Systematic review and network meta-analysis for the 2026 update of the evidence-based clinical practice guidelines for the management with immunosuppressive therapies and biologic agents of membranous nephropathy
In brief
Oral cyclophosphamide reduces kidney failure risk in membranous nephropathy
In a network meta-analysis of 52 trials, oral cyclophosphamide was the only therapy shown to lower the chance of kidney failure, while ACTH, tacrolimus and cyclophosphamide (IV or oral) improved remission rates compared with placebo or standard care. However, most efficacy and safety findings were based on low-certainty evidence, underscoring the need for larger, well-designed trials.
- Journal
- Clinical and experimental nephrology (Q2)
- Published
- 19 September 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Reiji Takami, Hiroki Nishiwaki, Yasushi Tsujimoto, Yuji Oe, Keisuke Onishi, Yuki Oba, et al.
- PMID
- 42762405
- DOI
- 10.1007/s10157-026-02944-4
Why clinicians should know about it
- Picked for Transplantation (top studies of the week, 20 September 2026): Immunosuppression in membranous nephropathy, pre‑transplant disease
- Picked for Nephrology (top studies of the week, 20 September 2026).
Abstract
BACKGROUND: Multiple immunosuppressive therapies are used to induce remission in membranous nephropathy, but differences in study populations, treatment regimens, and outcome definitions complicate comparisons of their relative efficacy and safety. We aimed to synthesize randomized evidence comparing immunosuppressive therapies, including rituximab. METHODS: We conducted a systematic review and network meta-analysis of randomized controlled trials for adult patients with idiopathic membranous nephropathy. Outcomes included mortality, kidney failure, remission of nephrotic syndrome, decline in kidney function, infections, and adverse events. Random-effects network meta-analyses were performed, and the certainty of evidence for each comparison was assessed using the Confidence in Network Meta-Analysis (CINeMA) framework. RESULTS: A total of 52 randomized controlled trials involving multiple immunosuppressive strategies were included. Several treatments, including adrenocorticotropic hormone, tacrolimus, intravenous cyclophosphamide, and oral cyclophosphamide, were associated with higher complete or partial remission rates compared with placebo, standard treatment, or no treatment. Oral cyclophosphamide was also associated with a lower risk of kidney failure in some comparisons, whereas azathioprine, cyclosporine, and glucocorticoids were associated with lower relapse rates. However, the certainty of evidence across most efficacy and safety outcomes was low to very low because of risk of bias, imprecision, heterogeneity, and incoherence. Infection outcomes were inconsistently reported and estimates were generally imprecise. CONCLUSION: Treatment effects differed across interventions, but the overall certainty of the evidence was limited, highlighting the need for well-designed, adequately powered randomized trials with standardized methodologies.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.