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


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Abstract

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.

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