Do Tubular Changes in the Diabetic Kidney Affect the Susceptibility to Acute Kidney Injury?

Diabetes is the single largest contributor to the growing prevalence of chronic kidney disease (CKD), and episodes of acute kidney injury (AKI) increase the risk of advanced CKD in diabetic patients. Here we discuss whether the pathophysiological changes that occur in the tubular system of the diabetic kidney affect the intrinsic susceptibility to AKI. There is abundant data showing that drug-induced nephrotoxicity is attenuated in rodents with experimental diabetes mellitus, and some mechanistic explanations have been provided, in particular in response to aminoglycosides. Besides downregulation in proximal tubular megalin, which mediates the aminoglycoside uptake in proximal tubules, a role for hyperglycemia-induced activation of regenerative mechanisms has been proposed. The available clinical data, however, indicates that diabetes is a risk factor for AKI, including aminoglycoside nephrotoxicity. While much needs to be learned about this disconnect, the isolated induction of diabetes in otherwise healthy young adult rodents may simply not fully mimic the influence that diabetes exerts in the setting of a critically ill and often elderly patient. We speculate Published online: September 24, 2014 Volker Vallon, MD Division of Nephrology-Hypertension, Departments of Medicine and Pharmacology University of California San Diego, and VA San Diego Healthcare System 3350 La Jolla Village Drive (9151), San Diego, CA 92161 (USA) E-Mail vvallon @ ucsd.edu © 2014 S. Karger AG, Basel 1660–2110/14/1274–0133$39.50/0 www.karger.com/nec Changing Paradigms in Acute Kidney Injury: From Mechanisms to Management – Proceedings of the 5th Annual UAB-UCSD O’Brien Center Symposium (San Diego, Calif., USA, March 4, 2014). D ow nl oa de d by : 54 .1 91 .4 0. 80 6 /7 /2 01 7 2: 04 :3 3 A M