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

In a prospective randomized study including 100 kidney transplant recipient s, we previously reported on the safety and financial benefits of the coadm inistration of ketoconazole (keto) to cyclosporine (CsA)-treated kidney tra nsplant recipients, In this study, we report on the long-term follow-up of these patients and their control group, as well as possible metabolic conse quences of this drug combination. Evaluation of 51 keto-treated patients en d their control group (49 patients) included graft function, lipogram, tast ing blood glucose, liver function tests, serum calcium, phosphorus, and rad iological and histopathologic assessments. Follow-up of these patients for 54 months showed that the CsA dose reduction was 72.9% at 12 months, decrea sed to 69.3% at the last follow-up. We also found that the mean keto dose r equired for CsA dose reduction decreased to 82.8 +/- 24.1 mg/d compared wit h the starting dose (100 mg/d). Diagnosis of acute rejection episodes was s imilar in both groups. However, in the control group, rejection episodes we re more recurrent, with poorer response to treatment. Acute CsA nephrotoxic ity was more common in the keto group, but this was encountered more at ket o induction and was rapidly reversed on further reduction of CsA doses. Chr onic graft dysfunction was statistically significantly less In the keto gro up during the first year. However, by the end of the study, the difference was not statistically significant. in this study, hepatotoxicity was simila r in the two groups. On studying the metabolic consequences, we found that serum cholesterol, low-density lipoprotein, and triglyceride levels were lo wer 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 tran splant recipients is safe and cost-saving and may induce better graft funct ion. Bone mineral contents, vitamin D blood levels, and lipid profiles are not affected by long-term keto coadministration in CsA-treated kidney trans plant recipients. (C) 2001 by the National Kidney Foundation, Inc.