The long-term prognosis of IgA nephropathy (IgAN) and the optimal target for proteinuria treatment remain controversial. This study, utilizing a large prospective cohort from China, aims to assess the long-term outcomes of IgAN and to explore the definition of proteinuria remission. We enrolled 2 141 patients with biopsy-proven IgAN, all with at least 12 months of follow-up, from a prospective IgAN cohort at Peking University First Hospital. We utilized Kaplan-Meier analysis, Cox regression, and an eGFR slope calculated via a linear mixed model to investigate kidney outcomes. The median (Q1, Q3) baseline proteinuria was 1.26 (0.65, 2.40) g/d, and the estimated GFR was 80 (52, 103) mL/min/1.73m². After a mean follow-up of 5.8 (±4.4) years, 509 (24%) patients progressed to end-stage kidney disease (ESKD). The median kidney survival time was 12.4 years, the annual event rate of ESKD was 41.1 per 1000 person-years, and the 15-year kidney survival rate was 40%. Time-averaged proteinuria level was strongly associated with kidney failure (adjusted HR: 1.76, 95%CI: 1.65 to 1.88). Restriction cubic spline analysis indicated that the risk of ESKD increases rapidly when time-average proteinuria exceeded 0.5 g/d. There was no significant difference in long-term kidney survival between patients with proteinuria < 0.3 g/d and those with 0.3–0.5 g/d, with both groups demonstrating a better prognosis. The long-term outcomes for patients with IgAN under current treatment strategies remain poor, with most progressing to ESKD within 15 years. Patients with time-averaged proteinuria ≥ 0.5 g/d experience worse kidney outcomes, challenging the previous view that proteinuria < 1.0 g/d was associated with a low risk of kidney failure.

Hydroxychloroquine (HCQ), a well-known immunomodulator, has recently been found to be a promising and safe anti-proteinuric agent for treating IgA nephropathy (IgAN). We aimed to compare the efficacy and safety of HCQ and corticosteroid treatment in patients with IgAN. This is a case-control study. Ninety-two patients with IgAN who received HCQ in addition to routine renin-angiotensin-aldosterone system inhibitors (RAASi) therapy were included. Ninety-two matched historical controls who received corticosteroids were selected by propensity score matching. The clinical data over 6 months were compared. Baseline proteinuria levels were comparable between the HCQ and corticosteroid groups (1.7 [1.2, 2.3] vs. 1.8 [1.3, 2.5] g/d, p = 0.96). The percentage reduction in proteinuria at 6 months was smaller in the HCQ group than in the corticosteroid group (− 48.5% [− 62.6, − 31.4] vs. -62.9% [− 81.1, − 34.9], p = 0.006). The time averaged proteinuria within the 6 months of observation was comparable for the HCQ and corticosteroid groups (1.1 [0.8, 1.5] vs. 1.1 [0.5, 1.8] g/d, p = 0.48). The cumulative frequency of patients with a 50% reduction in proteinuria during the study was also comparable between the two groups (52.2% vs. 62.0%, p = 0.25). However, six of the 92 (6.5%) patients suffered from severe adverse events (SAEs) in the corticosteroid group, while no SAEs were observed in the HCQ group (6.5% vs. 0%, p = 0.03). The antiproteinuric effect of HCQ might be slightly inferior to that of corticosteroids over 6 months in patients with IgAN who were deemed to be candidates for HCQ and not corticosteroids treatment. However, HCQ treatment was safer than corticosteroid treatment.

Introduction: IgA nephropathy (IgAN) is the most prevalent primary glomerulonephritis globally. While nephrotic syndrome (NS) is uncommon in IgAN, its significance remains unclear.Methods: We conducted a retrospective analysis of 170 IgAN patients, classifying them into NS (n = 85) and non-NS (n = 85) groups. Our study aims to compare their clinical characteristics, treatment responses, and prognoses. Patients were selected based on renal biopsy from 2003 to 2020. Propensity score matching ensured comparability. Clinical, pathological, and immunological data were analyzed. Composite endpoints were defined as end-stage kidney disease (ESKD) or a 30% decline in estimated glomerular filtration rate (eGFR).Results: NS patients showed higher eGFR (74.3 ± 36.8 vs. 61.5 ± 33.6 mL/min.1.73 m², p = 0.02), severe hematuria (35.0 (4.7,147.5) vs. 4.0 (1.8,45,0) cells/μl, p < 0.001), severe foot process effacement (p = 0.01), and lower C3 levels (1.0 ± 0.3 vs. 1.1 ± 0.2 g/L, p = 0.03). In contrast, the non-NS group had higher BMI (24.3 ± 4.0 vs. 26.8 ± 3.7 kg/m², p < 0.001) and elevated serum uric acid levels (376 (316,417) vs. 400 (362, 501) mmol/L, p = 0.001), suggesting metabolic factors might contribute to their condition. Both groups exhibited similar MESTC scores. NS patients had higher complete remission rates (26.2% vs. 14.1%, p = 0.04). Cox regression revealed NS independently associated with a higher risk of composite endpoints (HR = 1.97, 95% CI 1.05–3.72, p = 0.04). Linear mixed models did not show significant eGFR trajectory differences.Discussion: This study has established that IgAN patients with NS exhibit distinct characteristics, including active disease and increased complement activation. NS is independently associated with a poorer prognosis, emphasizing the need for targeted interventions in this subgroup.

