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Background and Aim: To understand the clinical and pathological characteristics of patients with IgA nephropathy (IgAN) complicated by hyperuricemia, and to analyze the time-averaged SUA (TA-SUA) on the prognosis of IgAN., Methods and Results: A retrospective analysis of 718 IgAN patients with diagnosis confirmed by renal biopsy and follow-up of more than 1 year was performed. At least two serum uric acid (SUA) levels were measured at intervals of 0.5-1 year during follow-up. The TA-SUA was calculated according to the area under the curve during the follow-up period. The primary endpoint of the study was the doubling of creatinine or end-stage renal disease. Four groups (Q1-Q4) were divided according to TA-SUA quartile spacing from low to high, and the association of the TA-SUA with prognosis in IgAN patients was assessed using Kaplan-Meier survival analysis and Cox proportional hazards models. This study included 718 patients with IgAN, of whom 181 (25.21 %) had hyperuricemia.Compared with the other three groups, the clinical and pathological characteristics of patients in the fourth quarter were more severe in both baseline SUA and TA-SUA groups. Multivariate results suggested that baseline SUA was not an independent risk factor for renal prognosis in IgAN patients after adjustment for clinical variables such as eGFR. High TA-SUA is an independent risk factor for renal prognosis in IgAN patients., Conclusions: Hyperuricemia is common in IgA nephropathy.High TA-SUA in IgAN patients show more severe clinical features and pathological damage. TA-SUA is an independent risk factor for renal prognosis in IgA nephropathy patients., Competing Interests: Conflict of interest statement The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Hypothesis: KDIGO recommends proteinuria <1 g/d as a treatment target in patients with immunoglobulin A nephropathy (IgAN) because of high risk of progression to kidney failure. However, long-term kidney outcomes in patients with low-grade proteinuria remain insufficiently studied., Methods: We enrolled patients with biopsy-proven primary IgAN from the Swedish Renal Registry and analyzed associations between urine albumin-to-creatinine ratio (uACR, in categories <0.3, 0.3-0.5, 0.5-1.0, 1.0-1.5, 1.5-2.0, and ≥2.0 g/g) and the occurrence of major adverse kidney events [MAKE, a composite of kidney replacement therapy (KRT) and >30% decline in estimated glomerular filtration rate (eGFR)]. We also explored the risk of kidney events associated with change in uACR within a year., Results: We included 1269 IgAN patients (74% men, median 53 years, mean eGFR 33 ml/min/1.73 m², median uACR 0.7 g/g). Over a median follow-up of 5.5 [2.8; 9.2] years, 667 MAKE and 517 KRT events occurred, and 528 patients experienced >30% eGFR decline. Compared with uACR < 0.3 g/g, any higher uACR category was strongly and incrementally associated with the risk of MAKE [adjusted hazard ratios (HR) ranging from 1.56 (95%CI 1.14-2.14) if uACR 0.3-0.5 g/g to 4.53 (3.36-6.11) if uACR ≥ 2.0 g/g], KRT (HR ranging from 1.39 to 4.65), and eGFR decline >30% (HR ranging from 1.76 to 3.47). In 785 patients who had repeated uACR measurements within a year, and compared with stable uACR, the risk of kidney events was lower if uACR decreased by 2-fold (HR ranging from 0.47 to 0.49), and higher if uACR increased by 2-fold (HR from 1.18 to 2.56), irrespective of baseline uACR., Conclusions: There is substantial risk of adverse kidney outcomes among patients with IgAN and uACR between 0.3 and 1.0 g/g, a population currently considered at low risk of CKD progression. Reduction in uACR is associated with better kidney outcomes, irrespective of baseline uACR., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

