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.