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Background: Patients with IgA nephropathy and severe proteinuria have a high lifetime risk of kidney failure. The efficacy and safety of the selective endothelin type A receptor antagonist atrasentan in reducing proteinuria in patients with IgA nephropathy are incompletely understood., Methods: We are conducting a phase 3, multinational, double-blind, randomized, controlled trial involving adults with biopsy-proven IgA nephropathy, a total urinary protein excretion of at least 1 g per day, and an estimated glomerular filtration rate of at least 30 ml per minute per 1.73 m 2 of body-surface area. Patients were randomly assigned to receive atrasentan (0.75 mg per day) or matched placebo for 132 weeks. The primary outcome, assessed at a prespecified interim analysis of data from the first 270 patients in the main stratum, was the change in the 24-hour urinary protein-to-creatinine ratio from baseline to week 36; the change was estimated with the use of a repeated-measures model. (An exploratory stratum of patients who were receiving a sodium-glucose cotransporter 2 inhibitor were included in a separate analysis.) Safety analyses were based on adverse events across the entire main stratum., Results: A total of 340 patients were recruited into the main stratum. Among the first 270 patients in the main stratum (135 per trial group) who completed the week 36 visit, the geometric mean percentage change in the urinary protein-to-creatinine ratio relative to baseline was significantly greater with atrasentan (-38.1%) than with placebo (-3.1%), with a geometric mean between-group difference of -36.1 percentage points (95% confidence interval, -44.6 to -26.4; P<0.001). The percentage of patients with adverse events did not differ substantially between the two groups. Fluid retention was reported by 19 of 169 patients (11.2%) in the atrasentan group and in 14 of 170 (8.2%) in the placebo group but did not lead to discontinuation of the trial regimen. No apparent cases of cardiac failure or severe edema occurred., Conclusions: In this prespecified interim analysis, atrasentan resulted in a significant and clinically meaningful reduction in proteinuria as compared with placebo in patients with IgA nephropathy. (Funded by Novartis; ALIGN ClinicalTrials.gov number, NCT04573478.)., (Copyright © 2024 Massachusetts Medical Society.)

Objectives: IgA vasculitis (IgAV) in adults has been relatively under-investigated. Since outcomes are worse in other forms of vasculitis with increasing age, we investigated the outcomes of IgAV comparing younger adults (18-34), middle-aged adults (35-64) and elderly patients (≥64 years) focusing on kidney outcomes., Methods: We identified patients with renal biopsy-confirmed IgAV nephritis and collected data regarding clinical features and progression to end stage kidney disease (ESKD). The relationship between patient factors and ESKD was analysed by regression., Results: We identified 202 cases, 34% aged 18-34, 43% aged 35-64 and 23% elderly (>64 years). Median follow-up was 44 months. Elderly patients were more likely to present with ESKD (23.9%) compared with middle-aged (13.7%) and younger adults (2.9%) (χ2 11.6, P = 0.002). In patients with independent kidney function at biopsy, there was no difference in outcomes between age groups. Male gender, Black ethnicity, diabetes, histological evidence of chronic renal damage and estimated glomerular filtration rate < 30 ml/min were risk factors for development of ESKD. In this observational study 68.3% of patients received glucocorticoids and 56.9% additional immunosuppression., Conclusion: Elderly patients with IgAV are more likely to have ESKD at presentation, but there is no difference in renal survival between age groups, among those presenting with independent renal function. Renal impairment at biopsy is an independent risk factor for subsequent development of ESKD. There is significant variability in the timing of kidney biopsy and management of these patients among specialist centres. Young adults have outcomes more in keeping with childhood IgAV., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Dense deposit disease (DDD) is a rare renal disorder major affecting adolescents and children, characterized by an absence of distinctive clinical symptoms. Its coexistence with other renal conditions complicates both diagnosis and treatment in clinical practice., Case Presentation: We described a 15-year-old male adolescent presenting with nephrotic syndrome as the initial manifestation, with urinalysis indicating significantly elevated protein and erythrocytes. Unexpectedly, the renal pathological biopsy of the patient exhibited strong positivity for both IgA and C3, characterized by petaloid deposition of C3 along glomerular capillary loops and the glomerular mesangial region, as well as linear deposition in Bowman's capsule and portions of the renal tubular basement membrane. Consequently, the patient was diagnosed with both DDD and IgA nephropathy. The presence of both in a single patient may result in more intricate pathogenic pathways., Conclusions: This specific case elucidates the pathological characteristics of both diseases while investigating the intricate connections and lesion correlations that may occur between them, offering novel insights into their pathogenesis., Competing Interests: Declarations. Ethics approval and consent to participate: All procedures were performed in accordance to the tenets of the Declaration of Helsinki and the study was approved by the Ethics Committee of Fujian Provincial Hospital, Fuzhou, China. All participants involved in the present study provided written informed consent. Consent for publication: Written informed consent for publication this study was obtained from the patients and their guardians. A copy of those written consents is available for review by the Editor-in-Chief of this journal. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: IgA nephropathy (IgAN) is the most common primary glomerulonephritis in the world and is an important cause of chronic kidney disease (CKD) and kidney failure. Outcomes are heterogeneous, and accurate risk stratification is important to identify the highest risk individuals for treatment and to help prevent disease progression. The Oxford classification (OC) is an internationally adopted standard for renal biopsy reporting in IgAN, which measures the degree of histological abnormalities and predicts prognosis. The kidney failure risk equation (KFRE) was developed to predict kidney failure in all causes of CKD and has been shown to be highly accurate across diverse etiologies. This review aimed to compare the KFRE with formulae incorporating the OC in accurately determining the risk of kidney failure in IgAN., Methods: A systematic review was conducted in accordance with the Cochrane library guidelines and PRISMA statement for reporting of systematic reviews. Studies comparing the accuracy of the KFRE with the OC in predicting disease progression and kidney failure in IgAN were evaluated. The search strategy and analysis were performed independently by two reviewers. Studies that were eligible for inclusion compared the KFRE with any tool incorporating the OC in a cohort of individuals with IgAN. Eligible outcomes were reduction of estimated glomerular filtration rate (eGFR) or end-stage renal disease (ESRD), and prognostic tools were required to assess the accuracy of these formulae by discrimination and/or calibration., Results: After searching several databases, only one study was eligible for inclusion in the review. This study of 2300 Chinese individuals with IgAN had a median follow-up of 2.5 years. Two-hundred eighty-eight individuals had a composite outcome of 50% decline in eGFR or ESRD, and 214 individuals developed ESRD. Both the KFRE and the IgAN Risk Prediction (IRP) tool (incorporating the OC) were highly accurate at predicting ESRD with a C-statistic of 0.90 and 0.91, respectively. Subgroup analysis demonstrated improved performance of IRP over KFRE in discrimination for individuals with preserved eGFR (> 60 ml/min/1.73 m 2 ) at baseline. The risk of bias was high due to insufficient follow-up and handling of missing data, so overall confidence in findings is very low., Conclusion: There is currently insufficient evidence to compare the accuracy of the KFRE and OC in determining outcomes in IgAN. Further research is required in this field., Systematic Review Registration: PROSPERO CRD42022364569., Competing Interests: Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare that they have no competing interests., (© 2025. The Author(s).)

Background: The factors influencing diffuse crescentic glomerulonephritis renal survival and prognosis remain uncertain. Additionally, there's no literature on the clinical outcomes of IgA nephropathy, lupus nephritis, and IgA vasculitis nephritis in type II patients., Methods: This study retrospectively examined 107 patients diagnosed with diffuse crescentic glomerulonephritis through biopsy. Analytical methods included Cox regression models and Kaplan-Meier survival analysis to assess the data., Results: Among the 107 enrolled patients, 12 patients had Type I diffuse crescentic glomerulonephritis, 70 patients had Type II, and 25 patients had Type III. The respective 5-year kidney survival rates were 0%, 57.5%, and 18.6% for type I, type II, and type III. Furthermore, among Type II patients, IgA nephropathy emerged as the most prevalent condition. The cumulative 5-year kidney survival rates were 50% for patients with IgA nephropathy, 64% for lupus nephritis, and 70% for Henoch-Schönlein purpura nephritis. A significant association between the risk of ESKD development and several factors was revealed by a multivariate Cox regression analysis: estimated glomerular filtration rate (P = 0.004), initial kidney replacement therapy (KRT) at presentation (P = 0.002), global glomerulosclerosis (P<0.001)., Conclusions: Type II diffuse crescentic glomerulonephritis was the most prevalent type in DCGN, and favors better renal prognosis than type I and III DCGN, in which IgA nephropathy was the most common entity of Type II DCGN. Additionally, estimated glomerular filtration rate, initial KRT at presentation and global glomerulosclerosis were identified as predictors of renal outcomes in diffuse crescentic glomerulonephritis., Competing Interests: Declarations. Ethics approval and consent to participate: All procedures in this study were performed in accordance with the ethical standards of the relevant institutional and/or national research committees, adhering to the principles outlined in the Declaration of Helsinki. The study was approved by the Ethics Committee of Sichuan Provincial People’s Hospital (Ethical approval number: 2024 − 617). We confirm that informed consent to participate was obtained from the parents or legal guardians of all participants under the age of 16, as well as from all adult participants. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Nephrotic syndrome (NS) occurs in 5-15% of patients with IgA nephropathy (IgAN), resulting in poorer long-term outcomes compared to those without NS. Clinical features and renal prognosis for patients with both NS and IgAN across different kidney pathologies have not been fully elucidated. This study included patients with primary IgAN through renal biopsy at the First Affiliated Hospital of Sun Yat-sen University from January 2001 to November 2021 presenting with NS. Renal endpoint was defined as a 50% decrease in estimated glomerular filtration rate or progression to end-stage renal disease. A total of 207 patients with IgAN and NS were categorized into four pathological groups: IgAN with mesangial proliferative glomerulonephritis (IgAN-MsPGN) (n = 150), IgAN with minimal change disease (IgAN-MCD) (n = 49), IgAN with membranous nephropathy (IgAN-MN) (n = 7), and IgAN with membranoproliferative glomerulonephritis (IgAN-MPGN) (n = 1). Compared to the IgAN-MsPGN group, the IgAN-MCD group consisted of more males, had a younger average age, lower blood pressure, a lower prevalence of hematuria, and lower serum albumin and creatinine levels, whereas the IgAN-MN group was characterized by an older average age and lower serum creatinine levels. The IgAN-MCD group exhibited the mildest pathological changes among the groups. Of all patients, 133 were followed for an average follow-up period of 52.07 ± 44.04 months. Thirty-seven patients (27.8%) reached the renal endpoint. The IgAN-MCD group showed a higher rate of proteinuria remission and a better renal prognosis than the IgAN-MsPGN group. In conclusions, significant differences in clinicopathological features and long-term prognosis were observed among NS-IgAN patients with varying pathological phenotypes., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics approval and informed consent statement: All experiments on human subjects were conducted per the Declaration of Helsinki. This study was approved by the ethical committee for clinical research and animals of the First Affiliated Hospital of Sun Yat-sen University, and informed consent was obtained from all subjects., (© 2025. The Author(s).)

