Substitution of oral for intravenous cyclophosphamide in membranous nephropathy

Background: Optimal immunosuppressive treatment for membranous nephropathy is still a matter of controversy. Current recommendations include oral cyclophosphamide combined with steroids (modified Ponticelli regimen) as first-line treatment in high risk patients. However, concerns about the cumulative toxicity of oral cyclophosphamide persist. In the last 30 years, a protocol based on low-dose intravenous cyclophosphamide plus steroids has been used to treat membranous nephropathy in Uruguay. We aimed to assess the efficacy of this regimen to induce clinical remission in patients with membranous nephropathy. Methods: In this retrospective, observational cohort study, we analyzed the outcome of 55 patients with membranous nephropathy treated between 1990 and 2017 with a 6-month course of alternating steroids (months 1, 3 and 5) plus intravenous cyclophosphamide (single dose of 15 mg/kg on the first day of months 2, 4, and 6). Results: At 24 months, 39 (70.9%) patients achieved clinical response with complete remission observed in 23 cases (41.8%) and partial remission in 16 (29.1%). Median time to achieve partial and complete remission was 5.9 and 11.5 months, respectively. Absence of response was observed in 16 patients (29.1%), 5 of which started chronic renal replacement therapy after a median follow-up of 3.5 years. Clinical relapse occurred in 9/33 (27.4%) patients at a median of 34 months after treatment discontinuation. Conclusions: Replacement of oral cyclophosphamide with a single intravenous pulse on months 2, 4 and 6 of the modified Ponticelli regimen can be an effective and safe alternative for treatment of membranous nephropathy.