IgA nephropathy and IgA vasculitis with nephritis, albeit rare, represent two relatively frequent glomerular conditions in childhood. Compared to adults, pediatric IgA nephropathy has a more acute presentation, most frequently with synpharyngitic macrohematuria and histologically with more intense inflammation and less intense chronic damage. Management of these conditions is controversial and supported by little high-quality evidence. The paucity of evidence is due to the disease heterogeneity, its inter-ethnic variability, and the difficulty of extrapolating data from adult studies due to the peculiarities of the condition in children. IgA vasculitis with nephritis is a kidney manifestation of a systemic disorder, typical of the pediatric age, in which both the diagnosis of kidney involvement and its management are poorly defined, and an interdisciplinary approach is crucial. Both conditions can have a profound and long-lasting impact on kidney function and the global health of affected children. The International Pediatric Nephrology Association has therefore convened a diverse international group of experts from different disciplines to provide guidance on the recommended management of these conditions in children and to establish common definitions and define priorities for future high-quality, evidence-based collaborative studies for the benefit of children., Competing Interests: Declarations. Competing interests: MV has participated in sponsored trials and has received speaker/consultant fees from Alexion, Apellis, Bayer, Roche, Chinook, Novartis, Travere, Glaxo, Vifor, Biocryst, and PureSpring. These did not influence the content of this guideline. SS has no conflict of interest to declare. RC has no conflict of interest to declare. JB reports research grants from Argenx, Calliditas Therapeutics, Chinook Therapeutics, Galapagos, GlaxoSmithKline, Novartis, and Travere Therapeutics and is medical and/or scientific advisor to Alnylam Pharmaceuticals, Argenx, Astellas Pharma, BioCryst Pharmaceuticals, Calliditas Therapeutics, Chinook Therapeutics, Dimerix, Galapagos, Novartis, Omeros, Travere Therapeutics, UCB, Vera Therapeutics, and Visterra. MBF holds Advisor-Speaker contracts with Natera and Sanofi Pharmaceutical. DH has no conflicts of interest to declare. KG reports consultative roles with Travere Inc. and research support from Travere Inc., Roche Inc., and Aurinia Inc. MH has received consulting fees from Argenx, AstraZeneca, CareDx, Novartis, Travere, and Vera Therapeutics. MAAH has no conflict of interest to disclose. MA is a member of advisory boards and participates in scientific events receiving honoraria from Alexion and Gador. This did not influence the content of this guideline. PB has no conflict of interest to declare. SK has no conflict of interest to declare. ILD has no conflict of interest to declare. ZHL has no conflict of interest to declare. MM has no conflict of interest to declare. YS has no conflict of interest to disclose. MS has no conflict of interest to declare. QS has no conflict of interest to declare. HT has no conflict of interest to declare. DH has no conflict of interest to declare. EH has no conflict of interest to declare. KP has no conflict of interest to declare. AA has no conflict of interest to declare. OB has participated in sponsored trials and has received speaker/consultant fees from Alexion, Alnylam, Biocodex, Novartis, PureSpring, Travere, and Vifor. These did not influence the content of this guideline. KN has participated in sponsored trials and has received speaker/consultant fees from AstraZeneca, Alexion, KyowaKirin, Novartis, Sumitomo Pharma, and Chugai Pharmaceutical. These did not influence the content of this guideline., (© 2024. The Author(s).)

