Long-term Cyclosporine A(Cypol(R)) Therapy in Children with Idiopathic Nephrotic Syndrome

Hong, Ihn Hee; Ko, Cheol Woo; Koo, Ja Hoon; Cho, Byoung Soo; Kim, Ji Hong; Yook, Jin Won; Kim, Pyung Kil

Abstract

This multicenter collaboratory study was conducted to find out the long-term therapeutic efficacy and side effect of cyclosporine A(Cypol(R), Chong Kun Dang) on children with idiopathic nephrotic syndrome who experienced frequently relapsing(FR), steroid dependent(SD), or steroid resistant(SR) pattern. Forty-six children with SD/FR NS and 5 children with SR NS were enrolled in this study. After induction of remission(SD/FR NS) with steroid or after 4 weeks of steroid therapy(SR NS), cyclosporine A was started in a dose of 4-5mg/kg/day in two divided dose and steroid(prednisolone or equivalent dose of deflazacort) was tapered slowly. During 12 months of study period, monthly check up of physical examination and various laboratory tests including BUN, creatinine, Ccr and cyclosporine blood level were done. Out of 46 children with SD/FR NS, 28(60.9%) maintained sustained remission, 16(34.8%) showed 1 or 2 relapses during therapy and 2(4.3%) cases showed no response. At 4 weeks after therapy, values of serum protein, albumin, cholesterol, and 24 hours urinary protein excretion showed normal values. Four out of 5 children with SR NS showed complete or partial remission with cyclosporine A therapy and one child showed no response. Side reaction to cyclosporine A therapy showed hypertricosis in 14 cases, hyperuricemia in 8 cases and hypomagnesemia in 16 cases. However, other laboratory tests including CBC, liver profile, BUN, creatinine and GFR(creatinine clearance utilizing 24 hour urine) did not show any abnormalities during the 12 months of study period. We performed follow-up renal biopsy in 17 children after 12 months cyclosporine A treatment. Eight cases(47.1%) showed mild cyclosporine A nephrotoxicity like interstitial fibrosis and tubular atropy. In conclusion, present study shows that cyclosporine A(Cypol(R), Chong Kun Dang) can be used quitely effectively in maintaining remission and decreasing relapse rate on children with SD/FR or SR NS. However, because administration of cyclosporine A for 12 months is found to be associated with nephrotoxicity in a significant number of patients, we are planning further study using "smaller dosage" of cyclosporine A to reduce its nephrotoxic effect and for longer period of treatment(over 2 years).