Mechanistic biomarkers for cytotoxic acute kidney injury

Abstract

Acute kidney injury is a common condition and is associated with a high mortality rate. It has been recognised that routinely used measures of renal function, such as levels of blood urea nitrogen and serum creatinine, increase significantly only after substantial kidney injury occurs and then with a time delay. Insensitivity of such tests delays the diagnosis in humans, making it particularly challenging to administer putative therapeutic agents in a timely fashion. Furthermore, this insensitivity affects the evaluation of toxicity in preclinical studies by allowing drug candidates, which have low, but nevertheless important, nephrotoxic side effects in animals, to pass the preclinical safety criteria only to be found to be clinically nephrotoxic with great human costs. This review presents the current status of sensitive and specific biomarkers to detect preclinical and clinical renal injury and summarises the techniques used to quantitate these biomarkers in biological fluids.

Keywords::

• acute kidney injury
• acute renal failure
• biomarkers
• clusterin
• CYR 61
• cystatin C
• cysteine-rich protein-61
• ELISA
• IL-18
• kidney injury molecule-1
• Kim-1
• microfluidics
• nanotechnology
• neutrophil gelatinase-associated lipocalin
• NGAL

Acknowledgement

Dr Vaidya is supported by Scientist Development Grant 0535492T from the American Heart Association and Dr Bonventre is supported by NIH grants DK-39773, DK-72381 and DK-74099.