A Cochrane review «Immunosuppressive treatment for primary membranous nephropathy in adults with nephrotic syndrome»1 «von Groote TC, Williams G, Au EH et al. Immunosuppressive treatment for primary membranous nephropathy in adults with nephrotic syndrome. Cochrane Database Syst Rev 2021;(11):CD004293. »1 included 65 studies on immunosuppressive treatments for idiopathic membranous nephropathy (IMN), with a total of 3807 subjects.
Combined corticosteroids and alkylating agents reduced death and ESKD, increased complete or partial remission and complete remission (table « Alkylating agents with or without corticosteroids compared with no treatment or ACEi or corticosteroids monotherapy in adults with idiopathic membranous nephropathy and nephrotic syndrome»1), and decreased the number of patients with doubling of serum creatinine. Immunosuppression reduced all-cause mortality or risk of ESKD and risk of ESKD, increased complete or partial remission (table «Immunosuppressive treatments compared with placebo or no treatment or ACEi in adults with idiopathic membranous nephropathy and nephrotic syndrome»2 ), and decreased the number of patients with doubling of serum creatinine. However this regimen was associated with more discontinuations or hospitalisations.
| Outcome Follow-up: 6 months to 12 years | Relative effect (CI) | Control = no treatment or ACEi or corticosteroids | Intervention = Alkylating agents and corticosteroids | Number of participants (trials) |
|---|---|---|---|---|
| Death | RR0.76 (0.25 to 2.30) | 37/1000 | 28/1000 (9 to 84) | 440 (7) |
| End-stage kidney disease | RR 0.42 (0.24 to 0.74) | 146/1000 | 61/1000 (35 to 108) | 537 (9) |
| Complete or partial remission | RR 1.37 (1.04 to 1.82) | 411/1000 | 604/1000 (459 to 803) | 468 (9) |
| Outcome Follow-up: 6 months to 12 years | Relative effect (CI) | Control = no treatment or ACEi | Intervention = Immunosuppressive treatments | Number of participants (trials) |
|---|---|---|---|---|
| Death | RR 0.73 (0.34 to 1.59) | 40/1000 | 30/1000 (14 to 64) | 944 (16) |
| End-stage kidney disease | RR 0.59 (0.35 to 0.99) | 124/1000 | 73/1000 (43 to 123) | 944 (16) |
| Complete or partial remission | RR 1.44 (1.05 to 1.97) | 337/1000 | 485/1000 (355 to 663) | 879 (16) |
A network meta-analysis «Zheng Q, Yang H, Liu W et al. Comparative efficacy of 13 immunosuppressive agents for idiopathic membranous nephropathy in adults with nephrotic syndrome: a systematic review and network meta-analysis»2 included 48 RCTs with 2736 patients and 13 immunosuppressive agents. Most regimens (except for leflunomide, mizoribine and steroids) showed significantly higher probabilities of total remission when compared with non-immunosuppressive therapies (the control group), with risk ratios (RRs) of 2.71 (95% CI) 1.81 to 4.06 for tacrolimus+tripterygium wilfordii, 2.16 (1.27 to 3.69) for adrenocorticotropic hormone, 2.02 (1.64 to 2.49) for tacrolimus, 2.03 (1.13 to3.64) for azathioprine, 1.91 (1.46 to 2.50) for cyclosporine, 1.86 (1.44 to2.42) for mycophenolate mofetil, 1.85 (1.52 to 2.25) for cyclophosphamide, 1.81 (1.10 to 2.98) for rituximab, 1.80 (1.38 to 2.33) for tripterygium wilfordii, 1.72 (1.35 to 2.19) for chlorambucil. The changes of serum creatinine were not significantly different between immunosuppressive agents and the control. Infection, gastrointestinal symptoms, and bone marrow suppression were the common adverse events associated with most of the immunosuppressive therapies.
A multicenter, double-blind, randomized, placebo-controlled trial «Isaka Y, Sakaguchi Y, Shinzawa M, et al. Rituximab for Relapsing Nephrotic Syndrome in Adults: A Randomized Clinical Trial. JAMA 2025;334(22):2011-2019. »3 evaluated the effects of rituximab on relapse (n=72). The relapse-free rate at week 49 was 87.4% (95% CI 69.8% to 95.1%) in the rituximab group and 38.0% (95% CI 22.1% to 53.8%) in the placebo group (P < .001 by 1-sided log-rank test).
Comment: The quality of evidence is downgraded by imprecise results (limited study size for each comparison) .