Introduction: The efficacy of telitacicept treatment in reducing proteinuria in patients with IgA nephropathy (IgAN) was indicated in a phase II clinical trial with small sample size. In this study, we conducted a large multicenter retrospective study to explore the efficacy and safety of telitacicept in patients with IgAN., Methods: This study recruited patients with IgAN from 19 sites from China who were treated with telitacicept and had been followed up at least once or with side effect reported, since April 1, 2021, to April 1, 2023. The primary outcomes of the study were the changing in proteinuria and eGFR over time., Results: A cohort of 97 patients with IgAN who were treated with telitacicept were recruited, with a median follow-up duration of 3 months. The median baseline proteinuria was 2.3 [1.3, 3.9] g/day and eGFR was 45.0 [26.8, 73.7] mL/min/1.73 m2. There was a significant reduction of proteinuria at 2, 4, 6 months when compared with baseline (2.3 [1.5, 4.1] vs. 1.5 [0.8, 2.3] g/day; 2.3 [1.1, 3.7] vs. 1.1 [0.6, 1.9] g/day; 2.1 [1.0, 2.7] vs. 0.9 [0.5, 1.7] g/day, all p values <0.01). The level of eGFR were comparable between at the baseline and 2, 4, 6 months of follow-up time (41.5 [29.7, 72.0] vs. 42.5 [28.8, 73.3] mL/min/1.73 m2; 41.0 [26.8, 67.7] vs. 44.7 [31.0, 67.8] mL/min/1.73 m2; 33.7 [24.0, 58.5] vs. 32.6 [27.8, 57.5] mL/min/1.73 m2, all p values >0.26). Telitacicept was well tolerated in the patients., Conclusions: This study indicates that telitacicept alone or on top of steroids therapy can significantly and safely reduce proteinuria in patients with IgAN. The long-term kidney protection still needs to be confirmed in large phase III trial., (© 2024 S. Karger AG, Basel.)

Introduction: Mycophenolate mofetil (MMF) is widely used off-label in patients with immunoglobulin A nephropathy (IgAN), although the literature does not consistently agree on its efficacy and safety., Methods: We systematically searched PubMed, Embase, CENTRAL, CNKI, VIP, Wanfang Data, and SinoMed from their inception to August 2023. We included randomized controlled trials that enrolled patients of IgAN who received MMF treatment and compared effects with placebo or as an add-on therapy to usual care. Literature screening, risk of bias assessment, and data extraction were independently conducted in duplicate. Fixed-effects or random-effects meta-analyses were performed for pooling data where eligible. The primary outcomes were the composite kidney outcomes of major adverse kidney events (MAKDE) defined as doubling of serum creatinine, end-stage renal disease (ESRD), or death from a kidney disease-related or cardiovascular cause., Results: Of 13 studies identified, 918 participants (463 [50.4%] treated with MMF) with IgAN were included in the analysis. MMF treatment in IgAN was associated with decreasing the occurrence of MAKDE (relative risk [RR], 0.32; 95% confidence interval [CI], 0.13-0.77), reducing proteinuria (RR, 1.41; 95% CI, 1.22-1.64), and lessening the probability of doubling blood creatinine (RR, 0.32, 95% CI, 0.14-0.72). No significant differences were detected in the incidence of ESRD (RR, 0.87, 95% CI, 0.38-2.03), or progression of chronic kidney disease (RR, 1.01; 95% CI, 0.22-4.57). Patients receiving MMF had a higher risk of infection (RR, 2.20; 95% CI, 1.21-4.00)., Conclusion: MMF administration in IgAN indicates promising in decreasing the occurrence of MAKDE, reducing proteinuria level, and lessening the probability of doubling blood creatinine, but also comes with the risk of infection. These findings tend to be introduced to non-Caucasian population. The long-term favorable effects that MMF improved kidney outcomes still need further cross-regional and cross-ethnical verification., (© 2024 S. Karger AG, Basel.)

We present a unique case of concurrent Fabry disease (FD) and IgA nephropathy (IgAN) in a 27-year-old female with a 10-year history of Crohn's disease (CD). The patient presented to the nephrology clinic with microscopic haematuria and proteinuria on routine tests. A kidney biopsy revealed mesangial matrix widening, mesangial cell proliferation, and podocyte enlargement with prominent lacy and clear cytoplasm, as observed with haematoxylin and eosin staining. Immunofluorescence staining demonstrated diffuse immunoglobulin A deposits in the mesangium. Electron microscopy identified myelin-like figures in the cytoplasm of podocytes and electron-dense deposits in the mesangium, confirming IgAN and suggesting FD. Subsequent testing showed low alpha-galactosidase A (α-gal) enzyme activity in the patient's white blood cells, confirming the FD diagnosis. Enzyme replacement therapy was initiated following the diagnosis. To our knowledge, this is the first reported case of the coexistence of FD, IgAN, and CD in a single patient. This case highlights the importance of considering FD in patients with proteinuria, emphasising the need for comprehensive diagnostic evaluations in complex cases., (© 2024 Asian Pacific Society of Nephrology.)

Background: The systemic inflammatory response index (SIRI), a straightforward and easily accessible measure of inflammation and prognosis, has drawn more attention lately. It is unknown, however, if SIRI is important for IgA nephropathy (IgAN) patients' outcomes. To better clarify these concerns, we conducted this investigation., Method: This retrospective study involved 981 patients with biopsy-confirmed IgAN from West China Hospital of Sichuan University between 2008 and 2019. The patients were divided into two groups based on the SIRI's optimal cut-off value calculated by the X-tile: the low SIRI group (SIRI ≤ 0.63, n = 312) and the high SIRI group (SIRI > 0.63, n = 669). Basic clinical characteristics at the time of renal biopsy were evaluated, and the relationship between SIRI and the combined endpoint was analyzed. We also used the Cox proportional hazard model and Kaplan‒Meier curve to evaluate the renal prognosis of IgAN., Results: A total of 981 IgAN patients were included. During a median follow-up period of 56.7 months (36.8-80.4 months), 122 patients progressed to the combined endpoint (12.4%). Patients were divided into a low SIRI group (SIRI ≤ 0.63, n = 312) and a high SIRI group (SIRI > 0.63, n = 669) according to the optimal cut-off value of the systemic inflammatory response index (SIRI). Further analysis showed that a higher SIRI value was significantly associated with the risk of IgAN patients reaching the composite endpoint (HR 1.62, 95% CI 1.02-2.56, p = 0.041)., Conclusion: High SIRI is a significant and independent risk factor for renal disease progression in IgAN patients., Competing Interests: Declarations. Conflict of Interest: The authors declare no potential conflicts of interest concerning the research, authorship, and/or publication of this article. Ethical Approval: This research was in compliance with the Declaration of Helsinki and approved by the Ethics Committee of West China Hospital of Sichuan University (ethical approval number 2019–33). Consent to Participate: Written informed consent was obtained from each patient., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Patients with glomerular disease are at high risk of cardiovascular disease but the contribution of immunosuppression to this risk is unclear. In this retrospective cohort study of 1912 patients (comprised of 759 with IgA nephropathy, 540 with focal segmental glomerulosclerosis, 387 with membranous nephropathy and 226 with minimal change disease) from British Columbia, Canada, we evaluated the association between exposure to specific immunosuppressive medications and a composite outcome including coronary artery, cerebrovascular and peripheral arterial events. Survival models were adjusted for baseline cardiovascular risk factors, type of glomerular disease, estimated glomerular filtration rate (eGFR) and proteinuria over time. During a median follow-up of 6.8 years, 212 patients (11.1%) experienced the primary outcome. Corticosteroid exposure was not significantly associated with the primary outcome after adjusting for cardiovascular risk factors. In fully adjusted models, cumulative calcineurin inhibitor exposure at modest (150-300 defined daily doses [DDD]) and higher (300 or more DDD) doses were associated with a 2-fold higher risk of cardiovascular events (hazard ratio 2.98, 95% confidence interval 1.27-6.95) and (2.78, 1.32-5.84), respectively. A peak daily dose of antimetabolite (azathioprine, mycophenolate mofetil and mycophenolate sodium) of 0.5 or more DDD was associated with higher risk of cardiovascular events after adjustment for baseline risk factors and type of glomerular disease, but not after adjusting for time-varying eGFR and proteinuria (1.70, 0.91-3.20). Each 10 grams of cumulative cyclophosphamide exposure was associated with a 1.5-fold higher risk of cardiovascular events in a fully adjusted model (1.46, 1.22-1.75) Thus, our findings suggest that immunosuppressive therapies used in the treatment of glomerular disease may have different cardiovascular risk profiles, which should be considered when deciding on immunosuppression for individual patients and as a safety endpoint in future clinical trials., (Copyright © 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Introduction: The role of dietary sodium intake in the risk of chronic kidney disease progression remains controversial. This study aimed to evaluate the association of urinary sodium excretion and progression of IgA nephropathy., Methods: We assessed 596 patients with IgA nephropathy, and urinary sodium excretion was measured at the time of kidney biopsy. Cox proportional hazards models and restricted cubic splines were used to assess the association between urinary sodium excretion and kidney disease progression events, defined as 50% eGFR decline or development of kidney failure., Results: After a mean follow-up of 58.9 months, a total of 75 (12.6%) participants of IgA nephropathy reached composite kidney disease progression events. The risk of kidney disease progression events was higher in patients with higher urinary sodium excretion. After adjustment for traditional risk factors, higher levels of ln-transformed urinary sodium excretion was associated with the kidney disease progression events in patients with IgA nephropathy (HR: 2.1; 95% CI: 1.4-3.2). In reference to the first tertile of urinary sodium excretion, hazard ratios were 1.9 (95% CI: 1.0-3.4) for the second tertile and 2.1 (95% CI: 1.1-3.9) for the third tertile., Conclusion: Higher levels of urinary sodium excretion were associated with kidney disease progression events in IgA nephropathy independent of clinical and biopsy characteristics., (© 2024 S. Karger AG, Basel.)

