Urinary kidney injury molecule-1 (Kim-1): a sensitive quantitative biomarker for early detection of kidney tubular injury

Sensitive and specific biomarkers are needed to detect early kidney injury. The objective of the present work was to develop a sensitive quantitative urinary test to identify renal injury in the rodent to facilitate early assessment of pathophysiological influence and drug toxicity. Two mouse monoclonal antibodies were made against the purified ectodomain of kidney injury molecule-1 (Kim-1) and these were used to construct a sandwich Kim-1 ELISA. The assay range of this ELISA was 50 pg/ml to 5 ng/ml with the interand intraassay variability of less than 10 %. Urine samples were collected from rats treated with one of three doses of cisplatin (2.5, 5, or 7.5 mg/kg). At one day after each of the doses there was ~ 3-5-fold increase in urine Kim-1 whereas other routinely used biomarkers measured in this study {plasma creatinine, BUN, urinary N-acetyl-βglucosaminidase (NAG), glycosuria, proteinuria} lacked the sensitivity to show any sign of renal damage at this time point. When rats were subjected to increasing periods (10, 20, 30 or 45 min) of bilateral ischemia there was increasing amount of urinary Kim-1 detected. After only 10 min of bilateral ischemia, Kim-1 levels on day 1 were 10-fold higher (5 ng/ml) than control levels whereas plasma creatinine and BUN were not increased and there was no glycosuria, increased proteinuria or increased urinary NAG levels. Thus, urinary Kim-1 levels serve as a non-invasive, rapid, sensitive, reproducible, and potentially high throughput method to detect early kidney injury in pathophysiological studies and in preclinical drug development studies for risk-benefit profiling of pharmaceutical agents.