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Evidence summaries

Immunosuppressive Treatment or Alkylating Agents for Idiopathic Membranous Nephropathy

Immunosuppressive agents or alkylating agents appear to reduce mortality or end-stage kidney disease, and increase remission compared with non-immunosuppressive treatments in idiopathic membranous nephropathy. Level of evidence: "B"

A Cochrane review [Abstract] 1 included 65 studies on immunosuppressive treatments for idiopathic membranous nephropathy (IMN), with a total of 3807 subjects.

Combinedcorticosteroids and alkylating agents reduced death and ESKD, increased complete or partial remission and complete remission (table T1), and decreased the number of patients with doubling of serum creatinine. Immunosuppression significantly reduced all-cause mortality or risk of ESKD and risk of ESKD, increased complete or partial remission (table T2 ), and decreased the number of patients with doubling of serum creatinine. However this regimen was associated with more discontinuations or hospitalisations.

Alkylating agents with or without corticosteroids compared with no treatment or ACEi or corticosteroids monotherapy in adults with idiopathic membranous nephropathy and nephrotic syndrome

Outcome Follow-up: 6 monthsto 12 yearsRelative effect(CI)Control = no treatment or ACEi or corticosteroidsIntervention = Alkylating agents and corticosteroidsNumber of participants (trials)
DeathRR0.76(0.25 to 2.30)37/100028/1000 (9 to 84)440 (7)
End-stage kidney diseaseRR 0.42(0.24 to 0.74)146/100061/1000 (35 to 108)537 (9)
Complete or partial remissionRR 1.37(1.04 to 1.82)411/1000604/1000 (459 to 803)468 (9)

Immunosuppressive treatments compared with placebo or no treatment or ACEi in adults with idiopathic membranous nephropathy and nephrotic syndrome

Outcome Follow-up: 6 months to 12 yearsRelative effect(CI)Control = no treatment or ACEiIntervention = Immunosuppressive treatmentsNumber of participants (trials)
DeathRR 0.73(0.34 to 1.59)40/100030/1000 (14 to 64)944 (16)
End-stage kidney diseaseRR 0.59(0.35 to 0.99)124/100073/1000 (43 to 123)944 (16)
Complete or partial remissionRR 1.44(1.05 to 1.97)337/1000485/1000 (355 to 663)879 (16)

A 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.

Comment: The quality of evidence is downgraded by imprecise results (limited study size for each comparison) .

    References

    • 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.[PubMed]
    • 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. BMJ Open 2019;9(9):e030919. [PubMed]

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