IgA腎症

BACKGROUND: Recurrent immunoglobulin A nephropathy after kidney transplantation remains a major clinical challenge, but risk factors are not fully defined. This study aimed to evaluate the incidence of biopsy-proven recurrent IgAN and identify risk factors for recurrence in a contemporary Scandinavian cohort. METHODS: We conducted a multicenter cohort study including adult patients with biopsy-proven immunoglobulin A nephropathy who received a first kidney-only transplantation between 1990 and 2020 across two Danish transplantation centers. Recurrence incidence and associations with clinical and donor-related characteristics were assessed during follow-up. RESULTS: A total of 118 recipients were followed for a median of 5.5 years. Biopsy-confirmed recurrence occurred in 14% of patients, corresponding to a cumulative incidence of 16% at 10 years post-transplantation. Younger age at immunoglobulin A nephropathy diagnosis, faster progression to kidney failure, and receipt of a kidney from a living or genetically related donor were independently associated with an increased risk of recurrence. Maintenance post-transplant steroid use was not associated with recurrence. Recurrent immunoglobulin A nephropathy was associated with an increased risk of graft failure compared with non-recurrent disease (unadjusted HR 3.8; adjusted HR 6.7). CONCLUSIONS: Recurrence of IgAN after kidney transplantation remains a clinically significant challenge, associated with younger age, rapid progression to KF, and transplantation from living or genetically related donors. Maintenance post-transplant steroid use was not associated with recurrence risk in this cohort. Larger and more diverse cohorts are warranted to clarify donor-related risk, strengthen the evidence on immunosuppressive protocols and guide strategies to improve graft outcomes.

BACKGROUND: IgA nephropathy (IgAN) is an immune-inflammatory glomerulonephritis mediated by both genetic and environmental factors. Recent research indicates a close association between gut microbiota dysbiosis and IgAN development. Additionally, circulating inflammatory proteins also play a significant role in the progression of IgAN. However, the causal relationship among gut microbiota, circulating inflammatory proteins, and IgAN remains unclear. METHODS: This study utilized publicly available Genome-Wide Association Study (GWAS) data for Mendelian randomization (MR) analysis to investigate the causal relationship among gut microbiota, circulating inflammatory proteins, and IgAN, as well as to examine the mediating role of circulating inflammatory proteins in the association between gut microbiota and IgAN. The primary analytical method employed in this study was Inverse Variance Weighted (IVW) analysis with specific attention given to Bayesian Weighted MR results and supported by MR-Egger regression, Weighted Median Model (WME), median model, and Simple Model (SM) approaches. Several sensitivity analyses were performed to evaluate the robustness of MR analysis findings. RESULTS: (1) MR analysis of gut microbiota and IgAN indicates negative associations between g_Roseburia, g_Faecalibacterium, s_Odoribacter_splanchnicus, and s_Roseburia_unclassified with IgAN risk, while positive associations exist between s_Paraprevotella_unclassified and s_Lachnospiraceae_bacterium_7_1_58FAA with IgAN risk. (2) Circulating inflammatory proteins to IgAN in MR analysis showed that IL-10RA was negatively correlated with the risk of IgAN, while TSGP-CD5, FGF23, LIF, and TGF-α levels were positively correlated with the risk of IgAN. (3) Mediation analysis suggests that TGF-α serves as a mediator between s_Odoribacter_splanchnicus and the causality of IgAN. (4) The results of the reverse MR analysis suggest no significant causal effect of IgAN on gut flora and circulating inflammatory proteins. Sensitivity analyses consistently support the reliability of the study results. CONCLUSION: Our research findings, obtained through genetic methods, substantiate the causal link between gut microbiota, circulating inflammatory proteins, and IgAN. The identification of biomarkers offers novel insights into the potential mechanisms underlying IgAN, which can be advantageous for early diagnosis and the development of more effective treatment strategies.

