Gut microbiota transplantation has been reported to improve the renal function of membranous nephropathy (MN). However, whether there is a causal effect of gut microbiota on MN remained unclear. We performed two-sample Mendelian randomization (MR) analysis. The inverse variance weighted (IVW) method was used as the main approach to evaluate the causal relationship between gut microbiota and MN. Additional methods including MR-Egger regression, weighted median, and MR-weighted mode were also conducted. Cochrane’s Q test, MR-Egger regression, and MR-PRESSO were employed to detect heterogeneity and pleiotropy, respectively. A total of 196 gut microbiota were examined. After IVW and sensitivity analysis, eight gut bacteria taxa were observed causal effects on the risk of MN. Specifically, Genus. Oscillibacter was a protective factor (OR: 0.57; 95%CI: 0.328-0.979; P = 0.042), while Class. Melainabacteria (OR: 1.51; 95% CI: 1.004-2.277; P = 0.048), Genus. Butyricicoccus (OR: 2.16; 95% CI: 1.005-4.621; P = 0.048), Genus. Catenibacterium (OR: 1.49; 95% CI: 1.043-2.134; P = 0.028), Genus.Ruminiclostridium5 (OR: 1.74; 95% CI: 1.053-2.862; P = 0.030), Genus. Ruminococcaceae UCG-003 (OR: 1.73; 95% CI: 1.110-2.692; P = 0.015), Order. Bacillales (OR: 1.52; 95% CI:1.135-2.025; P = 0.0048) and Order. Gastranaerophilales (OR: 1.45; 95% CI: 1.010-2.085; P = 0.044) were risk factors. Heterogeneity was not significant for most single-nucleotide polymorphisms, and no statistical difference in pleiotropy. This study first indicated the causal association between specific gut microbiota and MN, which would be of great significance to guide clinical prevention and treatment in MN.

Abstract Objective: This study was to evaluate the efficacy of rituximab (RTX) versus conventional agents and different RTX dose regimens in the treatment of idiopathic membranous nephropathy (IMN). Methods: After systematically searched associated studies up to 1st December 2020, we performed a fixed and random-effects meta-analysis using the Stata software and evaluated the quality of included studies by the risk of bias scale of the Cochrane collaboration tool. Results: RTX had a higher total remission (TR) (OR = 2.663, 95% CI 1.361 to 5.210, P = 0.004) than conventional therapy for patients at moderate risk for lose of kidney function (pre-study proteinuria < 8 g/d), however, for patients at severe risk (pre-study proteinuria > 8 g/d), there was no significant difference in TR (OR = 0.691, 95% CI 0.064 to 7.423, P = 0.761). In RTX dose studies, standard dose regimen had a better effect of reducing proteinuria than low-dose regimen (Low dose MD = -3.999, 95% CI -6.177 to -1.820; standard dose MD = -5.220, 95% CI -7.160 to -3.279, P < 0.0001). Significant improvement in serum albumin was seen in patients treated with standard dose than low dose regimen (Low dose MD = 0.601, 95% CI 0.052 to 1.150, P = 0.032; standard dose MD = 0.963, 95% CI 0.740 to 1.185, P < 0.0001). Conclusion: For patients with moderate risk IMN, RTX treatment has a higher TR than conventional therapy. Standard dose RTX is more effective than low dose in reducing proteinuria and recovering serum albumin levels.