title: Blood kidney injury molecule-1 is a biomarker of acute and chronic kidney injury and predicts progression to ESRD in type I diabetes.
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.
authors.affiliation: Renal Division, Department of Medicine and.
authors.forename: Venkata S
authors.initials: VS
authors.lastname: Sabbisetti
authors.affiliation: Renal Division, Department of Medicine and.
authors.forename: Sushrut S
authors.initials: SS
authors.lastname: Waikar
authors.affiliation: MRC Centre for Drug Safety Science, Department of Molecular & Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom;
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Antoine
authors.affiliation: Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts;
authors.forename: Adam
authors.initials: A
authors.lastname: Smiles
authors.affiliation: Renal Division, Department of Medicine and.
authors.forename: Chang
authors.initials: C
authors.lastname: Wang
authors.affiliation: Renal Division, Department of Medicine and.
authors.forename: Abinaya
authors.initials: A
authors.lastname: Ravisankar
authors.affiliation: Renal Division, Department of Medicine and.
authors.forename: Kazumi
authors.initials: K
authors.lastname: Ito
authors.affiliation: Renal Division, Department of Medicine and.
authors.forename: Sahil
authors.initials: S
authors.lastname: Sharma
authors.affiliation: Renal Division, Department of Medicine and.
authors.forename: Swetha
authors.initials: S
authors.lastname: Ramadesikan
authors.affiliation: Program in Translational NeuroPsychiatric Genomics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts;
authors.forename: Michelle
authors.initials: M
authors.lastname: Lee
authors.affiliation: Program in Translational NeuroPsychiatric Genomics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts;
authors.forename: Rebeccah
authors.initials: R
authors.lastname: Briskin
authors.affiliation: Program in Translational NeuroPsychiatric Genomics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts;
authors.forename: Philip L
authors.initials: PL
authors.lastname: De Jager
authors.affiliation: Renal Division, Department of Medicine and.
authors.forename: Thanh Thu
authors.initials: TT
authors.lastname: Ngo
authors.affiliation: Renal Division, Department of Medicine and.
authors.forename: Mark
authors.initials: M
authors.lastname: Radlinski
authors.affiliation: British Heart Foundation for Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom; and.
authors.forename: James W
authors.initials: JW
authors.lastname: Dear
authors.affiliation: MRC Centre for Drug Safety Science, Department of Molecular & Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom;
authors.forename: Kevin B
authors.initials: KB
authors.lastname: Park
authors.affiliation: Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Betensky
authors.affiliation: Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts;
authors.forename: Andrzej S
authors.initials: AS
authors.lastname: Krolewski
authors.affiliation: Renal Division, Department of Medicine and vsabbisetti@partners.org joseph_bonventre@hms.harvard.edu.
authors.forename: Joseph V
authors.initials: JV
authors.lastname: Bonventre
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D015815:Cell Adhesion Molecules / Q000097:blood*; D003922:Diabetes Mellitus, Type 1 / Q000150:complications; D003928:Diabetic Nephropathies / Q000097:blood; D005260:Female; D000072596:Hepatitis A Virus Cellular Receptor 1; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood*; D008565:Membrane Proteins / Q000097:blood*; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D017207:Rats, Sprague-Dawley; D011991:Receptors, Virus / Q000097:blood*; D051437:Renal Insufficiency / Q000097:blood*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D015815:Cell Adhesion Molecules; D000072596:Hepatitis A Virus Cellular Receptor 1; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D011991:Receptors, Virus; C491143:HAVCR1 protein, human; C442240:Havcr1 protein, mouse; C110936:Havcr1 protein, rat
keywords: acute renal failure; chronic kidney disease; chronic kidney failure; nephrotoxicity