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  • Title: Long-term effects of cyclosporine in children with idiopathic nephrotic syndrome: a single-centre experience.
    Author: El-Husseini A, El-Basuony F, Mahmoud I, Sheashaa H, Sabry A, Hassan R, Taha N, Hassan N, Sayed-Ahmad N, Sobh M.
    Journal: Nephrol Dial Transplant; 2005 Nov; 20(11):2433-8. PubMed ID: 16204303.
    Abstract:
    BACKGROUND: Because of its potential nephrotoxicity, the long-term use of cyclosporine (CsA) as treatment for nephrotic syndrome (NS) is controversial. The clinical outcome of the patients with NS treated with CsA is unclear. METHODS: This study reports the results of long-term CsA treatment in 117 children with idiopathic NS, who received CsA therapy for more than 2 years (median, 34 months). The mean age of children at initiation of CsA therapy was 11+/-4 years. The starting dose of CsA was 5 mg/kg/day, adjusted to maintain a trough level of 100-150 ng/ml in the first 2 months, 50-100 ng/ml thereafter. Later, a level as low as 30 ng/ml was accepted so long as it maintained remission. All patients received CsA between 1993 and 2003. Indications for treatment included steroid-dependent nephrotic syndrome (SDNS) in 74 patients and steroid-resistant nephrotic syndrome (SRNS) in 43 patients. Initial renal histology showed minimal change disease (MCD) in 38 patients and focal segmental glomerulosclerosis (FSGS) in 79 patients. Most patients were receiving moderate doses of prednisone. Sixty patients received cyclophosphamide prior to CsA. The observation periods were 5.8+/-3 years 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 between 4.1 and 40 mg/h/m2/BSA) and resistance to CsA (proteinuria > or = 45 mg/h/m2/BSA) were observed in 82.1, 5.1 and 12.8%, respectively. Hypertension, renal impairment (>30% rise of serum creatinine), gingival hyperplasia and hypertrichosis occurred in 10.3, 6.0, 32.5 and 70.1%, respectively. Steroids were stopped in 102 patients, of which 31 relapsed. Out of 29 patients for whom CsA was intentionally discontinued while in remission, 22 relapsed. Of these, six patients were resistant to a second course of CsA. Post-therapy biopsies, performed in 45 patients (33 with SDNS and 12 with SRNS), showed mild stripped interstitial fibrosis and tubular atrophy in two SDNS patients (4.4%). At the last follow-up, one child had developed end-stage renal failure and two had chronic renal insufficiency. CONCLUSIONS: Long-term CsA therapy in low doses is effective in the treatment of children with idiopathic NS, but the rate of relapse is high after drug withdrawal. Hypertension developed in 10% of patients and renal insufficiency in 6% (most patients with FSGS).
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