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, 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 journalArticle

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.

Original languageEnglish (US)
Pages (from-to)2177-2186
Number of pages10
JournalJournal of the American Society of Nephrology
Volume25
Issue number10
DOIs
StatePublished - Oct 1 2014

ASJC Scopus subject areas

  • Nephrology

Fingerprint Dive into the research topics of 'Blood kidney injury molecule-1 is a biomarker of acute and chronic kidney injury and predicts progression to ESRD in type I diabetes'. Together they form a unique fingerprint.

  • Cite this

    Sabbisetti, V. S., Waikar, S. S., Antoine, D. J., Smiles, A., Wang, C., Ravisankar, A., Ito, K., Sharma, S., Ramadesikan, S., Lee, M., Briskin, De Jager, P. L., Ngo, T. T., Radlinski, M., Dear, J. W., Park, K. B., Betensky, R., Krolewski, A. S., & Bonventre, J. V. (2014). Blood kidney injury molecule-1 is a biomarker of acute and chronic kidney injury and predicts progression to ESRD in type I diabetes. Journal of the American Society of Nephrology, 25(10), 2177-2186. https://doi.org/10.1681/ASN.2013070758