Background: Although glomerular diseases are the third most frequent cause of end-stage kidney disease worldwide, little is known about their long-term outcomes., Methods: In patients with chronic kidney disease (CKD) stage 3-5 enrolled in the Swedish Renal Registry, we compared risks of hospitalization, kidney replacement therapy (KRT), major cardiovascular events (MACE), and death of the four most frequent primary glomerular diseases (IgA nephropathy [IgAN], focal segmental glomerulosclerosis [FSGS], minimal change disease [MCD], and membranous nephropathy [MN]), and patients with CKD due to the most common non-communicable diseases (control-CKD)., Results: We identified 2396 patients with glomerular disease (97% biopsy-proven, 69% men, 57 years, eGFR 29 mL/min/1.73 m 2 , uACR 88 mg/mmol, 1524 with IgAN, 398 FSGS, 94 MCD, and 380 MN) and 37,697 controls (64% men, 74 years, eGFR 25 mL/min/1.73 m 2 , uACR 23 mg/mmol), mainly with diabetic nephropathy and nephroangiosclerosis. The median follow-up was 6.3 (3.3; 9.9) years. Compared with control-CKD, patients with primary glomerular diseases generally had a lower risk of hospitalization, MACE (adjusted hazard ratios [HRs] ranging from 0.44 to 0.88 depending on the etiology) and death (HRs ranging 0.45-0.76). Patients with IgAN and FSGS had a faster eGFR decline and a higher rate of KRT (HRs 1.26 [95%CI: 1.15-1.37] and 1.34 [1.15-1.57], respectively). Conversely, patients with MN and MCD had a lower KRT rate and slower eGFR decline., Conclusion: Despite having a lower relative risk of hospitalization, cardiovascular events and mortality, patients with IgAN and FSGS are at higher risk of CKD progression than the most common etiologies of CKD, emphasizing the need for more stringent treatment strategies in these patients., (© 2024 The Author(s). Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.)

A 3-year-old boy initially presented with purpura-like rashes and nephrotic syndrome, suspected to be IgA vasculitis nephritis (IgAVN). The suggestion of kidney biopsy was rejected. Although the patient responded well to glucocorticoids, they later developed recurrent proteinuria, refractory diarrhea, and subsequent metabolic acidosis. Kidney biopsy showed membranous nephropathy with positive semaphorin 3B expression, indicative of other kidney diseases rather than IgAVN. Although his kidney responded well to glucocorticoid combined with cyclosporine A treatment regimen, enteropathy and severe food allergy still progressed afterwards as evidenced by villous atrophy on gastrointestinal endoscopy examination. Whole exome sequencing identified a heterozygous missense variant in exon 11 of FOXP3: c.1121 T > G, confirming the diagnosis of immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome. The case expanded the phenotypic spectrum of IPEX syndrome, suggesting high phenotypic heterogeneity despite similar genotypes. It also put emphasis on the significance of kidney biopsy to differentiate IgA vasculitis nephropathy from other immune disorders., Competing Interests: Declarations. Consent to participate: The patient has consented for the use of their data in this publication. Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Introduction: IgA nephropathy (IgAN) is one of the most prevalent forms of glomerulonephritis worldwide, particularly affecting 40-50% of the East Asian population. Cardiovascular mortality represents a leading cause of death in patients with IgAN. Left ventricular hypertrophy (LVH) serves as a predictor of heart failure and cardiovascular mortality. Previous studies have indicated that Triglyceride glucose-body mass index (TyG-BMI), a surrogate marker for insulin resistance surrogates, correlated with the development of LVH. However, there is a lack of information available regarding the association between TyG-BMI and LVH in patients with IgAN. This study aims to explore the relationship between TyG-BMI and LVH in this population., Methods: This retrospective study was conducted in the Fifth Affiliated Hospital of Sun Yat-sen University recruiting inpatients with renal biopsy-confirmed IgAN who were over the age of 18 years. Left ventricular dimensions were assessed through echocardiography. Linear regression and multivariate logistic regression analyses were performed using R language software and SPSS to investigate the association between TyG-BMI levels and LVH risk. Statistical significance was set at p < 0.05., Results: A total of 327 patients with IgAN were enrolled in this study. Left ventricular mass index (LVMI) was positively correlated with TyG-BMI index (corr. coefficient: 0.453, p < 0.001) and inversely correlated with eGFR (corr. coefficient: -0.392, p < 0.001). After adjusting for age, gender, smoking, alcohol use, hemoglobin, low-density lipoprotein cholesterol, Scr, and urine output, advanced age and higher levels of hemoglobin and Scr were independently associated with increased TyG-BMI (p < 0.05). The odds ratios of the highest quartile of TyG-BMI compared with the lowest quartile were 8.39 (95%CI 1.66-42.39; p = 0.010)., Conclusions: Our findings indicated that the TyG-BMI level was positively correlated with LVMI. A high TyG-BMI level was independently associated with an increased risk of LVH in patients with IgAN. TyG-BMII demonstrated predictive ability for LVH in IgAN patients., Competing Interests: Declarations. Ethics approval and consent to participate: Our study was approved by the Ethics Committee of the Fifth Affiliated Hospital of Sun Yat-sen University which is followed the guidelines outlined in the Declaration of Helsinki. An exemption for informed consent was applied and approved by the Ethics Committee, because this retrospective study only involved the clinical data and completed test results without any intervention in the diagnosis and treatment of the patients. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Immunoglobulin A (IgA) nephritis (IgAN) and renal IgA vasculitis (IgAV) show renal IgA deposits, but whether these two diseases are distinct entities or a spectrum of the same condition is under debate. In this study, we add perspective by contrasting the clinical course and histological presentation using the Oxford classification and the National Institutes of Health lupus nephritis activity index (LN-AI) and chronicity index (LN-CI) in IgAN and IgAV., Methods: In this single-centre, retrospective study, kidney biopsies of 163 adult patients with IgAN and 60 adult patients with IgAV were compared according to the Oxford MEST-C score, LN-AI and LN-CI. At the time of biopsy, clinical presentation was compared in terms of age, arterial hypertension, diabetes mellitus, extrarenal manifestations, estimated glomerular filtration rate, proteinuria and urine sediment. IgAV patients and all IgAN patients with crescents received immunosuppressive treatment. After biopsy, kidney function was followed until patients reached end-stage renal disease (ESRD) or they died., Results: The clinical course and kidney histology differ in IgAN and IgAV. IgAV patients showed more microhaematuria and nephritic sediment, while IgAN patients had a greater history of arterial hypertension, more proteinuria and a higher risk for ESRD. These clinical differences were associated with histological differences, as kidney biopsies of IgAN patients were characterized by glomerulosclerosis and tubular atrophy while kidney biopsies of IgAV patients were characterized by endocapillary hypercellularity and crescents. Overall, tubular atrophy and an LN-CI ≥4 were associated with a higher risk for ESRD in IgAN and IgAV., Conclusion: Our study supports the notion that IgAN and IgAV follow distinct courses, suggesting that they require different treatment strategies. Moreover, we make a point that the Oxford classification and LN-CI can be useful in categorizing and predicting long-term prognosis not only in IgAN, but also in IgAV., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Background and Aim: Renal involvement in Crohn's Disease (CD) was rare in the population. Little was known between IgA nephropathy and CD. This study aimed to investigate the differences in clinical and outcome features of CD-associated IgA nephropathy (CD-IgAN) and primary IgA nephropathy (PIgAN)., Methods: Clinical data of patients diagnosed with IgAN by kidney biopsy were collected in the Sixth Affiliated Hospital of Sun Yat-sen University from January 1st, 2016 to June 1st, 2023. 17 patients with CD-IgAN and 87 patients with PIgAN were enrolled in this retrospective study., Results: Compared with PIgAN patients, CD-IgAN patients had lower levels of urinary protein excretion (1.57 g per 24 h vs. 0.33 g per 24 h, p < 0.01), but higher levels of estimated glomerular filtration rate (77.63 ± 40.11 ml per min per 1.73m 2 vs. 104.53 ± 32.97 ml per min per 1.73m 2 , p = 0.008). From the point of renal pathology of PIgAN, patients with CD-IgAN had a less incidence of tubular atrophy or interstitial fibrosis (p = 0.001). CD-IgAN patients had a higher incidence of complete remission of proteinuria (45.8% vs. 81.8%, p = 0.031) or hematuria (10.4% vs. 45.4%, p = 0.019) than PIgAN patients after twelve-month treatments., Conclusions: CD-IgAN manifests a milder progression of renal function than those PIgAN. After the treatment, proteinuria or hematuria are more prone to remit in patients with CD-IgAN., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

