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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

1
Renal Division, Department of Medicine and.
2
MRC Centre for Drug Safety Science, Department of Molecular & Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom;
3
Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts;
4
Program in Translational NeuroPsychiatric Genomics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts;
5
British Heart Foundation for Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom; and.
6
Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts.
7
Renal Division, Department of Medicine and vsabbisetti@partners.org joseph_bonventre@hms.harvard.edu.

Abstract

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.

KEYWORDS:

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

PMID:
24904085
PMCID:
PMC4178434
DOI:
10.1681/ASN.2013070758
[Indexed for MEDLINE]
Free PMC Article

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