Background: The International IgA Nephropathy Prediction Tools using clinical variables and the Oxford MEST scores were developed in outdated cohorts. External validation is required to assess the tool's applicability in predicting progression risk for patients on novel therapies. Methods: We included 677 immunoglobulin A nephropathy (IgAN) patients (Peking University First Hospital, 2003–23) treated with endothelin receptor antagonists, Nefecon, sodium-glucose cotransporter 2 inhibitors, hydroxychloroquine or telitacicept, a BAFF/APRIL inhibitor. The primary outcome was defined as a 50% decline in estimated glomerular filtration rate or end-stage kidney disease. Discrimination (C-statistic), calibration [calibration slope, Integrated Calibration Index (ICI)], model fit (R2D) and risk stratification (Kaplan–Meier curves) were assessed. Results: The median follow-up was 4.8 years (interquartile range 2.2, 8.1), and 190 (28.1%) patients experienced the primary outcome, with a 5-year risk of 9.8%. Compared with the median biopsy year of reported cohorts of original model, our cohort is more contemporary (2017). We validated both original and updated models (and for full model with and without race version). All versions showed adequate discrimination, poor calibration and model fit: C-statistic ∼0.74, calibration slope ∼0.50, R2D 0.10, and poor separation of Kaplan–Meier curves, except for the highest-risk group. The tools consistently overestimated risk in patients receiving novel therapies. These findings further demonstrated that novel therapies can improved clinical outcomes for IgAN patients. Conclusions: In this study, both versions of both models demonstrated limited performance and overestimated risks. Given the prognostic improvement with novel IgAN therapies, these prediction tools may need updating for use in currently treated patients.

Introduction: The post-biopsy International IgA Nephropathy Prediction Tool (IIgAN-PT) models were updated to assess progression risk 1 or 2 years after biopsy. This study externally validated both models in a contemporary Asian cohort with extended follow-up to evaluate long-term predictive performance. Methods: We included 1,296 Chinese patients with biopsy-proven IgAN. The primary outcome was a composite of end-stage kidney disease or a 50% decline in estimated glomerular filtration rate (eGFR) within 1 year post-biopsy. Model performance was evaluated using the coefficient of determination (R2) and Akaike information criterion to assess model fit, concordance statistics (C-statistics) and Kaplan-Meier survival curves for discrimination, and the integrated calibration index (ICI) for calibration. Further analysis included net reclassification improvement (NRI), integrated discrimination improvement (IDI), and decision curve analysis. Results: Over a median follow-up of 4.5 years (IQR: 2.2–7.6), 20.2% of patients experienced the primary outcome. Models with and without race demonstrated excellent performance, with R2 of 81.0% and 80.2%. C-statistics for 4- and 5-year risk prediction were 0.89 and 0.87, respectively. Kaplan-Meier curves showed clear separation between risk strata, especially in the highest-risk group, who had lower baseline eGFR and a steeper decline. Calibration was good for both 4- and 5-year predictions as reflected by the ICI. Nonetheless, both models underestimated risk in the highest-risk group at these time points. Discrepancies became more apparent beyond 10 years, as confirmed by DCA. Compared to the original models, the updated models improved risk reclassification, as indicated by both NRI and IDI for 4- and 5-year risk prediction. Conclusion: The post-biopsy IIgAN-PT models demonstrated good predictive performance and may support individualized risk stratification and treatment decisions in IgAN.

Relapse in IgA nephropathy (IgAN) remains under-researched. This study investigates the incidence of IgAN relapse, its association with adverse outcomes, and its risk factors within a prospective cohort. Prospective cohort study. The study included 1,069 patients with IgAN who achieved remission following treatment. Relapse or not after remission of IgAN. The first occurrence of either end-stage kidney disease (estimated glomerular filtration rate [eGFR] <15 mL/min/1.73 m², dialysis, or kidney transplantation) or a 50% decline in eGFR. We assessed relapse incidence, its correlation with kidney endpoint events, and identified clinicopathological predictors of relapse using Cox regression analysis. Least Absolute Shrinkage and Selection Operator Cox regression was performed to screen predictive variables to predict relapse. Among the 1,069 patients, 348 (33%) experienced 411 relapses. The overall relapse-free rates at 1, 5, and 10 years were 93%, 65%, and 48%, respectively. Relapse patients had a significantly higher incidence kidney endpoint events compared with nonrelapse patients. The relapse group also exhibited a more rapid decline in eGFR compared with the nonrelapse group (-2.3 vs -1.0 mL/min/1.73 m²/year). Patients with corticosteroid-induced remission had a higher likelihood of relapse within 3 years. Controlling 24-hour urinary protein at remission to below 0.3 g/d was associated with a significantly improved relapse-free rate. Single-center study; no standardized definition for IgAN remission and relapse. Relapse is prevalent in IgAN and is associated with an increased rate of kidney endpoint events and accelerated eGFR decline. Predictors of relapse encompass various clinicopathological indicators and medications, with stricter control of proteinuria at remission being crucial for reducing relapse rates.