Long-term treatment of focal segmental glomerulosclerosis in children with cyclosporine given as a single daily dose

Abstract

Cyclosporine (CsA) has been successfully used for treatment of children with focal segmental glomerulosclerosis (FSGS) and nephrotic syndrome (NS) for the last decade. Response rates of 50% to 100% have been reported using twice-daily dosing of 5 to 32 mg/kg/d, achieving trough blood levels of 70 to 500 ng/mL. Treatment has been associated with a high incidence of side effects, including nephrotoxicity, hypertension, gingival hyperplasia, and hirsutism. To determine whether once-daily low-dose CsA could minimize side effects and still induce remission, 21 children with biopsy-proven FSGS and NS, each treated with CsA, 4.6 +/- 0.8 mg/kg/d, with no predetermined target trough blood levels, were studied. Eleven of 21 children (52%) attained complete remission and 5 of 21 children (24%) attained partial remission, for a total response rate of 76%. Mean time to response was 2.8 +/- 0.8 months, and mean duration of therapy was 20.6 +/- 13.7 months. CsA dosage was tapered or stopped in 9 responders; 3 of these patients maintained remission at last follow-up 6 to 13 months later, and 6 patients relapsed at 1.5 to 18.7 months (mean, 8.7 months). Five of these 6 patients responded again when CsA therapy was restarted or the dosage was increased. Twelve of 16 responders were still being administered CsA at last follow-up 11 to 60 months (mean, 24.6 months) later. Five of 21 patients (24%) had no response to CsA during 2 to 27 months of therapy; 4 of these 5 patients developed end-stage renal disease after CsA therapy was stopped. Side effects of CsA therapy were minimal: 1 patient each developed new-onset hypertension or gingival hyperplasia, and no patient had hirsutism or nephrotoxicity. Single daily low-dose CsA appears to be effective for long-term treatment of children with FSGS and NS, with fewer side effects than twice-daily dosing.