A 66-year-old non-smoker presented with a 2-week history of new-onset pedal oedema and gross haematuria. On evaluation, he was found to be hypertensive and oedematous with a haemoglobin of 19.1 g/dl, platelet count of 546,000/mm 3 , and creatinine of 2.6 mg/dl. Urine examination revealed abundant RBCs with 3+ albumin on three separate occasions. His 24-h urine protein level was 3830 mg/day, with a serum cholesterol level of 303 mg/dl. Secondary erythrocytosis and thrombocytosis tests were negative. Bone marrow examination revealed hypercellularity, erythroid hyperplasia, tight clusters of large megakaryocytes, and megakaryocytic hyperplasia suggestive of polycythemia vera. PCR analysis revealed a JAK2V617 F (exon 14) mutation. In view of nephrotic syndrome, azotemia, and microscopic haematuria, a renal biopsy was performed, which revealed features of IgA nephropathy with advanced interstitial fibrosis and tubular atrophy. He was started on angiotensin receptor blockers with hydroxy urea as a part of treatment. This case report highlights the association of glomerular disease with polycythaemia vera and the need of prompt renal biopsy for diagnosis and management., Competing Interests: Declarations. Conflict of interest: The authors declare that they have no competing interests. Ethical approval: This case report was drafted after written informed consent of the patient in conformity with CARE clinical case reporting guidelines and Declaration of Helsinki. The authors are accountable for all aspects of the work (including full data access, integrity of the data, and accuracy of the data analysis) to ensure that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved., (© 2024. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

IgA nephropathy (IgAN) is the most common type of primary glomerulonephritis worldwide and leads to end-stage kidney disease. The proteinuria selectivity index (PSI) has been used to assess the prognosis in nephrotic syndrome, but its predictive value in patients with IgAN remains unclear. This single-center retrospective cohort study included patients who diagnosed with IgAN between March 2012 and March 2020. The PSI was calculated at the time of kidney biopsy. Patients were followed up from the time of kidney biopsy to kidney replacement therapy, death, transfer to another facility, or study completion. Ninety-four patients with a median age of 51 years were enrolled and divided according to the cutoff value of PSI determined by the receiver operating characteristic curve analysis into low-PSI (PSI <0.243, n  = 39) and high-PSI groups (PSI ≥0.243, n  = 55). The median follow-up duration was 70 months. Rates of remission of proteinuria and survival without a two-fold increase in serum creatinine were significantly better in the low-PSI group (both p  < 0.01, log-rank test). Cox regression analysis showed that a low PSI was significantly associated with an increased likelihood of remission of proteinuria and hematuria (hazard ratio [HR] 1.96; 95% confidence interval [CI] 1.02-3.85 and HR 1.75; 95% CI 1.01-3.13, respectively), and a decreased risk of a two-fold increase in serum creatinine (HR 0.10; 95% CI 0.01-0.81). In conclusion, The PSI could have the potential to support the assessment of the prognosis of IgAN, in addition to established prognostic markers, by reflecting the overall glomerular permeability.

Anti-glomerular basement membrane (GBM) disease is a rare autoimmune condition characterized by the presence of positive anti-GBM autoantibodies, linear deposition of immunoglobulin G (IgG) along the GBM and severe kidney injury. In a limited number of cases, the association of anti-GBM disease with other glomerulonephritis has been reported. Herein, we present the case of a 66-year-old female patient with progressive worsen kidney function and decreased urine output. A renal biopsy revealed crescent glomerulonephritis with lineal IgG deposition along the GBM and mesangial IgA deposition, which supported the diagnosis of concurrent anti-GBM disease and IgA nephropathy (IgAN). In an extensive literature review, we identified a total of thirty-nine patients were reported anti-GBM disease combined with IgAN. The clinical characteristics of these patients demonstrate that the anti-GBM disease combined with IgAN tends to be milder with a more indolent course and a better prognosis than the classic anti-GBM disease, and its potential pathogenesis deserves to be further explored.

Background: Immune and inflammatory factors are considered the basic underlying mechanisms of IgA nephropathy (IgAN). The systemic immune inflammation index (SII) is a new inflammatory biomarker and has been identified as a prognostic indicator for various diseases. However, limited studies have been conducted on the prognostic value of the SII in patients with IgAN, and we aimed to address this gap., Methods: A total of 374 patients with IgAN confirmed by renal biopsy performed from 1 January 2015 to 1 April 2019, were retrospectively included. The follow-up period of all patients was at least 12 months after diagnosis, and the endpoint was defined as end-stage kidney disease (ESKD). Patients were further divided into a high-risk group (SII ≥ 456.21) and a low-risk group (SII < 456.21) based on the optimal cutoff value of the SII determined by receiver operating characteristic (ROC) curve analysis. Baseline clinicopathological parameters were compared between the groups, and Cox proportional hazards analyses and Kaplan-Meier analysis were performed to assess renal survival in IgAN patients., Results: After a median follow-up period of 32.5 months, a total of 53 patients eventually reached ESKD. Patients in the high-SII group tended to have a lower hemoglobin level ( p  = 0.032) and eGFR ( p  < 0.001), a higher serum creatinine level ( p  = 0.023) and 24-hour total protein level ( p  = 0.004), more severe tubular atrophy and interstitial fibrosis ( p  = 0.002) and more crescents ( p  = 0.030) than did those in the low-SII group. Univariate and multivariate Cox regression analyses demonstrated that an SII ≥456.21 was an independent risk factor for poor renal survival in IgAN patients (HR 3.028; 95% CI 1.486-6.170; p  = 0.002). Kaplan-Meier analysis revealed that a high SII was significantly associated with poor renal prognosis ( p  < 0.001) and consistently exhibited remarkable discriminatory ability across different subgroups in terms of renal survival., Conclusion: A high SII was associated with more severe baseline clinical and pathological features, and an SII ≥456.21 was an independent risk factor for progression to ESKD in IgAN patients.

Background: During the run-in phase of the TESTING study, approximately half of patients with IgA nephropathy (IgAN) were excluded due to proteinuria below 1 g/24 h after intensive supportive therapy. The long-term prognosis of these patients needs further investigation., Methods: 112 screening failed patients in the TESTING study from 10 centers in China were enrolled in this retrospective study. The prognosis of 88 patients, who were excluded because of proteinuria below 1 g/24 h, was analyzed by Landmark Kaplan-Meier analysis. The composite kidney endpoint was defined by a  ≥ 50% reduction in eGFR, ESKD (eGFR <15 mL/min per 1.73 m 2 ), chronic dialysis for at least 6 months, or renal transplantation., Results: In total, 88 patients were excluded due to proteinuria less than 1 g/24 h. During the follow-up, 73/88 (83.0%) patients received renin-angiotensin system blocker. 72/88 (81.8%) had stable proteinuria remission and did not receive immunosuppressive therapy (IST), and 16/88 (18.2%) received IST because of a relapse of proteinuria. Landmark Kaplan-Meier analysis revealed that, the kidney survival from dialysis or composite kidney outcome of these excluded patients with IST was similar to those without IST during the early stages of follow-up (dialysis, before 60 months, p  = 0.778; composite kidney outcome, before 48 months, p  = 0.862); whereas the risk for dialysis of patients receiving IST was significantly higher than those without IST after 60 months (OR = 11.3, p  = 0.03). Similarly, the risk for the composite kidney outcome of patients receiving IST was also significantly higher than those without IST after 48 months (OR = 5.92, p  = 0.029)., Conclusions: IgAN patients who maintained a persistent remission of proteinuria after intensive supportive therapy had a much better long-term kidney outcome than those who experienced a relapse of proteinuria and needed IST.

We herein report a case of IgA nephropathy in a 20-year-old male who maintained a complete remission of minimal change nephrotic syndrome (MCNS) through the administration of rituximab (RTX). He was diagnosed with nephrotic syndrome at 4 years of age. After he relapsed frequently, he was diagnosed with MCNS at 8 years of age based on the findings of a kidney biopsy. At 13 years of age, RTX therapy was initiated to maintain a complete remission after steroid treatment. MCNS recurred twice, including the time in which the interval between the RTX administrations was long. Whenever he relapsed, remission induction was achieved using steroids, and remission maintenance was achieved using RTX. Five months after the 7th RTX administration, the serum IgA level started to increase. After the 9th RTX administration, he demonstrated microhematuria despite the urinary protein level indicating complete remission. At the 10th administration, the urinary protein and the red-blood cell casts were also observed. A renal biopsy was performed 84 months after the initial administration of RTX, and the patient was diagnosed with complications of IgA nephropathy. RTX is not considered to be a useful treatment for IgA nephropathy. The reasons for this are due to the fact that IgA1 does not decrease even following the administration of RTX, because B cells residing in the mucosa may not be deleted by RTX, and IgA production may also continue due to the presence of CD20 - long-lived plasma cells. Even when administering RTX, if there are findings of glomerulonephritis on urine testing, the possibility of IgA nephropathy must be considered., Competing Interests: Declarations. Conflict of interest: All the authors have declared no competing interest. Informed consent: Informed consent was obtained from the patient in the present study. Human and animal rights: This article does not contain any studies with human participants or animals performed by any of the authors., (© 2024. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

Background: Hepatitis B virus (HBV) is a risk factor for the progression of immunoglobulin A (IgA) nephropathy. The effect of HBV antigens deposition in kidneys and treatment influencing HBV deposition requires further investigation., Methods: We analyzed 198 patients with IgAN, including 99 patients with HBV infection and 99 propensity score-matched patients without HBV infection. The primary outcome was a composite of 30% decrease in eGFR from the baseline, kidney failure and all-cause mortality. A Cox proportional hazard model was used to assess the impact of both HBV positive in the serum and HBV antigens deposition in the kidneys on renal outcomes., Results: Among 198 individuals, 27 primary composite outcome events were observed, of which 20 (20%) in the HBV positive group and seven (7%) were in the HBV-negative group. The former had a 2.72-fold increased risk of primary outcome events (adjusted hazard ratio: 2.22; 95% confidence interval: 0.89-5.53). HBV antigens deposition in kidneys increased the risk significantly after adjusting for confounders at the latest follow-up (adjusted hazard ratio: 7.49; 95% confidence interval: 1.00-56.04). Antiviral treatment did not influence the deposition of HBV antigens., Conclusions: HBV antigen deposition in the kidneys, compared with no deposition in the kidneys, was associated with a 7.49-fold increased risk of renal prognosis in patients with IgA nephropathy.

