Is low-dose ciclosporin an effective treatment for membranous nephropathy with nephrotic syndrome?

    loading  Checking for direct PDF access through Ovid


SYNOPSISBACKGROUNDCiclosporin has shown promise in the treatment of idiopathic membranous nephropathy (IMN) at a dose of 4-6 mg/kg.OBJECTIVETo evaluate the efficacy of low-dose ciclosporin, with and without prednisolone, for induction and maintenance treatment of IMN combined with nephrotic syndrome.DESIGNThe inclusion criteria for this Greek study were biopsy-proven membranous nephropathy and nephrotic syndrome (proteinuria >3 g/24 h and plasma albumin level <30 g/l [<3 g/dl]). Individuals with diabetes mellitus or a serum creatinine level >177 μmol/l (>2 mg/dl) at presentation and those who were seropositive for hepatitis B antigen were excluded.INTERVENTIONCiclosporin was initiated at 2-3 mg/kg/day upon diagnosis. Dosing was continued for 12 months, with adjustments to achieve a whole-blood trough level of 100-200 ng/ml. Prednisolone (starting dose 0.6 mg/kg/day) was administered to the patients who did not have contraindications for combined therapy. Prednisolone dosing was reduced to 10-15 mg/day for the final 6 months. Follow-up visits took place monthly for the first 6 months and 2-monthly thereafter. Patients who experienced a complete or partial remission after 12 months were eligible to enter a long-term study, in which dosing was reduced to approximately 1.0-1.5 mg/kg/day for ciclosporin and to approximately 0.1 mg/kg/day for prednisolone.OUTCOME MEASURESThe end points were complete remission (decrease in proteinuria to ≤0.3 g/24 h for 2 weeks), partial remission (stable kidney function combined with a decrease in proteinuria of ≥50% and to <3 g/24 h for 2 weeks) and relapse (increase in proteinuria of ≥50% from baseline, or recrudescence of nephrotic syndrome for ≥2 weeks, following complete or partial remission).RESULTSBaseline demographic and laboratory factors did not differ significantly between the patients who received ciclosporin plus prednisolone (n = 31) and those who received ciclosporin only (n = 20). At 12 months, there were no significant differences between the combined therapy group and the ciclosporin-only group in the rates of complete remission (35% vs 20% [11 vs 4]) or partial remission (48% vs 65% [15 vs 13]). Ciclosporin was discontinued in 8 nonresponders. Five of the patients who received ciclosporin and prednisolone, and 1 patient who received ciclosporin only, started antihypertensive therapy during the study. Similar proportions of patients in each group experienced a ≥30% increase in baseline creatinine level (26% [8/31] vs 25% [5/20]). In the long-term study (mean follow-up 26 months in the combined therapy group; 19 months in the monotherapy group), significantly fewer ciclosporin-prednisolone patients than ciclosporin-only patients relapsed (4/26 vs 8/17 [15% vs 47%]; P <0.05). Proteinuria and serum creatinine level remained stable in both groups.CONCLUSIONThe authors concluded that low-dose ciclosporin, with or without prednisolone, was effective at inducing remission of IMN combined with nephrotic syndrome. Addition of prednisolone to ciclosporin maintenance therapy might reduce the risk of long-term relapse.

    loading  Loading Related Articles