Brief CommunicationsBlood Kidney Injury Molecule-1 Is a Biomarker of Acute and Chronic Kidney Injury and Predicts Progression to ESRD in Type I DiabetesSabbisetti, 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.* Author Information *Renal Division, Department of Medicine and §Program in Translational NeuroPsychiatric Genomics, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts; †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; ‖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 Correspondence: Dr. Venkata Sabbisetti or Dr. Joseph V. Bonventre, Brigham and Women’s Hospital, Harvard Institutes of Medicine, Room 550 or 576, 4 Blackfan Circle, Boston, MA 02115. Email: [email protected] or [email protected] Received July 21, 2013 Accepted March 22, 2014 Journal of the American Society of Nephrology 25(10):p 2177-2186, October 2014. | DOI: 10.1681/ASN.2013070758 Buy Metrics 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. Copyright © 2014 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.