Immunosuppressive Therapy in Primary Membranous Nephropathy with Compromised Renal Function

Abstract

<b><i>Introduction:</i></b> Renal dysfunction at presentation is uncommon in primary membranous nephropathy (PMN). The data on the outcome of PMN patients with renal dysfunction at outset are scarce. The objective of the current study was to report the clinical outcomes of PMN patients with renal dysfunction. <b><i>Material and Methods:</i></b> This prospective longitudinal observational study included PMN patients (both incident and treatment resistant) with an estimated glomerular filtration rate of <60 mL/min/1.73 m<sup>2</sup>. Immunosuppressive treatment was as per the unit’s protocol. Patients were evaluated for proteinuria, creatinine, and serum albumin at monthly intervals for 6 months, then quarterly for a year, and then biannually. Both serum and tissue anti-PLA2R were performed at baseline. Outcome: Percentage of patients achieving clinical remission. <b><i>Results:</i></b> Sixty-four adults met study criteria and were analysed. The median (IQR) age of the patients was 48 (40, 56) years. PMN was PLA2R related in 52 (81.3%) patients. Twenty-eight (43.8%) and 30 (46.9%) patients were in remission at 12 months and at the end of the study [median (IQR) follow up: 24 months (12, 35)], respectively. Eight (12.5%) had progressed to end-stage renal disease at the last follow-up. Median (IQR) baseline anti-PLA2R titre was 150.1 RU/mL (38.5, 308). Nineteen (61.3%) and 18 (58.1%) patients with >90% reduction in anti-PLA2R titres at 12 months were in clinical remission at 12 months and at the end of the follow-up, respectively. Both cyclical cyclophosphamide/steroids (cCYC/GC) and rituximab were equally effective in inducing remission, but rituximab had a favourable adverse event profile compared to cCYC/GC. <b><i>Conclusion:</i></b> To conclude, both cCYC/GC and rituximab are equally effective in inducing remission of nephrotic state with compromised renal function due to PMN. Immunosuppression induces remission in up to 50% PMN patients with CKD-stage 3–4.

Rituximab Dosing in Glomerular Diseases: A Scoping Review

“… 25 , 26 Another PCS included patients receiving 3 different regimens: 4 doses of 375 mg/m 2 /week; 1000 mg as 2 doses 2 weeks apart; and a CD19 targeted treatment approach. 34 The remaining RCT evaluated a single dose of 1000 mg after 6 months of tacrolimus. 21 We did not identify any RCT or PCS examining use of rituximab to maintain remission in MN.…”

Rituximab in patients with membranous nephropathy and kidney insufficiency

“…Cyclical cyclophosphamide plus glucocoticoids is often used in membranous nephropathy patients with kidney insufficiency ( Ramachandran et al, 2016 ; Ramachandran et al, 2022 ), and is also recommended as the first-line agents by the 2021 KDIGO guidelines. However, cyclophosphamide is not widely used in clinical practice among young patients with fertility requirements or patients with poor immunity because of reproductive toxicity and strong immunosuppression.…”

“…At present, RTX is widely used in the treatment of membranous nephropathy, and it is also recommended by the 2021 KDIGO guidelines for the treatment of membranous nephropathy at moderate to high-risk of progressive loss of kidney function ( Rovin et al, 2021 ). However, for patients with membranous nephropathy and kidney insufficiency, whether RTX can effectively decrease proteinuria, preserve renal function, and delay or even reverse the progress of renal failure is still controversial ( Wang et al, 2018 ; Hanset et al, 2020 ; Ramachandran et al, 2022 ).…”

Cyclophosphamide induced early remission and was superior to rituximab in idiopathic membranous nephropathy patients with high anti-PLA2R antibody levels

“…After the exclusion of 107 duplicates and irrelevant studies, 21 potentially eligible studies were further screened. Finally, 8 studies [13][14][15][16][17][18] involving 600 adult patients with IMN were included.…”