Clinical Remission as a Function of Exposure to Cyclophosphamide in Patients with Primary Membranous Nephropathy: A One-year Cohort Study

Introduction: Primary membranous nephropathy (pMN) is a leading cause of nephrotic syndrome (NS) in adults. Cyclophosphamide (CYC) with glucocorticoids (GC) are recommended for high and very high-risk patients, but the optimal treatment duration and cumulative dose remain unclear. This study aimed to compare the effectiveness and safety of short-duration (SD) versus long-duration (LD) oral CYC regimens in pMN patients with NS. Methods: We conducted a multi-center retrospective cohort study of 54 adult patients with biopsy-proven pMN treated with oral CYC in the United States and India between 2010–2022. Patients received either SD-CYC (≤3 months) or LD-CYC (>3 months). The primary outcome was overall remission (complete or partial) at 12 months. Secondary outcomes included complete remission (CR) rates and adverse events. Analyses were stratified by treatment duration and cumulative CYC dose. Results: Overall remission at 12 months was similar between SD and LD groups (73% vs. 83%, p=0.088), with a trend toward higher CR in the LD group (47% vs. 23%, p=0.077). The SD group had more baseline chronic kidney changes, which may have impacted outcomes. By cumulative dose, patients receiving >3g CYC had significantly higher overall remission and CR after adjustment for baseline characteristics and cumulative glucocorticoid dose. Serious adverse events occurred in 18.5% of patients, with no significant differences between groups. Conclusion: Short-term oral CYC combined with GC may be a safe alternative to LD-CYC regimens for achieving clinical remission in pMN. Although these findings align with recent evidence supporting the efficacy of low-dose CYC in pMN, well-designed clinical trials are still needed for more robust clinical validation.