Renal Glycosuria without Hyperglycemia in Cyclosporine-Treated Rats

Abstract

The pathogenesis of post-transplant diabetes mellitus is thought to be partly related to the direct toxic effect of cyclosporine on pancreatic β-cells and the resultant decrease in insulin synthesis and secretion. As a result of hyperglycemia , glycosuria may be found in cyclosporine administration. However, mechanism of glycosuria in cyclosporine nephrotoxicity was not clear Methods: Cyclosporine was subcutaneously injected to male Sprague-Dawley rats at a daily dose of 7.5 mg/kg (n=6) for 6 weeks. Biochemical data were obtained from urine and plasma samples. Results: Cyclosporine treatment caused a remarkable increase in urine volume and a decrease in urine osmolality. Urinary excretion of glucose was remarkably elevated by cyclosporine administration (7±3.0 mg/dL versus 12896±3218 mg/dL; P < 0.005). Plasma glucose levels at the end of animal experiment were not affected by cyclosporine administration (117 ± 40.6 mg/dL versus 114 ±26.0 mg/dL; NS). Vehicle-treated controls had a larger final BW than cyclosporine-treated (309±17 g versus 275±13 g; p < 0.01), steady weight gain was obtained in both groups. We did not find any evidence of generalized proximal tubular dysfunction Conclusion: Glycosuria may occur without hyperglycemia in cyclosporine administration. We suggest that cyclosporine may decrease tubular reabsorption of glucose in renal tubular epithelial cells, and then glycosuria could be induced by the altered glucose transporter expressions. We will analyze the glucose transporters in proximal tubule of rat kidney.