Co-administration of cyclosporine and ketoconazole in children with minimal change nephrotic syndrome.

Background/aims: The use of cyclosporine A (CsA) in the treatment of idiopathic nephrotic syndrome was firstly reported in 1986. On the other hand, many studies have documented the benefit of ketoconazole (keto) administration in renal and cardiac transplant adults treated with CsA, but this co-administration has not been reported in children with minimal change disease (MCD). Thus, deliberate use of keto to reduce the need for cyclosporine is not new, but it is particularly relevant because of the high cost of cyclosporine.

Methods: This study included 46 children with MCD who were steroid resistant or dependent and received CsA. Among them, 31 received daily keto therapy (keto group) in a dose of 50 mg with concomitant decrease of the CsA dose by one third while 15 patients received CsA alone (non-keto group).

Results: The mean (+/-SD) duration of CsA treatment was 25.7 +/- 13.7 months. The characteristics of both groups were comparable. Co-administration of keto significantly improved the response to CsA therapy (from 60 to 94%) and decreased the frequency of renal impairment (from 27 to 3%). Hepatic function remained within the normal range in both groups. Co-administration of keto significantly reduced mean doses of CsA with overall net cost savings of about 34%.

Conclusion: From this study, we may conclude that co-administration of low dose ketoconazole to cyclosporine in children with idiopathic MCD is safe. This combination significantly reduces CsA cost and, moreover, keto may improve the response to cyclosporine and may have a favorable effect on the kidney function.