Cyclosporin A in the treatment of childhood glomerulonephritis

Abstract

Seven children with steroid resistant nephrotic syndrome (focal segmental sclerosis in six, mesangial proliferation in one) were treated with Cyclosporin A for 12 weeks. Five of these children were also resistant to cyclophosphamide. All patients had normal renal function. Cyclosporin was started at 8 mg/kg/day then increased until a trough blood level of 100-300 ng/ml (HPLC) was achieved. Three of the seven patients achieved complete remission, and the other four had a significant reduction in their proteinuria (p less than 0.05). In the three patients who achieved complete remission, relapse of proteinuria occurred within six weeks of ceasing Cyclosporin. All patients experienced some impairment in renal function with mean creatinine clearance decreasing from 129 +/- 19 to 91 +/- 13 ml/min/1.73m2 (p less than 0.05). One child was subsequently treated with Cyclosporin for 12 months. He remains in remission with a repeat renal biopsy showing no evidence of nephrotoxicity. One other child with steroid sensitive minimal change nephrotic syndrome who had severe steroid toxicity was treated with a lower dose (5 mg/kg/day) for 12 months. She remained in remission off steroids, but relapsed 16 weeks after Cyclosporin was ceased. A renal biopsy after 12 months showed no nephrotoxicity. Cyclosporin should be considered in steroid resistant nephrotic syndrome, and in children with minimal change disease who show signs of steroid toxicity and short remission period after cyclophosphamide. Serial renal biopsies are recommended with prolonged therapy.