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

Venkata S Sabbisetti, Sushrut S Waikar, Daniel J Antoine, Adam Smiles, Chang Wang, Abinaya Ravisankar, Kazumi Ito, Sahil Sharma, Swetha Ramadesikan, Michelle Lee, Rebeccah Briskin, Philip L De Jager, Thanh Thu Ngo, Mark Radlinski, James W Dear, Kevin B Park, Rebecca Betensky, Andrzej S Krolewski, Joseph V Bonventre

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.

Original languageEnglish
Pages (from-to)2177-86
Number of pages10
JournalJournal of the American Society of Nephrology
Volume25
Issue number10
DOIs
Publication statusPublished - Oct 2014

Keywords / Materials (for Non-textual outputs)

  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Biomarkers
  • Case-Control Studies
  • Cell Adhesion Molecules
  • Diabetes Mellitus, Type 1
  • Diabetic Nephropathies
  • Female
  • Humans
  • Male
  • Membrane Glycoproteins
  • Membrane Proteins
  • Mice, Inbred BALB C
  • Middle Aged
  • Rats, Sprague-Dawley
  • Receptors, Virus
  • Renal Insufficiency
  • Young Adult

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