Coadministration of ketoconazole and cyclosporine for kidney transplant recipients: long-term follow-up and study of metabolic consequences.

摘要

In a prospective randomized study including 100 kidney transplant recipients, we previously reported on the safety and financial benefits of the coadministration of ketoconazole (keto) to cyclosporine (CsA)-treated kidney transplant recipients. In this study, we report on the long-term follow-up of these patients and their control group, as well as possible metabolic consequences of this drug combination. Evaluation of 51 keto-treated patients and their control group (49 patients) included graft function, lipogram, fasting blood glucose, liver function tests, serum calcium, phosphorus, and radiological and histopathologic assessments. Follow-up of these patients for 54 months showed that the CsA dose reduction was 72.9% at 12 months, decreased to 69.3% at the last follow-up. We also found that the mean keto dose required for CsA dose reduction decreased to 82.8 +/- 24.1 mg/d compared with the starting dose (100 mg/d). Diagnosis of acute rejection episodes was similar in both groups. However, in the control group, rejection episodes were more recurrent, with poorer response to treatment. Acute CsA nephrotoxicity was more common in the keto group, but this was encountered more at keto induction and was rapidly reversed on further reduction of CsA doses. Chronic graft dysfunction was statistically significantly less in the keto group during the first year. However, by the end of the study, the difference was not statistically significant. In this study, hepatotoxicity was similar in the two groups. On studying the metabolic consequences, we found that serum cholesterol, low-density lipoprotein, and triglyceride levels were lower in the keto group. Bone mineral contents in both groups were less than the mean values for age- and sex-matched healthy controls. From this study, we conclude that long-term use of low-dose keto in CsA-treated kidney transplant recipients is safe and cost-saving and may induce better graft function. Bone mineral contents, vitamin D blood levels, and lipid profiles are not affected by long-term keto coadministration in CsA-treated kidney transplant recipients.