Randomized Controlled Trial on the Efficacy of Reduced-Dose Cyclical Corticosteroids and Cyclophosphamide in Primary Membranous Nephropathy

Document Type

Article

Publication Title

Kidney International Reports

Abstract

Introduction: The use of cyclophosphamide with corticosteroids for the management of membranous nephropathy (MN) is associated with significant safety concerns. Several retrospective studies suggest that a lower dose may effectively induce remission in participants with MN. This randomized trial assessed whether the lower dose of cyclical cyclophosphamide/corticosteroids was noninferior to the standard dose in patients with MN. Methods: We randomly assigned 114 participants (32 women and 82 men) to receive either the low dose (prednisolone, 0.5 mg/kg/d during months 1, 3, and 5 along with oral cyclophosphamide, 1.0–1.5 mg/kg/d during months 2, 4, and 6) or the standard-dose cyclophosphamide/corticosteroids (methylprednisolone, 1 g/d for 3 days, followed by prednisolone, 0.5 mg/kg/d during months 1, 3, and 5, along with oral cyclophosphamide, 2.0–2.5 mg/kg/d during months 2, 4, and 6). The primary outcome was complete remission (CR) or partial remission (PR) of proteinuria between months 6 and 24. Results: A total of 57 participants were randomized into each group. The mean age was 41.53 ± 12.29 years; median proteinuria, mean serum albumin, and creatinine levels were respectively 6.83 g/d (interquartile range: 5.02–10.15), 2.34 ± 0.58 g/dl, and 0.92 ± 0.26 mg/dl and were comparable between groups. In the intention-to-treat (ITT) analysis, 45 participants (78.94%) in the low-dose group and 50 participants (87.71%) in the standard-dose group achieved the primary outcome (treatment difference: −8.78%, 97.5% confidence interval [CI]: lower limit −22%) and met the criteria for noninferiority (P = 0.009). Forty-five (78.94%) and 55 (96.49%) participants receiving the low-dose and standard-dose cyclophosphamide/corticosteroids, respectively, experienced at least 1 adverse event (difference: −17.54%, 97.5% CI: lower limit −29.1%). Conclusion: The results suggest that low-dose cyclophosphamide/corticosteroids may be as effective as the standard dose of cyclical cyclophosphamide/corticosteroids in achieving proteinuria remission in MN.

First Page

3785

Last Page

3795

DOI

10.1016/j.ekir.2025.08.018

Publication Date

11-1-2025

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