Biomarkers of drug-induced kidney toxicity.

Blood urea nitrogen (BUN) and serum creatinine are imperfect markers of kidney function because they are influenced by many renal and non-renal factors independent of kidney function. A biomarker that is released directly into the blood or urine by the kidney in response to injury may be a better early marker of drug-induced kidney toxicity than BUN and serum creatinine. Urine albumin and urine protein, as well as urinary markers kidney injury molecule-1 (KIM-1), β2-microglobulin (B2M), cystatin C, clusterin, and trefoil factor-3 (TFF-3) have been accepted by the Food and Drug Administration (FDA) and European Medicines Agency as highly sensitive and specific urinary biomarkers to monitor drug-induced kidney injury in preclinical studies and on a case-by-case basis in clinical trials. Other biomarkers of drug-induced kidney toxicity that have been detected in the urine of rodents or patients include IL-18 (interleukin-18), NGAL (neutrophil gelatinase-associated lipocalin), Netrin-1, liver type fatty acid binding protein (L-FABP), urinary exosomes, and TIMP2 (insulin-like growth factor -binding protein 7)/IGFBP7 (insulin-like growth factor binding protein 7), also known as NephroCheck®, the first FDA-approved biomarker testing platform to detect acute kidney injury (AKI) in patients. In the future, a combined use of functional and damage markers may advance the field of biomarkers of drug kidney toxicity. Earlier detection of drug-induced kidney toxicity with a kidney specific biomarker may result in the avoidance of nephrotoxic agents in clinical studies and may allow for earlier intervention to repair damaged kidneys.