Substitution of Oral for Intravenous Cyclophosphamide in Membranous Nephropathy

Abstract

BackgroundOptimal 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 patients who are high risk. 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.MethodsIn 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).ResultsAt 24 months, 39 (71%) patients achieved clinical response with complete remission observed in 23 patients (42%) and partial remission in 16 (29%). 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%), five of whom started chronic RRT after a median follow-up of 3.5 years. Clinical relapse occurred in nine of 33 (27%) patients at a median of 34 months after treatment discontinuation.ConclusionsReplacement 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.PodcastThis article contains a podcast at https://www.asn-online.org/media/podcast/K360/2020_09_24_KID0002802020.mp3

Predictive value of the domain specific PLA2R antibodies for clinical remission in patients with primary membranous nephropathy: A retrospective study

“…A retrospective analysis of 32 cases with PMN treated with intravenous CTX (500–750 mg/m2 every month for 6 months) plus steroids reported that 81% of the patients achieved clinical remission [ 25 ]. A long-term observational study of 55 PMN patients found that 70.9% of patients achieved clinical response with CTX regimen [ 26 ]. Another retrospective analysis studied 40 patients treated with intravenous CTX (600 mg/m2 every 4 weeks for up to 6 months) plus steroids.…”

A case report of breast cancer and membranous nephropathy with positive anti phospholipase A2 receptor antibodies

“…The cyclophosphamide dose used to treat the breast cancer was a lower dose than that used to successfully treat primary MN; however the contribution of this treatment to the resolution of her nephrosis cannot be completely excluded, indeed there are reports of partial remission of MN with Cyclophosphamide doses of less than 3 g [ 4 ]. Although less likely given her high PLA2R titre, a spontaneous remission of primary MN is also possible independent of the malignancy.…”

The efficacy and safety of Sanqi Qushi Granule in patients with idiopathic membranous nephropathy ——protocol of a multicenter, randomized control trial (SQ-AUTUMN)

“…The TR rate of immunosuppressive therapy reported by different studies is inconsistent. To estimate the pooled TR rate of the control group, we conducted fixed-effects meta-analyses among data from five studies [ 20 – 24 ] by using the R software (version 4.0.2) plugin metaprop function. After calculation, the pooled TR rate of cyclical CTX/steroids regime is 56%(95%CI, 50.7–61.4) with a low heterogeneity (I 2 = 0.000%, P < 0.000).…”