Background: Immunoglobulin A nephropathy (IgAN) is a complex renal disease with a highly variable clinical course. Identifying reliable prognostic markers is crucial for risk stratification and treatment decisions. This study aimed to understand the influence of different proportions of crescents (Cs) on the progression of IgAN., Methods: Four databases (PubMed, Web of Science, Embase, and Cochrane Library) were searched until September 25, 2023. The study encompassed IgAN patients, focusing on kidney outcomes and end-stage kidney disease (ESKD). Statistical analysis included calculating hazard ratios (HR) for binary outcomes and examining publication bias., Results: The meta-analysis involved thirteen studies comprising 11,849 patients. For kidney outcomes, crescent formation may be linked to an elevated risk (HR = 2.01, 95%CI 1.40-2.87, P < 0.001). Furthermore, significantly increased risks of kidney outcomes were observed with a crescent proportion > 10 (HR = 1.8, 95%CI 1.32-2.45, P < 0.001) and > 25%(HR = 2.11, 95% CI 1.47-3.02, P < 0.001). Regarding ESKD, a proportion > 25% also displayed an elevated risk (HR = 1.70, 95% CI 1.18-2.44, P = 0.004). However, a proportion > 10% (including > 25%) did not show a significant association with ESKD (HR = 1.12, 95% CI 0.36-3.47, P = 0.842) versus less., Conclusions: This systematic review and meta-analysis established a strong association between crescent proportions and the progression of IgAN. Higher proportions, notably exceeding 25%, were reliable prognostic markers, indicating a greater risk of adverse kidney outcomes and ESKD. These findings have significant clinical implications, offering the potential for more precise risk stratification in IgAN patients., (© 2024. The Author(s).)

Background: To investigate the clinical features, kidney pathology, treatment regimens, and clinical outcomes of IgA vasculitis nephritis (IgAVN) with nephrotic-range proteinuria in children., Methods: A retrospective review of children diagnosed with IgAVN between January 2019 and December 2022 was conducted. Participants were divided into two groups based on their urine protein/creatinine (UPCR) levels. Biodata, clinical characteristics, laboratory findings, pathologic features, treatment regimens, and outcomes were abstracted from case records and analyzed., Results: A total of 255 children were identified, 94 with nephrotic-range proteinuria (UPCR ≥ 200 mg/mmol) and 161 with non-nephrotic proteinuria (UPCR < 200 mg/mmol). Patients in the nephrotic-range proteinuria group were significantly younger and had worse grades of glomerular and acute tubulointerstitial injury compared to those in the non-nephrotic proteinuria group. Higher levels of blood urea nitrogen (BUN), D-dimer (DD), and fibrin degradation products (FDP), and lower levels of total protein (TP), albumin (ALB), urine creatinine (Cr), prothrombin time (PT), activated partial thromboplastin time (APTT), IgG, CD3 + cells, and CD4 + cells were found in patients in the nephrotic-range proteinuria group. Clinical outcome of patients with nephrotic-range proteinuria was significantly associated with ISKDC grading, proportion of glomerular crescents and severity of acute tubulointerstitial injury., Conclusions: Children with nephrotic-range proteinuria exhibit more severe disordered immunologic function, hypercoagulability, glomerular and tubulointerstitial pathological damage, and have worse outcomes than those with lower proteinuria levels. Clinicians should pay great attention to the kidney injury and more extensive studies are required to identify optimal treatment regimens to improve outcomes in patients., (© 2024. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Rationale & Objective: Little is known regarding the association between chronic tonsillitis and the onset of IgA nephropathy (IgAN). In the present study, we examined the potential relationship between chronic tonsillitis and a subsequent risk of developing IgAN., Study Design: Observational cohort study., Setting & Participants: 4,311,393 individuals without a history of IgAN identified between January 2005 and May 2022 within a Japanese nationwide epidemiological database, the JMDC Claims Database, representing health claims to over 60 insurers., Exposure: Comorbid chronic tonsillitis based on diagnosis codes., Outcome: IgAN occurrence., Analytical Approach: Cause-specific Cox proportional hazards analysis adjusting for potential confounding factors was employed to estimate hazard ratios (HRs)., Results: Comorbid chronic tonsillitis was identified in 12,842 individuals, constituting 0.3% of the cohort. The cohort had a median age of 44 years (IQR, 36-53), and males accounted for 57.9%, with a follow-up of 1,089 days (IQR, 532-1,797), during which 2,653 cases of IgAN developed. Cumulative incidence curve showed a higher cumulative incidence of IgAN in individuals with chronic tonsillitis compared with their counterparts without this condition. Multivariable cause-specific analysis further demonstrated that individuals with chronic tonsillitis had an elevated risk of developing IgAN, with HR of 2.72 (95% CI, 1.79-4.14)., Limitations: Potential residual confounders, and lack of consideration for ethnic distinctions., Conclusions: Using a large-scale epidemiological dataset, these findings suggest a relationship between chronic tonsillitis and an elevated risk of IgAN development in the general Japanese population., Plain-Language Summary: IgA nephropathy (IgAN), the most prevalent form of primary glomerulonephritis worldwide, is associated with unfavorable long-term kidney survival and life expectancy. Despite the substantial implications, the early detection of IgAN still remains challenging due to its commonly asymptomatic clinical presentation. Consequently, the exploration of risk factors assumes a critical research priority. Prior studies have reported the potential role of tonsilitis in the pathogenesis of IgAN. In this study, we assessed whether chronic tonsillitis was associated with the subsequent development of IgAN using a nationwide epidemiological dataset incorporating over 4,000,000 individuals. Within this large-scale cohort, our findings revealed an association between a history of tonsillitis and a greater risk of developing IgAN. These findings should heighten awareness of the potential susceptibility of people with chronic tonsilitis to IgAN., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Aim: IgA nephropathy (IgAN) is the most common primary glomerular disease worldwide. Pregnant IgAN patients are more susceptible to adverse pregnancy outcomes (APO). However, the risk factor for APO and its effects on the long-term renal outcome of pregnant IgAN patients remained unclear., Methods: We performed a retrospective observational study covering 2003-2019 that included 44 female IgAN patients with pregnancy history to investigate the risk factor for APO and its impact on clinical outcome in IgAN. Renal function outcome and proteinuria remission were evaluated in pregnant IgAN women with and without APO., Results: In this retrospective and observational study, we found that patients with APO exhibited higher levels of serum creatinine and IgM, and lower haemoglobin levels while other clinical characteristics, pathological characteristics and therapy protocol had no significant difference. We found that anaemia and a higher level of serum IgM were independent risk factors for APO. IgAN pregnant women without APO experienced a higher proportion of proteinuria remission than those with APO, but there is no difference in the renal function outcome., Conclusion: Pregnant IgAN patients with higher risks, including lower haemoglobin levels and higher IgM levels deserve intensive monitoring, and aggressive therapy to reduce proteinuria should be carried out in pregnant IgAN patients with APO., (© 2024 Asian Pacific Society of Nephrology.)

Background: Few studies have observed the direct effect of obesity on renal prognoses in immunoglobulin A nephropathy (IgAN) or separately evaluated its effects according to sex. We aimed to evaluate the direct and indirect effects of obesity on the renal outcomes of IgAN and observe these effects separately according to renal function and sex., Methods: We extracted patients with body mass index (BMI) descriptions from a multicenter retrospective cohort analysis in Japan, and excluded those with < 30 days of follow-up, diabetes mellitus, and steroid treatment. Patients were divided into normal (n = 720; 18.5 ≤ BMI < 25) and obese (n = 212; BMI ≥ 25) groups, which were then compared. The endpoints were a 1.5-fold increase in serum creatinine levels and the initiation of renal replacement therapy., Results: The obese group was older, included more males, and was more likely have hypertension, dyslipidemia, proteinuria, tubular atrophy, and lower renal function than the normal group. Patients with an eGFR < 60 mL/min/1.73 m 2 had well-matched characteristics between the groups; however, hypertension, low high-density lipoprotein cholesterol, and hypertriglyceridemia were more common in the obese group. Obesity contributed to tubular atrophy, even when adjusted for renal function. In addition, it contributed to proteinuria only in females. However, obesity itself was not a significant prognostic factor., Conclusions: Although no independent effect on renal prognosis was observed during the study period, the obese group had more risk factors for IgAN progression and obesity contributed to tubular atrophy and female proteinuria. Our results suggest that separately analyzing the prognostic effect of obesity according to sex is important., Competing Interests: Declarations Conflict of interest All authors have declared no competing interests regarding this study. Ethical approval All procedures were performed in accordance with the ethical standards of the responsible committee on human experimentation (Kitano Hospital Institutional Ethics Committee, approval number: 2106007) and the Helsinki Declaration of 1964 and later versions. Informed consent The data for this survey obtained from the patients’ medical records were anonymized for personal information so that the patients could not be identified. Anonymized data sets from each participating facility were used. Therefore, the requirement for written informed consent was waived., (© 2024. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

