EFFECT OF DURATION OF DIABETES ON THE PROTECTION OBSERVED IN THE DIABETIC RAT AGAINST GENTAMICIN-INDUCED ACUTE-RENAL-FAILURE

  • 1 January 1984
    • journal article
    • research article
    • Vol. 10  (3) , 209-216
Abstract
Previously, rats with experimental diabetes (DM) of 4-6 mo. duration exhibit complete functional and morphologic protection against gentamicin-induced acute renal failure. To assess the role of the duration of the diabetic state per se on the resistance to gentamicin, female Sprague-Dawley rats with diabetes of short (5 days, n = 7), intermediate (5 wk, n = 5) and long duration (5 mo., n = 7) were studied. Diabetes was induced by streptozotocin, 50-65 mg/kg b.w. [body wt] i.v. Controls were identically treated sex- and age matched nondiabetic rats. The animals were kept in individual metabolic cages for 2 wk and all received gentamicin 40 mg/kg per day for 9 days. Sham animals (DM and control) received Ringer''s solution in place of gentamicin. Prior to gentamicin, plasma glucose levels and creatinine clearances (Ccr) were higher in the DM long duration group (619 .+-. 25 (SE) mg/dl; 2.6 .+-. 0.2 ml/min, respectively) than in the DM short (514 .+-. 24; 2.0 .+-. 0.1) and DM intermediate duration (442 .+-. 30; 2.1 .+-. 0.1) groups, while urine volume and glycosuria were similar. Following gentamicin the 3 control groups developed acute renal failure (maximal decrease in Ccr of 60 .+-. 7, 72 .+-. 9 and 71 .+-. 7%, respectively; P < 0.01 to < 0.001), lysozymuria and acute tubular necrosis. There were no significant differences in the degree of renal impairment observed among the 3 control groups. In the 3 DM groups these changes were absent and the renal cortical gentamicin was lower than that of the control groups. The duration of diabetes prior to gentamicin treatment does not appear to influence the resistance of the DM rats against gentamicin-induced acute renal failure. The factor(s) responsible for this resistance in the rat with experimental diabetes are fully operative shortly (5 days) after induction of diabetes, and appeared related to the observed decreased renal cortical uptake of gentamicin.