Journal
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
Volume 25, Issue 10, Pages 2177-2186Publisher
AMER SOC NEPHROLOGY
DOI: 10.1681/ASN.2013070758
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Funding
- National Institutes of Health (NIH) [DK39773, DK072381, DK075941]
- Gene Expression & Regulatory Networks in Human Leukocytes at the Brigham and Women's Hospital [RC2 GM093080]
- Juvenile Diabetes Research Foundation [1-2008-1018]
- NIH [DK041526]
- CKD Biomarker Consortium [U01-DK85660]
- Medical Research Council via Centre for Drug Safety Science [G0700654]
- Royal Society
- Wellcome Trust
- Medical Research Council [G0700654, MR/L006758/1] Funding Source: researchfish
- MRC [G0700654, MR/L006758/1] Funding Source: UKRI
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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.
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