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J Am Soc Nephrol. 2014 Oct;25(10):2177-86. doi: 10.1681/ASN.2013070758. Epub 2014 Jun 5.

Blood kidney injury molecule-1 is a biomarker of acute and chronic kidney injury and predicts progression to ESRD in type I diabetes.

Author information

Renal Division, Department of Medicine and.
MRC Centre for Drug Safety Science, Department of Molecular & Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom;
Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts;
Program in Translational NeuroPsychiatric Genomics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts;
British Heart Foundation for Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom; and.
Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts.
Renal Division, Department of Medicine and


Currently, no blood biomarker that specifically indicates injury to the proximal tubule of the kidney has been identified. Kidney injury molecule-1 (KIM-1) is highly upregulated in proximal tubular cells following kidney injury. The ectodomain of KIM-1 is shed into the lumen, and serves as a urinary biomarker of kidney injury. We report that shed KIM-1 also serves as a blood biomarker of kidney injury. Sensitive assays to measure plasma and serum KIM-1 in mice, rats, and humans were developed and validated in the current study. Plasma KIM-1 levels increased with increasing periods of ischemia (10, 20, or 30 minutes) in mice, as early as 3 hours after reperfusion; after unilateral ureteral obstruction (day 7) in mice; and after gentamicin treatment (50 or 200 mg/kg for 10 days) in rats. In humans, plasma KIM-1 levels were higher in patients with AKI than in healthy controls or post-cardiac surgery patients without AKI (area under the curve, 0.96). In patients undergoing cardiopulmonary bypass, plasma KIM-1 levels increased within 2 days after surgery only in patients who developed AKI (P<0.01). Blood KIM-1 levels were also elevated in patients with CKD of varous etiologies. In a cohort of patients with type 1 diabetes and proteinuria, serum KIM-1 level at baseline strongly predicted rate of eGFR loss and risk of ESRD during 5-15 years of follow-up, after adjustment for baseline urinary albumin-to-creatinine ratio, eGFR, and Hb1Ac. These results identify KIM-1 as a blood biomarker that specifically reflects acute and chronic kidney injury.


acute renal failure; chronic kidney disease; chronic kidney failure; nephrotoxicity

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