Background: Although remission is achieved in most children with nephrotic syndrome by treatment with corticosteroids, a significant proportion of patients experience relapses. Continuous or repeated use of corticosteroids inevitably induces features of steroid side-effects. Cyclosporin (CsA) has been used in the treatment of idiopathic steroid-dependent and -resistant nephrotic syndrome. However, relapse often occurs shortly after the CsA treatment is terminated. Furthermore, long-term clinical outcome of patients treated with CsA is unclear.
Methods: We retrospectively reviewed the data of 106 nephrotic children having primary focal segmental glomerulosclerosis (FSGS) who received CsA between 1993 and 2002. Indications of CsA therapy were steroid resistance (n = 45) and steroid dependence with steroid toxicity (n = 61). Fifty-four patients received cyclophosphamide prior to CsA therapy. CsA starting dose was 6 mg/kg/day to be readjusted to maintain a whole blood trough level of 80-150 ng/ml. The drug was received for 6-48 months (mean: 22.1+/-11 months). The observation period was 5.8+/-3 and 6.1+/-1.9 years before and after CsA treatment, respectively.
Results: Complete remission [proteinuria <4 mg/h/m2 body surface area (BSA)], partial remission (proteinuria 4.1-40 mg/h/m2 BSA) and resistance to CsA (proteinuria > or =45 mg/h/m2 BSA) were observed in 71.7, 7.5 and 20.8% of patients, respectively. CsA-sensitive and -resistant patients differed only in the percentage of steroid responsiveness, being 66.7% in the former group and 22.7% in the later (P<0.0001). Logistic regression analysis identified steroid resistance as the only predictor of resistance to CsA (odds ratio: 12.9; P = 0.03). Hypertension, renal impairment (>30% rise of serum creatinine), gingival hyperplasia and hypertrichosis occurred in 12.3, 6.6, 22.6 and 51.9% of patients, respectively. With the exception of hypertrichosis, side effects were significantly more frequent among CsA-resistant children. We were able to stop steroids in 91 patients, of whom 31 patients relapsed. Out of 20 patients for whom CsA was intentionally discontinued while in remission, 16 patients relapsed. Of these, four (25%) were resistant to a second course of CsA. At the last follow-up, one child had developed end-stage renal failure and three had chronic renal insufficiency.
Conclusions: CsA is effective in the treatment of children with idiopathic FSGS, but with a high relapse rate on drug withdrawal. Renal dysfunction and hypertension, which may be drug-induced or natural progression, are the most serious complications; therefore, close monitoring is essential.