Effect of concomitant administration of cyclosporine and ketoconazole in children with focal segmental glomerulosclerosis.

Background: Focal segmental glomerulonephritis (FSGS) is now the most common primary glomerulonephritis that leads to end-stage renal disease in both adults and children. Cyclosporine (CsA) is a well-known and effective immunosuppressive agent that has become a cornerstone of immunotherapy in solid organ transplantation and it has been used in the treatment of FSGS for over 15 years. The deliberate use of ketoconazole (keto) to reduce the need for CsA is not new, but it is particularly relevant because of the high cost of CsA. Many studies have documented this benefit in renal and cardiac transplants, but this co-administration has not been reported in children with nephrotic syndrome (NS).

Methods: This study included 116 children (below 18 years of age) with primary FSGS who were steroid resistant or dependent and received CsA therapy. Among them, 88 received daily keto therapy (keto group) in a dose of 50 mg with concomitant decrease of CsA dose by one third, while 28 patients received CsA alone (non-keto group). Mean (+/-SD) age was 6.17 +/- 4.68 years and male to female ratio was 1.9:1. The great majority of the study population received the drugs for 1-2 years. The characteristics of both groups were comparable.

Results: Co-administration of keto significantly reduced mean doses of CsA by 46% at 1 year with overall net cost savings of 36%. It also significantly improved the response to CsA therapy and decreased the frequency of renal impairment. No significant side effects for keto were observed.

Conclusion: Co-administration of keto and CsA in idiopathic FSGS children is safe. This combination not only reduces the costs but also may improve the response to CsA and stabilize the renal function.