Background: Although vaccination has been reported to reduce the morbidity and severity of COVID-19 infection in patients with kidney disease, gross hematuria is frequently reported following vaccination in patients with IgA nephropathy. We investigated the frequency of gross hematuria following COVID-19 vaccination and its effect on renal function in IgA nephropathy patients., Methods: Adverse reactions after two or more COVID-19 vaccine doses were investigated in 295 IgA nephropathy patients attending Osaka Cty general hospital from September 2021 to November 2022. We compared differences in background characteristics and other adverse reactions between groups with and without gross hematuria after vaccination, and examined changes in renal function and proteinuria., Results: Twenty-eight patients (9.5%) had gross hematuria. The median age of patients with and without gross hematuria was 44 (29-48) and 49 (42-61) years, respectively, indicating a significant difference. The percentage of patients with microscopic hematuria before vaccination differed significantly between those with (65.2%) and without (32%) gross hematuria. Adverse reactions, such as fever, chills, headache and arthralgia, were more frequent in patients with gross hematuria. There was no difference in renal functional decline after approximately 1 year between patients with and without gross hematuria. We also found no significant changes in estimated glomerular filtration rate or proteinuria before and after vaccination in the gross hematuria group. However, some patients clearly had worsening of renal function., Conclusions: While COVID-19 vaccination is beneficial, care is required since it might adversely affect renal function in some patients., Competing Interests: Declarations Conflict of interest The authors declare that no conflicts of interest exist. Research involving human participants This study was approved by the ethics committee of Osaka City General Hospital (1709053) and was performed in accordance with the 1964 Declaration of Helsinki and its later amendments. Informed consent Informed consent was obtained from all individual participants included in the study., (© 2024. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

Aims/Background Both membranous nephropathy (MN) and immunoglobulin A nephropathy (IgAN) are immune complex-mediated glomerular diseases, but the concurrent occurrence of these two conditions in the same patient is not common, a phenomenon that is currently not supported by clinical data in terms of treatment and prognosis. This study explores the clinical and pathological characteristics, as well as the treatment outcomes, of patients affected by MN and IgAN simultaneously. Methods The clinical data, pathological features, and diagnostic and therapeutic information of seven cases of MN complicated by IgAN, treated between December 2015 and December 2022, were retrospectively analyzed. Results Among the seven cases, there were two male and five female patients, with an average age of 57.3 ± 9.2 years. All patients presented with clinical manifestations of proteinuria and edema upon admission, with an average 24-hour urine protein of 3716.6 ± 1519.4 mg/24 h. Phospholipase A2 receptor (PLA2R) expression was detected in all seven cases, and nephrotic syndrome was clinically diagnosed in five cases. Additionally, all seven cases showed microscopic hematuria, with intermittent gross hematuria in two cases. All seven patients included in this study underwent renal biopsy. After disease staging, the patients had MN stages I-III and IgAN stages II-III. Pathological findings revealed abnormal glomerular basement membrane (GBM) and diffuse immunoglobulin G (IgG) deposition in the subepithelial space, predominantly of the IgG4 subtype. Simultaneously, there was diffuse mesangial zone deposition of immunoglobulin A (IgA) to varying degrees, co-localization of complement component C3 and IgA, and mesangial cell proliferation. Treatment strategies included angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) in combination with steroids or immunosuppressive therapies such as tacrolimus, cyclophosphamide, and rituximab. After 2-6 months of treatment, all patients achieved complete remission with a favourable prognosis. Conclusion MN accompanied by IgAN tends to occur more frequently in middle-aged and elderly individuals, with a relatively low incidence. The latent feature of the comorbidities manifests as a form of IgAN superimposed on the background of MN. Utilizing ACEI or ARB in combination with steroids or various immunosuppressive therapies represents a potentially effective treatment strategy.

Introduction: The role of complement system in late stage of IgA nephropathy (IgAN) remains unknown. We therefore investigated the effects of complement system on worsening kidney function in advanced (stage 4 CKD) IgAN., Methods: Renal specimens of 69 IgAN patients who underwent renal biopsy during stage 4 CKD between 2010 and 2021, were stained using immunofluorescence (IF) and immunohistochemistry (IHC) for glomerular complement components. The primary outcome was progression to end-stage renal disease (ESRD). Associations of complement components with baseline clinicopathological characteristics and outcomes were assessed using multivariable Cox regression and Spearman analyses., Results: During a median follow-up of 18.0 months, 26 (37.7%) patients progressed to ESRD and none died. C1q and C3 deposition were detected in 12 and 66 patients, respectively. Higher eGFR [hazards ratio (HR), 0.852, 95% confidence interval (CI), 0.756-0.959; P = 0.008], higher C3 intensity (HR, 2.955, 95%CI, 1.063-8.220; P = 0.038) and T1-2 score (HR, 2.576, 95%CI, 1.205-5.576, P = 0.015) were predictive of time to ESRD in CKD 4 stage IgAN. Significant expressions of C1q (P = 0.005), C4d (P < 0.001), factor B (P < 0.001), C3 (P = 0.042) and C5b-9 (P = 0.004) were identified in ESRD group than in non-ESRD group by IHC, while MBL expression was low. Although they were not associated with baseline 24 h-UP, higher factor B and C1q expressions were both correlated with a lower baseline eGFR (P < 0.001 and = 0.04, respectively) and the deterioration of kidney function during follow-up (P = 0.046 and 0.015, respectively)., Conclusion: Complement deposition in IgAN patients with stage 4 CKD portends a faster deterioration of kidney function. Activation of classical and alternative complement pathways plays a major role in this stage., (© 2024. The Author(s).)

We experienced three cases of a fever and subsequent severe, prolonged gross hematuria after COVID-19 vaccination. A kidney biopsy revealed immunoglobulin A (IgA) nephropathy, and electron microscopy showed two types of podocytopathy (podocyte damage): loss of foot processes from the glomerular basement membrane and foot process effacement. Mesangial interposition was also present in cases 1 and 3 but not in case 2. Podocytopathy is known to be a cause of proteinuria; however, the reactions to COVID-19 vaccination described here suggest that it may also be related to hematuria in IgA nephropathy.

Objective: To explore the genetic etiology and clinical outcome of a child with co-morbid progressive IgA nephropathy and COQ8B-associated glomerulopathy., Methods: A child who was admitted to Peking University First Hospital on March 2, 2021 was selected as the study subject. Genomic DNA was extracted from peripheral blood samples from the child and his parents and sister. Whole exome sequencing was carried out, and candidate variant was verified by Sanger sequencing. This study was approved by the Peking University First Hospital (Ethics No. 2016[1029])., Results: The child, a 7-year-old boy who had developed proteinuria 8 months before, was diagnosed with IgA nephropathy (M1E1S1T1C1). With steroid, cyclophosphamide, cyclosporine and angiotensin-converting enzyme inhibitor therapy, partial remission of proteinuria was achieved. However, his serum creatinine level had increased from 53.8 mol/L at the onset of disease to 86.7 mol/L after 3.9 years, along with massive proteinuria. Kidney biopsy still indicated IgA nephropathy (M0E0S1T0C0). The child was found to harbor a homozygous c.737G>A (p.Ser246Asn) missense variant of the COQ8B gene, for which his parents and sister were heterozygous carriers. The variant was predicted to be pathogenic (PS1+PM2&#95;Supporting+PM3+PP3+PP4) based on the guidelines from the American College of Medical Genetics and Genomics. The child was treated with high-dose coenzyme Q10 in combination with steroid and/or mycophenolate mofetil, though his serum creatinine level still increased to 286 mol/L after 7.3 years, which conformed to a chronic kidney disorder with glomerular filtration rate category of G3b., Conclusion: The homozygous c.737G>A missense variants of the COQ8B gene probably underlay the progressive kidney dysfunction in this child. For children with IgA nephropathy presenting with atypical clinical manifestations, unsatisfactory therapeutic effect, and/or early onset of kidney function decline, coexistence of other diseases should be suspected.

We describe a case of full-house nephropathy without any underlying disease, including systemic lupus erythematosus. A 40-year-old woman was referred to our hospital with mild proteinuria and microscopic hematuria. The patient was diagnosed with immune complex-mediated glomerulonephritis with a predominant mesangioproliferative pattern based on renal histopathological results using full-house immunofluorescence staining. She showed no clinical criteria for the diagnosis of systemic lupus erythematosus, except for kidney disorders, and tested negative for antinuclear antibodies throughout her clinical course. However, in the second kidney biopsy, no C1q or C4 were detected in the immunofluorescence study, suggesting an immunoglobulin A nephropathy-like pattern. The patient responded favorably to corticosteroid treatment. We found a heterozygous CFHR3-CFHR1 deletion. The association between full-house nephropathy and CFHR3-CFHR1 deletion is unknown, but its influence on the histological pattern in our case is suspected. This indicates the diversity in the pathogenesis of non-lupus full-house nephropathy and warrants further investigation., (© 2024. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

Background: Sparsentan has shown positive effects on managing different subtypes of glomerulonephritis. The recent results of trials require a pooled analysis to validate these results., Aim: We aim to assess the safety and efficacy of sparsentan versus irbesartan for patients with IgA nephropathy and focal glomerulosclerosis (FSGS)., Methods: We conducted a systematic review and meta-analysis of randomized controlled trials retrieved by systematically searching PubMed, Web of Science, Scopus, and Cochrane through March 2024. We used Review Manager v.5.4 to pool dichotomous data using risk ratio (RR) and continuous data using mean difference (MD) with a 95% confidence interval (CI)., Results: Three studies with a total of 884 patients were included. Sparsentan was superior to irbesartan in improving urine protein to creatinine ratio (UP/C) (ratio of percentage reduction 0.66, 95% CI [0.58 to 0.74], P < 0.001); as well as the proportion of patients achieved complete and partial remission of proteinuria (RR = 2.57, 95% CI [1.73 to 3.81], P < 0.001) and (RR = 1.63, 95% CI [1.4 to 1.91], P < 0.001) respectively. Regarding the effect on the glomerular filtration rate, the results estimate did not favor either sparsentan or irbesartan (MD = 1.98 ml/min per 1.73mm2, 95% CI [-1.05 to 5.01], P = 0.2). There were no significant differences in adverse events except for hypotension, which showed higher rates in the sparsentan group (RR = 2.02, 95% CI [1.3 to 3.16], P = 0.002)., Conclusion: Sparsentan is effective and has a good safety profile for treating FSGS and patients with IgA nephropathy. However, more well-designed RCTs against ARBs, ACE inhibitors, and steroids with larger sample sizes are needed to get conclusive evidence., (© 2024. The Author(s).)

