Pancreas-kidney recipients (SPK) are at higher risk for rejection than diabetic kidney-alone recipients (KA), and thus generally receive higher doses of maintenance immunosuppression. This has lead to concern that the potential benefits to renal function, brought about by posttransplant euglycemia, may be negated by the nephrotoxicity of immunosuppression. We therefore sought to compare patterns of renal function in diabetic patients following SPK and KA transplantation. Serum creatinine levels, corrected glomerular filtration rates (cGFR), and whole blood TDX cyclosporine levels were recorded on 25 SPK and 17 KA at 3, 6, 12, and 24 months posttransplant when patients were free of acute renal dysfunction. The SPK recipients had significantly higher cyclosporine levels at each of the measurement points as compared with the KA recipients (P < or = .01). In spite of these higher cyclosporine levels, the SPK recipients showed stable creatinine and cGFR levels throughout the study, as did the KA group until 24 months. At 24 months, the KA group experienced a rise in creatinine from 1.3 +/- .09 ng/dl at 3 months to 1.6 +/- .07 ng/dl at 24 months (P < or = 0.006). Urine albumin excretion was examined at 24 months, and 6 of 8 KA patients found to have abnormally elevated levels compared with only 3 of 9 SPK patients. These findings indicate that SPK recipients experience stable renal function despite significantly higher cyclosporine levels, while KA recipients demonstrate early signs of deteriorating function at the 2-year follow-up.