Review: neutrophil gelatinase-associated lipocalin: a troponin-like biomarker for human acute kidney injury.
Acute kidney injury (AKI) is a common and serious condition, the diagnosis of which currently depends on functional markers such as serum creatinine measurements. Unfortunately, creatinine is a delayed and unreliable indicator of AKI. The lack of early biomarkers of structural kidney injury (akin to troponin in acute myocardial injury) has hampered our ability to translate promising experimental therapies to human AKI. Fortunately, understanding the early stress response of the kidney to acute injuries has revealed a number of potential biomarkers. The discovery, translation and validation of neutrophil gelatinase-associated lipocalin (NGAL), possibly the most promising novel AKI biomarker, is reviewed. NGAL is emerging as an excellent stand-alone troponin-like structural biomarker in the plasma and urine for the early diagnosis of AKI, and for the prediction of clinical outcomes such as dialysis requirement and mortality in several common clinical scenarios. The approach of using NGAL as a trigger to initiate and monitor therapies for AKI, and as a safety biomarker when using potentially nephrotoxic agents, is also promising. In addition, it is hoped that the use of sensitive and specific biomarkers such as NGAL as endpoints in clinical trials will result in a reduction in required sample sizes, and hence the cost incurred. Furthermore, predictive biomarkers like NGAL may play a critical role in expediting the drug development process. However, given the complexity of AKI, additional biomarkers (perhaps a panel of plasma and urinary biomarkers) may eventually need to be developed and validated for optimal progress to occur.
Devarajan
Prasad
P
Cincinnati Children's Hospital Medical Center, University of Cincinnati School of Medicine, Cincinnati, Ohio 45229-3039, USA. prasad.devarajan@cchmc.org
D000208:Acute Disease; D000209:Acute-Phase Proteins / Q000652:urine; D015415:Biomarkers / Q000097:blood / Q000652:urine; D006801:Humans; D007674:Kidney Diseases / Q000097:blood / Q000175:diagnosis* / Q000628:therapy / Q000652:urine; D000071068:Lipocalin-2; D054834:Lipocalins / Q000097:blood / Q000652:urine; D011237:Predictive Value of Tests; D011518:Proto-Oncogene Proteins / Q000097:blood / Q000652:urine; D013997:Time Factors; D016896:Treatment Outcome
D000209:Acute-Phase Proteins; D015415:Biomarkers; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins