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1 Renal Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
2 Molecular Physiology Unit, Instituto de Investigaciones Biomiedicas, Universidad Nacional Autonoma de Mexico and Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico, Mexico
* To whom correspondence should be addressed. E-mail: joseph_bonventre{at}hms.harvard.edu.
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 inter- and 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-
-
glucosaminidase (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.
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