Background: Immunoglobulin A (IgA) vasculitis nephritis (IgAVN) is the most common secondary IgA nephropathy (IgAN). Urinary C4d have been identified associated with the development and progression in primary IgAN; however, its role in kidney disease progression of IgAVN is still unclear., Methods: This study enrolled 139 patients with IgAVN, 18 healthy subjects, 23 focal segmental glomerulosclerosis patients and 38 IgAN patients. Urinary C4d levels at kidney biopsy were measured using enzyme-linked immunosorbent assay. The association between urinary C4d/creatinine and kidney disease progression event, defined as 40% estimated glomerular filtration rate decline or end-stage kidney disease, was assessed using Cox proportional hazards models and restricted cubic splines., Results: The levels of urinary C4d/creatinine (Cr) in IgAVN and IgAN patients were higher than in healthy controls. Higher levels of urinary C4d/Cr were associated with higher proteinuria and severe Oxford C lesions, and glomerular C4d deposition. After a median follow-up of 52.79 months, 18 (12.95%) participants reached composite kidney disease progression event. The risk of kidney disease progression event was higher with higher levels of Ln(urinary C4d/Cr). After adjustment for clinical data, higher levels of urinary C4d/Cr were associated with kidney disease progression in IgAVN [per Ln-transformed urinary C4d/Cr, hazard ratio 1.573, 95% confidence interval (CI) 1.101-2.245; P = .013]. Compared with the lower C4d/Cr group, the hazard ratio was 5.539 (95% CI 1.135-27.035; P = .034) for the higher levels group., Conclusions: Higher levels of urinary C4d/Cr were associated with kidney disease progression event in patients with IgAVN., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Background: Behcet's disease (BD) is an inflammatory disorder of unknown cause that is characterized by recurrent oral aphthous ulcers, genital ulcers, uveitis, and skin lesions. Local vasculitis can cause damage to the visceral system, but it is rare in kidney patients, especially those with IgA nephropathy (IgAN). In China, a small number of related cases have been reported. Here we present a case of co-occurrence of BD and IgAN., Case Presentation: An 18-year-old female who presented with a history of recurrent oral ulcers was found ten years ago. Four years later, the patient presented with reddish nodules on the skin of both lower limbs and then presented with vulvar ulcers. This patient was clinically diagnosed with Behcet's disease after left calf skin biopsy and presented severe proteinuria and hematuria during this period. IgAN was diagnosed after percutaneous renal biopsy. The patient was treated with hormonal, anti-inflammatory, immunomodulatory, kidney protective, and protein-lowering urine agents. After 3 years of follow-up, the patient reappears oral ulcers, reddish nodules on the skin of both lower limbs and renal dysfunction., Conclusions: BD is less common in China and is clinically prone to missed diagnosis and misdiagnosis. BD with IgAN is rarer. We should regularly pay attention to the routine urine and renal function of BD patients for early detection and treatment and to prevent further progression of the disease., (© 2024. The Author(s).)

Aim: The aim of this study was to examine the clinical and pathological characteristics as well as the prognosis of immunoglobulin A nephropathy (IgAN) accompanied by renal thrombotic microangiopathy (rTMA) in paediatric patients., Methods: After balancing epidemiological characteristics and pathological types between groups, 427 patients (rTMA group: 23, non-rTMA group: 46) were included. The clinical and pathological features, prognosis and clinical risk factors of the two groups were analysed., Results: IgAN-rTMA children showed more severe clinical and pathological manifestations. The findings from the logistic regression analysis indicated that hypercellularity 1 (E1) (HR: 0.805, 95% CI: 0.763 ~ 1.452, P = .016), endocapillary proliferation (HR: 1.214, 95% CI: 0.093 ~ 4.815, P = .025) and C3 staining (HR: 7.554, 95% CI: 2.563 ~ 15.729, P = .037) were the risk factors for rTMA in children with IgAN. The renal survival in rTMA group was lower than non-rTMA group (χ 2  = 18.467, P = .000). Cox regression analysis showed that E1 (HR: 7.441, 95% CI: 1.095 ~ 10.768, P = .037), C3 disposition (HR: 3.414, 95% CI: 0.834 ~ 11.578, P = .027) and rTMA (HR: 8.918, 95% CI: 1.032 ~ 16.754, P = .041) were identified as independent risk factors for the development of end-stage renal disease (ESRD)., Conclusion: The presence of rTMA had a significant impact on the severity and prognosis of IgAN. And rTMA has been identified as an independent risk factor for the development of renal failure in children diagnosed with IgAN., (© 2024 Asian Pacific Society of Nephrology.)

When Berger et al. first reported IgA nephropathy in 1968, the prognosis was generally thought to be benign. However, as more case data were accumulated, it became evident that not all patients with IgA nephropathy necessarily had a good prognosis. IgA nephropathy has a significant morbidity, culminating in end-stage kidney disease (ESKD) in about 40% of patients without treatment within 20 years of the diagnosis. Although almost 20% of patients remain stable in their renal function, 30%-40% of patients develop ESKD from its onset. The important factors of renal outcome in patients with IgA nephropathy is the severity of histopathological findings, heavy proteinuria, long duration of proteinuria, haematuria and hypertension., (© 2024 Asian Pacific Society of Nephrology.)

Purpose: Diabetes mellitus (DM) is the leading cause of chronic kidney disease (CKD) in the population. In patients with diabetes mellitus, the incidence of non-diabetic nephropathy (NDNP) has been estimated to range from 3% to 69.5%. Personal judgment is frequently employed while deciding whether or not to do a kidney biopsy (KB) on diabetic patients. NDNP alters the prognosis and course of treatment for people with DM. In our study, we examined the incidence of NDNP concurrent with the progression of diabetes mellitus, as well as the laboratory and clinical indicators that could be utilized to forecast it., Methods: A retrospective analysis of 76 diabetic patients who underwent KB was conducted. Based on the pathological diagnoses of these patients, they were categorized as DNP (diabetic nephropathy) or NDNP. The definition of HbA1c variability was determined by calculating the mean HbA1c and the average value of the HbA1c measurements, as well as the standard deviation (SD) for each participant., Results: NDNP was detected in 50% of 76 patients. Among patients with NDNP, 36.8% had focal segmental glomerulosclerosis (FSGS), 23.6% had membranous glomerulonephritis, and 7.8% had IgA nephritis. The NDNP group exhibited significantly higher rates of female gender, absence of diabetic retinopathy, shorter time to diagnosis of diabetes mellitus, chronic kidney disease, and proteinuria, less intensive medication for diabetes mellitus, presence of hematuria and leukociduria, immunological serological marker positivity, and non-HbA1C variability. Risk factors for predicting non-diabetic nephropathy, as determined by multivariate analysis, included female gender, the absence of diabetic retinopathy, non-HbA1c variability and a positive immunological serological test., Conclusion: In this study, a significant number of diabetic patients with chronic kidney disease were diagnosed with NDNP. Identifying these patients allows for treatment of the specific underlying disease. Factors such as the absence of DR, non-HbA1c variability, female gender, and immunological serological test positivity can predict NDNP and guide the clinician's decision on kidney biopsy. Further prospective studies are warranted to validate the efficacy of potential predictive factors like HbA1c variability., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Purpose: To evaluate the differences in clinicopathological features and outcomes of IgA nephropathy (IgAN) patients with and without nephrotic syndrome., Methods: In this retrospective cohort study, IgAN patients from January 2006 to December 2011 in the First Affiliated Hospital of Sun Yat-sen University were enrolled and followed up to Dec 31, 2013. Logistic and Cox regression were conducted to evaluate the associated factors of nephrotic syndrome (NS) and its relation with outcomes of creatinine doubling and progression to end-stage kidney disease (ESKD)., Results: A total of 1413 patients with IgAN were enrolled in this study, 57 (4.0%) of whom exhibited NS. Meanwhile, 13 (22.8%) of NS IgAN patients had minimal change disease (MCD). Logistic regression showed that more presence of hypertension, less glomerular sclerosis, less tubular atrophy/interstitial fibrosis, and lower density of IgA deposition in mesangial region were significantly associated with NS IgAN that were independent of age and gender. In addition, a total of 921 patients (890 with non-NS IgAN and 31 with NS IgAN) were followed up to Dec 31, 2013. After adjusting for age, sex, baseline estimated glomerular rate, hypertension and hemoglobin, no significant difference was observed in outcomes of serum creatinine doubling and ESKD between patients with or without NS IgAN., Conclusions: Prevalence of NS IgAN patients was 4.0%, and 22.8% of them had MCD. Patients with NS IgAN had more severe clinical but less severe pathological features. However, outcomes of serum creatinine doubling and ESKD were not significantly different between patients with or without NS IgAN., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: In August 2023, our hospital confirmed a case of IgA nephropathy complicated with pulmonary infection by Mycobacterium abscess. The patient sought medical attention at our hospital due to "gross hematuria for 10 years, recurrence for 10 days, coughing and sputum production". The patient had pulmonary tuberculosis 15 years ago and had been cured. He had bronchiectasis for 10 years., Methods: Chest CT, fiberoptic bronchoscopy examination, urine routine (urine analysis + sediment quantification), urine trace protein measurement//urine creatinine (random urine), urine protein quantification (24-hour urine), antinuclear antibody measurement (ANA), sputum culture, alveolar lavage fluid bacterial culture, alveolar lavage fluid acid fast staining, and alveolar lavage fluid mNGS., Results: Chest CT: Cystic dilation of bronchi in both lungs, mainly in the lower lungs, with visible phlegm clots inside. Fibrobronchoscopy: A large amount of white foam like secretions can be seen in the lumens of the middle lobe of the right lung and the lower lobes of both lungs. Urinary routine (urine analysis + sediment quantification): protein+↑, occult blood+++. Urine Microprotein Determination//Urine Creatinine (Random Urine): Microalbumin 156.00 mg/L, Urine mALB/Urine Creatinine 132.73 mg/g; Quantitative determination of urine protein (24-hour urine): total protein 0.93 g/24-hour urine; Antinuclear antibody assay (ANA): weakly positive; Sputum bacterial culture: negative; Bacterial culture of bronchoalveolar lavage fluid: Mycobacterium abscess++, NGS in bronchoalveolar lavage fluid: Mycobacterium abscess. Clinical treatment plan: 0.25 g of azithromycin qd po+ 0.4 g of amikacin sulfate qd ivgtt+ 1 g cefmetazole sodium q12hours ivgtt. After 10 days of treatment, the patient improved and was discharged., Conclusions: This article reports a case of IgA nephropathy complicated with pulmonary abscess mycobacterial infection. Mycobacterium abscess was quickly and accurately identified by mNGS. Reasonable treatment measures were adopted clinically. The patient improved and was discharged. This study has important reference significance for the clinical diagnosis and treatment of Mycobacterium abscess infection. In addition, mNGS, as a novel detection method, has considerable prospects for rapid diagnosis of pathogens.

