Induction and long-term treatment with cyclosporine in membranous nephropathy with the nephrotic syndrome

Background. Cyclosporine A (CyA) has been shown to be effective in membranous nephropathy (MN). However, the optimal dose and the duration of treatment remain controversial issues. We evaluated the efficacy of low-dose CyA alone or combined with corticosteroids as induction and long-term treatment for nephrotic patients with MN. Methods. In the first part of the study, 51 nephrotic patients with MN were treated either with CyA and prednisolone (n = 31) or CyA alone (n = 20) for 12 months. Patients who responded with complete remission (CR) or partial remission (PR) were placed on long-term treatment with lower doses of CyA and prednisolone or CyA alone. The mean follow-up of the second part of the study was 26 +/- 16 months and 18 +/- 7 months, respectively. Results. After 12 months of treatment, 26 patients in the combination group and 17 patients in the monotherapy group had a CR or PR of proteinuria (P = NS). Renal function was unchanged in the two groups. During long-term treatment relapses were more frequent in the monotherapy group (47 vs 15%, P < 0.05). Daily CyA dose was higher in non-relapsers in both groups (combination 1.4 +/- 0.5 vs 1.0 +/- 0.3 mg/kg, P < 0.001, monotherapy 1.5 +/- 0.4 vs 1.1 +/- 0.2 mg/kg, P < 0.003). Relapsers in both groups had lower CyA trough levels (72 +/- 48 ng/ml) compared with non-relapsers (194 +/- 80 ng/ml) (P < 0.03). Renal function and proteinuria remained stable during the follow-up. Conclusion. This study suggests that 12-month therapy with CyA (+/- prednisolone) is effective in inducing remission in most nephrotic patients with MN and well-preserved renal function. Longer treatment with lower doses is a useful approach to maintain remission. Relapses occur more frequently in the monotherapy group and usually are associated with CyA trough levels < 100 ng/ml.