Outcomes in Membranous Nephropathy Treated with Intravenous Cyclophosphamide and Oral Prednisolone (Modification of the Modified Ponticelli Regimen): A Single-Centre Experience

Background: The Modified Ponticelli regime (MPR) is established treatment for membranous nephropathy (MN). We modified this at our centre to use oral Prednisolone 40mg daily (months 1, 3, 5) and intravenous Cyclophosphamide (CP) (single dose at start of months 2, 4, 6). This reduces CP and corticosteroid (CS) exposure as compared to the MPR. We analysed our data to see whether our approach negatively impacted remission and relapse rates. Methods: Individuals treated with our modified regimen between 2005 and 2024 were identified. Follow-up continued until the most recent clinic visit at our centre, change in immunosuppressive therapy, or death (whichever happened first). Primary outcomes were: partial remission (PR), defined as > 50% drop in proteinuria from baseline AND urine PCR (uPCR) of 30-350 g/mol; complete remission (CR), defined as uPCR <30 g/mol; relapse, defined as recurrence of uPCR >350 g/mol. All were confirmed on at least 2 consecutive samples. An adverse renal outcome was included as a secondary outcome, defined as dialysis-dependence or a >50% decline in GFR from baseline. Results: 44 individuals commenced our MPR at a median of 4.5 months from diagnosis: 80% were male, 81% were of white ethnicity and the median age was 65 (IQR 58-69) years. 55% were serum PLA2R antibody positive. 39 (87%) completed the full course with a mean total CP dose of 3.1 g (range 1.3-4.5g). The median follow-up period was 1.8 years (IQR.1.0-4.1). 25 (64.1%) achieved remission, and 8 (20.51%) had CR. 7/25 (28%) experienced a relapse during the follow-up period. An adverse renal outcome occurred in 4/14 (29%) of those who did not attain remission, compared to 1/25 (4%) in those who achieved at least PR. The mean rate of eGFR change in those who achieved remission was 2.0 mL/min/year and -9.7 mL/min/year in those who did not (P < 0.01). Conclusion: Our modified MPR achieved comparable remission rates, relapse rates and renal outcomes to those reported with the standard MPR and other regimes that use much higher doses of CP and CS.