Long-term outcomes of idiopathic membranous nephropathy in Japanese patients treated with low-dose cyclophosphamide and prednisolone

Background. Treatment with cyclophosphamide and steroids for idiopathic membranous nephropathy (IMN) is effective in Caucasian patients, but the cumulative cyclophosphamide dosage exceeds 10 g and includes steroid pulse therapy. Adverse effects and difficulties with repeating treatment are major limitations. We studied the long-term outcomes of low-dose cyclophosphamide and prednisolone therapy in Japanese patients, who were thought to have relatively benign IMN compared with Caucasian patients. Methods. This is a prospective cohort study of 103 consecutive Japanese patients with IMN and nephrotic syndrome. Patients were treated with cyclophosphamide (50 mg/day for the first 3 months and 25 mg/day for the next 3 months) and prednisolone (30 mg/day for the first week and the dosage was gradually tapered to withdraw by 2 years). Additional therapies were allowed for initial treatment failure or relapse. Results. With a mean observation period of 8.5 years, 90 patients (87.4%) achieved proteinuria of <1 g/day and 78 (75.7%) achieved complete remission. A total of 27 patients did not respond to initial treatment and 30 patients had relapses after remission. Of these patients, 39 received additional therapies. At the last observation, 12 patients had developed renal insufficiency (S-Cr > 1.5 mg/dL) but only 2 patients had reached renal death. Multivariate analysis revealed that the duration without remission was the strongest risk factor for renal prognosis. There were 14 deaths, and 8 patients developed cancers during the observation period. Conclusion. Treating nephrotic IMN in Japanese patients with low-dose cyclophosphamide and prednisolone is beneficial for long-term renal prognosis with relatively few adverse effects.