Rationale & Objective: Proteinuria is a surrogate end point for predicting long-term kidney outcomes in IgA nephropathy (IgAN) with levels<1g/day identified as a therapeutic target. However, this threshold has not been sufficiently studied. We quantified the associations of progression of IgAN with various levels of proteinuria., Study Design: Observational cohort study., Setting & Participants: 1,530 patients with IgAN and at least 12 months of follow-up at Peking University First Hospital., Exposure: Proteinuria levels updated over time (time-varying proteinuria, TVP)., Outcome: A composite kidney outcome of a 50% reduction in the estimated glomerular filtration rate or end-stage kidney disease., Analytical Approach: Marginal structural models., Results: After a median follow-up period of 43.5 (IQR, 27.2-72.8) months, 254 patients (16.6%) developed the composite kidney outcome. A graded association was observed between TVP and composite kidney outcomes with higher risk among those with proteinuria of≥0.5g/day. Compared with TVP<0.3g/day, the HRs for proteinuria levels of 0.3 to<0.5g/day, 0.5 to<1.0g/day, 1.0 to<2.0g/day, and≥2.0g/day were 2.22 (95% CI, 0.88-5.58), 4.04 (95% CI, 1.93-8.46), 8.46 (95% CI, 3.80-18.83), and 38.00 (95% CI, 17.62-81.95), respectively. The trend was more pronounced in patients with baseline proteinuria of≥1.0g/day, among whom a higher risk was observed with TVP of 0.3 to<0.5g/day compared with TVP<0.3g/day (HR, 3.26 [95% CI, 1.07-9.92], P=0.04). However, in patients with baseline proteinuria levels of<1g/day, the risk of composite kidney outcome only began to increase when TVP was≥1.0g/day (HR, 3.25 [95% CI, 1.06-9.90])., Limitations: Single-center observational study, selection bias, and unmeasured confounders., Conclusions: This study showed that patients with IgAN and proteinuria levels of>0.5g/day, have an elevated risk of kidney failure especially among patients with proteinuria levels≥1.0g/day before initiating treatment. These data may serve to inform the selection of proteinuria targets in the treatment of IgAN., Plain-Language Summary: The presence of proteinuria has often been considered a surrogate end point and a possible therapeutic target in clinical trials in IgA nephropathy (IgAN). Some guidelines recommend a reduction in proteinuria to<1g/day as a treatment goal based on the results of previous longitudinal studies. However, these findings may have been biased because they did not properly adjust for time-dependent confounders. Using marginal structural models to appropriately account for these confounding influences, we observed that patients with IgAN and proteinuria levels≥0.5g/day have an elevated risk of kidney failure, especially among patients who had proteinuria levels of≥1.0g/day before initiating treatment. These data may serve to inform the selection of proteinuria targets in the treatment of IgAN., (Copyright © 2024. Published by Elsevier Inc.)

In recent years, increasing numbers of reports have described new onset or active disease flare of IgA nephropathy (IgAN) during administration of TNF-α inhibitor (TNFi) therapy for chronic inflammatory diseases. Crohn's disease (CD) is the most common indication for TNFi therapy in this clinical setting, but the underlying etiology of IgAN in such patients remains unclear. We report our experience with three patients who developed acute worsening of preexisting urinalysis abnormalities and kidney dysfunction approximately 2 to 6 years after TNFi administration for CD. Kidney biopsies at the time of kidney disease flare revealed IgAN in two patients and IgAN complicated by acute tubulointerstitial nephritis in one patient. The CD and IgAN in all three patients were successfully managed with additional corticosteroid therapy and tonsillectomy without discontinuing TNFi therapy. The clinical course of our patients and similar patients described in the literature suggests that TNFi therapy for CD is associated with a relatively high risk for new onset or disease flare of IgAN. This report discusses the possible involvement of Th1/Th2 imbalance on the immunological background of CD or IgAN., (© 2023. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

Background: Previously, several studies have indicated that pediatric IgA nephropathy (IgAN) might be different from adult IgAN, and treatment strategies might be also different between pediatric IgAN and adult IgAN., Methods: We analyzed two prospective cohorts established by pediatric and adult nephrologists, respectively. A comprehensive analysis was performed investigating the difference in clinical and pathological characteristics, treatment, and prognosis between children and adults with IgAN., Results: A total of 1015 children and 1911 adults with IgAN were eligible for analysis. More frequent gross hematuria (88% vs. 20%, p < 0.0001) and higher proteinuria (1.8 vs. 1.3 g/d, p < 0.0001) were seen in children compared to adults. In comparison, the estimated glomerular filtration rate (eGFR) was lower in adults (80.4 vs. 163 ml/min/1.73 m 2 , p < 0.0001). Hypertension was more prevalent in adult patients. Pathologically, a higher proportion of M1 was revealed (62% vs. 39%, p < 0.0001) in children than in adults. S1 (62% vs. 28%, p < 0.0001) and T1-2 (34% vs. 8%, p < 0.0001) were more frequent in adults. Adjusted by proteinuria, eGFR, and hypertension, children were more likely to be treated with glucocorticoids than adults (87% vs. 45%, p < 0.0001). After propensity score matching, in IgAN with proteinuria > 1 g/d, children treated with steroids were 1.87 (95% CI 1.16-3.02, p = 0.01) times more likely to reach complete remission of proteinuria compared with adults treated with steroids., Conclusions: Children present significantly differently from adults with IgAN in clinical and pathological manifestations and disease progression. Steroid response might be better in children., (© 2024. The Author(s).)

Background and Objectives: Systemic-inflammation-based prognostic scores and hematological indices have shown value in predicting outcomes in various clinical settings. However, their effectiveness in predicting outcomes specifically for IgA nephropathy (IgAN) and membranous nephropathy (MN), the most common primary glomerular diseases diagnosed by kidney biopsy, has not been thoroughly investigated. Materials and Methods: We conducted a retrospective, observational study involving 334 adult patients with biopsy-proven IgAN (196 patients) and MN (138 patients) from January 2008 to December 2017 at a tertiary center. We assessed six prognostic scores [Glasgow prognostic score (GPS), modified GPS (mGPS), prognostic nutritional index (PNI), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-C-reactive protein ratio (LCRP)] and two hematological indices [red blood cell distribution width (RDW), platelet distribution width (PDW)] at diagnosis and examined their relationship with kidney and patient survival. Results: End-stage kidney disease (ESKD) occurred more frequently in the IgAN group compared to the MN group (37% vs. 12%, p = 0.001). The mean kidney survival time was 10.7 years in the IgAN cohort and 13.8 years in the MN cohort. After adjusting for eGFR and proteinuria, lower NLR and higher LCRP were significant risk factors for ESKD in IgAN. In the MN cohort, no systemic-inflammation-based scores or hematological indices were associated with kidney survival. There were 38 deaths (19%) in the IgAN group and 29 deaths (21%) in the MN group, showing no significant difference in mortality rates. The mean survival time was 13.4 years for the IgAN group and 12.7 years for the MN group. In the IgAN group, a lower PLR was associated with a higher mortality after adjusting for age, the Charlson comorbidity score, eGFR, and proteinuria. In patients with MN, higher NLR, PLR, and RDW were associated with increased mortality. Conclusions: NLR and LCRP are significant predictors of ESKD in IgAN, while PLR is linked to increased mortality. In MN, NLR, PLR, and RDW are predictors of mortality but not kidney survival. These findings underscore the need for disease-specific biomarkers and indicate that systemic inflammatory responses play varying roles in the progression and outcomes of these glomerular diseases. Future studies on larger cohorts are necessary to validate these markers.