To determine the effect of
diabetes mellitus on
gentamicin nephrotoxicity we treated male F344 rats with
streptozotocin 22 mg/kg (DM rats). DM rats were compared to controls (C) and nondiabetic rats ingesting the
osmotic diuretic isosorbide administered to simulate glycosuric diuresis (C/I). Base-line C/I renal function and histology did not differ from C. However, in DM rats base-line
inulin clearance (CIN) was 20% lower, and renal cortical slice uptake of
p-aminohippurate was reduced compared to C and C/I. DM rats also had foci of renal tubular epithelial dysplasia not seen in C or C/I.
Gentamicin was administered at 40 mg/kg-day to C and C/I and 32 mg/kg-day to DM rats to adjust for base-line CIN. Acute tubular
necrosis, associated with depression of CIN and renal cortical
p-aminohippurate and
N-methylnicotinamide uptake, developed in all three groups. There were no differences between C and C/I. However, the degree of acute tubular
necrosis and dysfunction was less in DM rats than C and C/I. Renal cortical
gentamicin accumulation was also slower in DM than either C or C/I, and changes in renal cortical
gentamicin over time followed a different pattern in DM rats. These results indicate that 1) attenuation of
gentamicin injury in DM rats may be related to reduced accumulation of
gentamicin by the renal cortex, 2) this reduced accumulation may be due to subtle baseline tubular injury mediated by
streptozotocin or the diabetic state, and 3) osmotic diuresis does not account for attenuation of renal injury in DM.