INTRODUCTION: Hematuria is a hallmark feature of IgA nephropathy (IgAN); however, its long-term impact on kidney outcomes remains incompletely characterized because of time-dependent confounding and lack of a standardized cutoff. This study evaluated the longitudinal association between hematuria and kidney disease progression. METHODS: We included 1771 participants with biopsy-proven IgAN. Hematuria was categorized into the following 4 groups: < 10, 10 to < 20, 20 to < 100, and ≥ 100 red blood cells (RBC)/μl. The primary outcome was a composite kidney outcome (40% estimated glomerular filtration rate [eGFR] decline or kidney failure). Conventional Cox proportional hazards models were used to assess baseline hematuria, whereas marginal structural models (MSMs) were employed to evaluate time-updated hematuria, accounting for time-dependent confounders and fluctuations in clinical parameters. RESULTS: During a median follow-up of 48 months, the primary outcome occurred in 487 (27.5%) participants. In the fully adjusted baseline Cox model, baseline hematuria was not significantly associated with the primary outcome. In contrast, MSMs revealed that time-updated hematuria ≥ 100 RBC/μl was significantly associated with an increased risk of progression (hazard ratio [HR]: 1.53; 95% confidence interval [CI]: 1.14-2.06). The adverse impact was particularly pronounced in subgroups with a baseline eGFR < 60 ml/min per 1.73 m2 and those with baseline proteinuria ≥ 0.5 g/d. Even moderate time-updated hematuria (20 to < 100 RBC/μl) was correlated with a substantially elevated risk (HR: 1.89; 95% CI: 1.33-2.72) in the subgroup with eGFR <60 ml/min per 1.73 m2. CONCLUSION: Our findings suggest that persistent hematuria ≥ 100 RBC/μl may serve as a valuable risk stratification standard, particularly given the significantly magnified risk in patients with pre-existing renal impairment or uncontrolled proteinuria.

Significant advances have been made in elucidating the role of non-steroidal mineralocorticoid receptor antagonists (ns-MRAs) in non-diabetic kidney disease (NDKD). As a key downstream effector of the renin-angiotensin system (RAS), pathological overactivation of the mineralocorticoid receptor (MR) amplifies inflammatory and fibrotic signaling, thereby contributing to proteinuria, podocyte injury, and progressive damage to both the glomerular and tubulointerstitial compartments. Mechanistic studies suggest that ns-MRAs exert multi-level protective effects by targeting the inflammation-fibrosis axis, including preservation of podocyte structure and function, attenuation of acute kidney injury-to-chronic kidney disease transition, improvement of endothelial dysfunction, and suppression of cardiac and renal fibrosis. Clinically, the phase III FIND-CKD trial has provided direct randomized evidence that finerenone slows estimated glomerular filtration rate (eGFR) decline in adults with proteinuric CKD without diabetes, while a prespecified exploratory analysis further supports its potential relevance in glomerular diseases. Real-world studies in IgA nephropathy and membranous nephropathy also suggest antiproteinuric effects when finerenone is added to renin-angiotensin system inhibition. Moreover, co-administration with sodium-glucose cotransporter 2 (SGLT2) inhibitors may confer complementary antiproteinuric effects, although hyperkalemia remains an important safety consideration requiring appropriate monitoring. Collectively, current randomized and observational evidence supports consideration of ns-MRAs in selected patients with proteinuric NDKD, while highlighting the need for subtype-specific interpretation, serum potassium monitoring, and precision-stratified treatment strategies.

Diabetes is often assumed to cause chronic kidney disease (CKD) in patients with diabetes, though non-diabetic pathology may coexist. We reviewed 84 patients with diabetes who underwent native kidney biopsy (2017-2023). Indications included active urinary sediment, nephrotic-range proteinuria and rapid renal decline. Non-diabetic pathology was found in 49% and mixed lesions in 21%, mainly IgA nephropathy, acute tubular necrosis and interstitial nephritis. Biopsy altered management in 23% of cases. These findings support the value of biopsy in patients with diabetes.