nephrology 1/2014

01-01-2014 | Nephrology - Review

Current developments in early diagnosis of acute kidney injury

Authors: Nicholas Obermüller, Helmut Geiger, Christine Weipert, Anja Urbschat

Published in: International Urology and Nephrology | Issue 1/2014

Login to get access

Abstract

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.
Literature
1.
go back to reference 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 335:342–347PubMedCrossRef 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 335:342–347PubMedCrossRef
2.
go back to reference 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 118:827–832PubMedCrossRef 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 118:827–832PubMedCrossRef
3.
go back to reference Nguyen MT, Devarajan P (2008) Biomarkers for the early detection of acute kidney injury. Pediatr Nephrol 23:2151–2157PubMedCrossRef Nguyen MT, Devarajan P (2008) Biomarkers for the early detection of acute kidney injury. Pediatr Nephrol 23:2151–2157PubMedCrossRef
4.
go back to reference 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 77:708–714PubMedCentralPubMedCrossRef 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 77:708–714PubMedCentralPubMedCrossRef
5.
go back to reference 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–R212PubMedCrossRef 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–R212PubMedCrossRef
6.
go back to reference 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:R31PubMedCrossRef 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:R31PubMedCrossRef
7.
8.
go back to reference Bonventre JV (2010) Pathophysiology of AKI: injury and normal and abnormal repair. Contrib Nephrol 165:9–17PubMedCrossRef Bonventre JV (2010) Pathophysiology of AKI: injury and normal and abnormal repair. Contrib Nephrol 165:9–17PubMedCrossRef
9.
go back to reference Humphreys BD, Bonventre JV (2008) Mesenchymal stem cells in acute kidney injury. Annu Rev Med 59:311–325PubMedCrossRef Humphreys BD, Bonventre JV (2008) Mesenchymal stem cells in acute kidney injury. Annu Rev Med 59:311–325PubMedCrossRef
10.
go back to reference 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 16:3365–3370PubMedCrossRef 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 16:3365–3370PubMedCrossRef
11.
go back to reference 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 28:486–494PubMedCrossRef 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 28:486–494PubMedCrossRef
12.
go back to reference Bonventre JV (2008) Kidney Injury Molecule-1 (KIM-1): a specific and sensitive biomarker of kidney injury. Scand J Clin Lab Invest Suppl 241:78–83PubMedCrossRef Bonventre JV (2008) Kidney Injury Molecule-1 (KIM-1): a specific and sensitive biomarker of kidney injury. Scand J Clin Lab Invest Suppl 241:78–83PubMedCrossRef
13.
go back to reference 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 14:2534–2543PubMedCrossRef 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 14:2534–2543PubMedCrossRef
14.
go back to reference Munshi R, Johnson A, Siew ED et al (2011) MCP-1 gene activation marks acute kidney injury. J Am Soc Nephrol 22:165–175PubMedCrossRef Munshi R, Johnson A, Siew ED et al (2011) MCP-1 gene activation marks acute kidney injury. J Am Soc Nephrol 22:165–175PubMedCrossRef
15.
go back to reference 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 284:175–182PubMedCrossRef 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 284:175–182PubMedCrossRef
16.
go back to reference Matsui K, Kamijo-Ikemori A, Hara M et al (2011) Clinical significance of tubular and podocyte biomarkers in acute kidney injury. Clin Exp Nephrol 15:220–225PubMedCrossRef Matsui K, Kamijo-Ikemori A, Hara M et al (2011) Clinical significance of tubular and podocyte biomarkers in acute kidney injury. Clin Exp Nephrol 15:220–225PubMedCrossRef
17.
go back to reference Flower DR, North AC, Sansom CE (2000) The lipocalin protein family: structural and sequence overview. Biochim Biophys Acta 1482:9–24PubMedCrossRef Flower DR, North AC, Sansom CE (2000) The lipocalin protein family: structural and sequence overview. Biochim Biophys Acta 1482:9–24PubMedCrossRef
18.
go back to reference Supavekin S, Zhang W, Kucherlapati R et al (2003) Differential gene expression following early renal ischemia/reperfusion. Kidney Int 63:1714–1724PubMedCrossRef Supavekin S, Zhang W, Kucherlapati R et al (2003) Differential gene expression following early renal ischemia/reperfusion. Kidney Int 63:1714–1724PubMedCrossRef
19.
go back to reference 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 54:1012–1024PubMedCrossRef 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 54:1012–1024PubMedCrossRef
20.
go back to reference Soni SS, Cruz D, Bobek I et al (2010) NGAL: a biomarker of acute kidney injury and other systemic conditions. Int Urol Nephrol 42:141–150PubMedCrossRef Soni SS, Cruz D, Bobek I et al (2010) NGAL: a biomarker of acute kidney injury and other systemic conditions. Int Urol Nephrol 42:141–150PubMedCrossRef
21.
go back to reference 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 39:1231–1237PubMedCentralPubMedCrossRef 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 39:1231–1237PubMedCentralPubMedCrossRef
22.
go back to reference 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 273:4135–4142PubMedCrossRef 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 273:4135–4142PubMedCrossRef
