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

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...

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Published in:Journal of the American Society of Nephrology Vol. 25; no. 10; p. 2177
Main Authors: Sabbisetti, Venkata S, Waikar, Sushrut S, Antoine, Daniel J, Smiles, Adam, Wang, Chang, Ravisankar, Abinaya, Ito, Kazumi, Sharma, Sahil, Ramadesikan, Swetha, Lee, Michelle, Briskin, Rebeccah, De Jager, Philip L, Ngo, Thanh Thu, Radlinski, Mark, Dear, James W, Park, Kevin B, Betensky, Rebecca, Krolewski, Andrzej S, Bonventre, Joseph V
Format: Journal Article
Language:English
Published: United States 01.10.2014
Subjects:
Adult
Aged
Aged, 80 and over
Animals
Biomarkers - blood
Case-Control Studies
Cell Adhesion Molecules - blood
Diabetes Mellitus, Type 1 - complications
Diabetic Nephropathies - blood
Female
Hepatitis A Virus Cellular Receptor 1
Humans
Male
Membrane Glycoproteins - blood
Membrane Proteins - blood
Mice, Inbred BALB C
Middle Aged
Rats, Sprague-Dawley
Receptors, Virus - blood
Renal Insufficiency - blood
Young Adult
chronic kidney disease
acute renal failure
nephrotoxicity
chronic kidney failure
ISSN:1533-3450, 1533-3450
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Summary: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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ISSN:1533-3450
1533-3450
DOI:10.1681/ASN.2013070758