Glucose-induced increases in renal hemodynamic function. Possible modulation by renal prostaglandins.

Increased glomerular filtration rate and kidney size early in the course of experimental and human diabetes may be important in the pathogenesis of diabetic nephropathy. Factors causing these renal functional changes are unknown. The isolated, perfused rat kidney (IPRK) was used to study the effects of elevated glucose levels on kidneys from normal and diabetic rats in the absence of complex systemic effects of in vivo hyperglycemia. It was found that acute increases in perfusate glucose levels caused sustained dose-dependent vasodilatation in both normal and diabetic isolated kidneys. Furthermore, in normal kidneys, raising perfusate glucose to levels seen in moderately severe diabetes caused increased inulin clearance (Cln). In contrast, equal osmolar concentrations of mannitol caused sustained vasoconstriction and a slight decrease in Cln. Prostaglandin synthetase inhibitors reduced glucose-induced vasodilatation by 50% and prevented the increase in Cln that followed the addition of glucose to normal kidneys. Thus, these studies demonstrated that elevated glucose levels caused significant vasodilatation and increased Cln in the IPRK, and these glucose-induced hemodynamic changes were attenuated by prostaglandin synthetase inhibitors. It is possible that these glucose-induced effects may be important determinants of increased glomerular function in early diabetes.