Renal structure and function in streptozotocin-diabetic rats treated with cyclosporin A.

Abstract

The effect of cyclosporin A (CsA), administered daily by gavage at 20 mg/kg body weight, on renal structure and function was investigated in normal and streptozotocin-diabetic male adult Sprague-Dawley rats over 12 weeks. In the non-diabetic animals CsA caused a progressive decrease in glomerular filtration rate and increased enzymuria. In contrast, the diabetic state was associated with massive increases in both enzymuria and urine flow rates, but a trend towards increased urea and creatinine clearance rates. CsA treatment of diabetic animals did not significantly alter the above parameters, nor affect circulating glucose levels, and trough serum CsA concentrations were similar in both diabetic and non-diabetic animals. The kidneys from CsA-treated non-diabetic animals showed chronic tubular damage. In the streptozotocin groups, the only morphological abnormality which could be related to diabetes was excess glycogen deposition in distal renal tubules. CsA-treatment of these groups was not associated with structural enhancement of either the drug's nephrotoxicity or the diabetes-related changes. Indeed the results indicate that the diabetic state affords some protection against the functional aspects of CsA-nephrotoxicity.