Background: Recently, a few studies have indicated a relationship between the gut microbiota and IgA nephropathy (IgAN). Whether the gut microbiota participates in the pathogenesis of IgAN and whether probiotics are effective in treating IgAN are still controversial. Therefore, this study aimed to identify the differences in the structure of the gut microbiota between IgAN and controls and to evaluate the efficacy and mechanism of probiotics in the treatment of IgAN. Methods: To address this question, 35 IgAN patients and 25 healthy volunteers were enrolled, and a mouse IgAN model was also constructed. The stool microbes were analyzed by 16S rRNA high-throughput sequencing to identify the differential strains between IgAN and healthy controls. The impact of probiotics on the structure of the intestinal flora and the efficacy of the probiotics in the treatment of IgAN were evaluated. Results: Although the microflora structure of mice and humans was not the same, both patients and mice with IgAN exhibited gut microbiota dysbiosis, with all subjects presenting an evident decrease in Bifidobacterium levels. The Bifidobacterium proportion was negatively correlated with proteinuria and hematuria levels, indicating that the decreased Bifidobacterium abundance could be related to IgAN severity. Probiotic treatment containing Bifidobacterium in IgAN mice could significantly alleviate gut dysbiosis, specifically by increasing the proportion of beneficial bacteria and reducing the abundance of potentially pathogenic bacteria. Moreover, both probiotics and their metabolites, short-chain fatty acids (SCFAs), could attenuate IgAN clinicopathological manifestations by inhibiting the NLRP3/ASC/Caspase 1 signaling pathway. Conclusions: Supplementation with probiotics mainly containing Bifidobacterium could markedly improve gut dysbiosis in IgAN. Moreover, both probiotics and their SCFA metabolites could attenuate the clinicopathological manifestations of IgAN by inhibiting the NLRP3/ASC/Caspase 1 signaling pathway. Therefore, probiotics have potential as an adjunctive therapy for IgAN.

Background: The triglyceride–glucose (TyG) index is a simple, novel and reliable surrogate marker of insulin resistance. However, evidence for the prognostic impact of an elevated TyG index on IgA nephropathy (IgAN) is limited. Therefore, we evaluated the relationship between the TyG index and the risk of renal progression in IgAN. Method: This cohort study involved biopsy-proven IgAN between January 2009 and December 2018 in West China Hospital, in which patients were assigned to two groups based on the cut-off value of TyG using receiver operating characteristic (ROC) curves. A 1:1 matched-pair analysis was established to optimize the bias in IgAN by propensity score matching (PSM). The TyG index was calculated as ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. The composite endpoint was defined by eGFR decreased ≥50% of the baseline level, end-stage kidney disease (ESKD), renal transplantation and/or death. Univariable and multivariable Cox proportional hazard models were applied to confirm the predictive value of the optimal marker. Results: Before PSM, a total of 1210 participants were ultimately included. During a median follow-up period of 55.8 months (range 37.20–79.09 months), 129 participants progressed to the composite endpoint (10.7%). After PSM, 366 patients were enrolled in the matched cohort, of whom 34 (9.3%) patients reached the endpoints. Based on the cut-off value of the TyG index, patients were divided into the low TyG index group (TyG ≤ 8.72, n = 690) and the high TyG index group (TyG > 8.72, n = 520). Further analysis demonstrated that a higher TyG index was significantly associated with a higher risk of reaching composite endpoints in IgAN patients in both the unmatched and matched cohorts (before PSM: HR 2.509, 95% CI 1.396–4.511, p = 0.002; after PSM: HR 2.654, 95% CI 1.299–5.423, p = 0.007). Conclusion: A high TyG index is associated with a higher risk of renal progression.

Background: The red blood cell distribution width-to-albumin ratio (RAR) is a novel composite biomarker that integrates hematological, inflammatory, and nutritional information, but its association with renal outcomes in immunoglobulin A nephropathy (IgAN) remains unclear. This study aimed to evaluate the association between RAR and long-term renal outcomes in patients with biopsy-proven IgAN. Methods: This study was a retrospective analysis of an established observational cohort, including 1169 patients with biopsy-proven IgAN. RAR was analyzed both categorically, using a receiver operating characteristic (ROC)-derived cutoff, and continuously. Propensity score matching (PSM) was performed at a 1:1 ratio. Kaplan–Meier analysis and multivariable Cox proportional hazards models were used to evaluate the association between RAR and the composite renal endpoint. Restricted cubic spline (RCS) analysis was used to assess the shape of the association. Results: Before PSM, higher RAR was independently associated with the composite renal endpoint in the fully adjusted model (HR 1.880, 95% CI 1.222–2.893; p = 0.004). The association remained significant after PSM (HR 2.128, 95% CI 1.067–4.243; p = 0.032). When analyzed continuously, RAR was associated with a higher risk of the composite endpoint before PSM (HR 1.371, 95% CI 1.099–1.711; p = 0.005) and after PSM (HR 1.989, 95% CI 1.199–3.299; p = 0.008). RCS analyses showed significant overall associations before and after PSM, without significant evidence of nonlinearity. Conclusions: Higher RAR was independently associated with adverse renal outcomes in patients with IgAN. Further external validation and large multicenter prospective studies are needed to determine its clinical value.