23.
go back to reference 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 62:237–244PubMedCrossRef 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 62:237–244PubMedCrossRef
24.
go back to reference 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 18:904–912PubMedCrossRef 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 18:904–912PubMedCrossRef
25.
go back to reference Nejat M, Pickering JW, Devarajan P et al (2012) Some biomarkers of acute kidney injury are increased in pre-renal acute injury. Kidney Int 81:1254–1262PubMedCentralPubMedCrossRef Nejat M, Pickering JW, Devarajan P et al (2012) Some biomarkers of acute kidney injury are increased in pre-renal acute injury. Kidney Int 81:1254–1262PubMedCentralPubMedCrossRef
26.
go back to reference 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 79:85–92PubMedCrossRef 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 79:85–92PubMedCrossRef
27.
go back to reference Bonventre JV (2009) Kidney injury molecule-1 (KIM-1): a urinary biomarker and much more. Nephrol Dial Transplant 24:3265–3268PubMedCrossRef Bonventre JV (2009) Kidney injury molecule-1 (KIM-1): a urinary biomarker and much more. Nephrol Dial Transplant 24:3265–3268PubMedCrossRef
28.
go back to reference Bernard AM, Vyskocil AA, Mahieu P et al (1987) Assessment of urinary retinol-binding protein as an index of proximal tubular injury. Clin Chem 33:775–779PubMed Bernard AM, Vyskocil AA, Mahieu P et al (1987) Assessment of urinary retinol-binding protein as an index of proximal tubular injury. Clin Chem 33:775–779PubMed
29.
go back to reference 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–S19PubMed 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–S19PubMed
30.
go back to reference 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 33:673–676PubMedCrossRef 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 33:673–676PubMedCrossRef
31.
go back to reference Katagiri D, Doi K, Honda K (2012) Combination of two urinary biomarkers predicts acute kidney injury after adult cardiac surgery. Ann Thorac Surg 93:577–583PubMedCrossRef Katagiri D, Doi K, Honda K (2012) Combination of two urinary biomarkers predicts acute kidney injury after adult cardiac surgery. Ann Thorac Surg 93:577–583PubMedCrossRef
32.
go back to reference 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 24:703–723PubMedCrossRef 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 24:703–723PubMedCrossRef
33.
go back to reference Gauer S, Sichler O, Obermuller N et al (2007) IL-18 is expressed in the intercalated cell of human kidney. Kidney Int 72:1081–1087PubMedCrossRef Gauer S, Sichler O, Obermuller N et al (2007) IL-18 is expressed in the intercalated cell of human kidney. Kidney Int 72:1081–1087PubMedCrossRef
34.
go back to reference Parikh CR, Jani A, Melnikov VY et al (2004) Urinary interleukin-18 is a marker of human acute tubular necrosis. Am J Kidney Dis 43:405–414PubMedCrossRef Parikh CR, Jani A, Melnikov VY et al (2004) Urinary interleukin-18 is a marker of human acute tubular necrosis. Am J Kidney Dis 43:405–414PubMedCrossRef
35.
go back to reference 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 42:557–563PubMedCrossRef 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 42:557–563PubMedCrossRef
36.
go back to reference 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 43:3064–3067PubMedCrossRef 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 43:3064–3067PubMedCrossRef
37.
go back to reference 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 76:213–220PubMedCrossRef 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 76:213–220PubMedCrossRef
38.
go back to reference 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 73:465–472PubMedCrossRef 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 73:465–472PubMedCrossRef
39.
go back to reference 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 61:430–439PubMedCrossRef 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 61:430–439PubMedCrossRef
40.
go back to reference 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–F738PubMedCrossRef 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–F738PubMedCrossRef
41.
go back to reference 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 5:395–401PubMedCrossRef 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 5:395–401PubMedCrossRef
42.
go back to reference Ramesh G, Kwon O, Ahn K (2010) Netrin-1: a novel universal biomarker of human kidney injury. Transplant Proc 42:1519–1522PubMedCrossRef Ramesh G, Kwon O, Ahn K (2010) Netrin-1: a novel universal biomarker of human kidney injury. Transplant Proc 42:1519–1522PubMedCrossRef
43.
go back to reference 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:R25PubMedCrossRef 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:R25PubMedCrossRef
Metadata
Title
Current developments in early diagnosis of acute kidney injury
Authors
Nicholas Obermüller
Helmut Geiger
Christine Weipert
Anja Urbschat
Publication date
01-01-2014
Publisher
Springer Netherlands
Published in
International Urology and Nephrology / Issue 1/2014
Print ISSN: 0301-1623
Electronic ISSN: 1573-2584
DOI
https://doi.org/10.1007/s11255-013-0448-5

Other articles of this Issue 1/2014

International Urology and Nephrology 1/2014 Go to the issue