A single Raman spectrum reflects limited molecular information. Effective fusion of the Raman spectra of serum and urine source domains helps to obtain richer feature information. However, most of the current studies on immunoglobulin A nephropathy (IgAN) based on Raman spectroscopy are based on small sample data and low signal-to-noise ratio. If a multi-source data fusion strategy is directly adopted, it may even reduce the accuracy of disease diagnosis. To this end, this paper proposes a data enhancement and spectral optimization method based on variational autoencoders to obtain reconstructed Raman spectra with doubled sample size and improved signal-to-noise ratio. In the diagnosis of IgAN in multi-source domain Raman spectra, this paper builds a global and local feature decoupled variational autoencoder (DMSGL-VAE) model based on multi-source data. First, the statistical features after spectral segmentation are extracted, and the latent variables obtained by the variational encoder are decoupled through the decoupling module. The global representation and local representation obtained represent the global shared information and local unique information of the serum and urine source domains, respectively. Then, the cross-source reconstruction loss and decoupling loss are used to constrain the decoupling, and the effectiveness of the decoupling is proved quantitatively and qualitatively. Finally, the features of different source domains were integrated to diagnose IgAN, and the results were analyzed for important features using the SHapley Additive exPlanations algorithm. The experimental results showed that the AUC value of the DMSGL-VAE model for diagnosing IgAN on the test set was as high as 0.9958. The SHAP algorithm was used to further prove that proteins, hydroxybutyrate, and guanine are likely to be common biological fingerprint substances for the diagnosis of IgAN by serum and urine Raman spectroscopy. In summary, the DMSGL-VAE model designed based on Raman spectroscopy in this paper can achieve rapid, non-invasive, and accurate screening of IgAN in terms of classification performance. And interpretable analysis may help doctors further understand IgAN and make more efficient diagnostic measures in the future., Competing Interests: Declaration of competing interest The authors declare that they have no conflicting financial interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: IgA nephropathy (IgAN) exhibits an unpredictable trajectory, creating difficulties in prognostication, monitoring, treatment, and research planning. This study provides a comprehensive depiction of the progression of kidney function throughout the disease course, from diagnosis to a span of 36 years post-diagnosis., Methods: We utilized a cohort of 400 Norwegian IgAN patients, from diagnosis to the occurrence of death, initiation of kidney replacement therapy (KRT), or the latest follow-up. Recorded proteinuria (n = 2676) and creatinine (n = 8738) measurements were retrieved. Patients were divided into subgroups based on their specific estimated glomerular filtration rate (eGFR) slopes., Results: Median follow-up was 16 years. During this period, 34% of patients either died or initiated KRT. Among patients who reached endpoint, the median duration from diagnosis to the initiation of KRT or death was 8 years. Notably, 34% of the cohort exhibited a stable disease course, characterized by an eGFR decline of less than 20% between two consecutive measurements. Differences in subsequent disease trajectories among two subgroups with similar eGFR levels at diagnosis could not be accounted for by variations in treatment strategies. Among patients with proteinuria < 1 g/24 h in less than half of the measurements, KRT was five times more prevalent compared to those with more than half of the measurements recording proteinuria < 1 g/24 h (p-value = 0.001)., Conclusions: While a significant proportion of IgAN patients reach kidney failure within their lifetimes, outcomes vary widely. Clinical data at diagnosis offer limited insights into long-term risks. Enhanced risk stratification necessitates data collection at multiple time points., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the Regional Ethics Committee of Western Norway (No. 2013/553). All the study participants provided informed consent. The research was done according to the Declaration of Helsinki. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

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).)

This study evaluated the diagnostic value of the automated UF-5000 parameters and compared it with that of aberrant erythrocytes and acanthocytes classified by microscopy for identifying IgA glomerular hematuria to propose a predictive model for clinical use. It also compared correlations between erythrocyte parameters and malformed erythrocytes. Urine samples from 53 biopsy-proven IgA hematuria cases and 143 non-IGA nephropathic hematuria cases as controls were analyzed. The ratio of small red blood cells to nonlysed red blood cells (UF-sRBC%) and lysed red blood cells (lysed RBCs) showed good diagnostic performance for IgA glomerular hematuria (area under the curve [AUC] = 0.857 [P = 0.000] and AUC = 0.860 [P = 0.000], respectively). Combining UF-sRBC%, lysed RBCs, and urine protein dry chemistry improved the diagnostic accuracy (AUC = 0.967; positive predictive value [PPV] = 91.89%; negative predictive value [NPV] = 93.10%; P = 0.000). This approach surpassed traditional microscopy for aberrant erythrocytes (AUC = 0.895; PPV = 62.27%; NPV = 88.66%; P = 0.008) and acanthocytes (AUC = 0.868; PPV = 72.97%; NPV = 83.65%; P = 0.006). The erythrocyte size index was negatively correlated with the proportion of urinary aberrant erythrocytes (r = - 0.787; P = 0.000). The UF-5000 erythrocyte parameters facilitate rapid identification of IgA nephropathy and could replace manual microscopy., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

An incidental finding in urine smears from a patient with a presumptive diagnosis of an IgA mesangial nephropathy is presented. A possible example of the potential value of urine cytology in functional renal disorders. We report a case of an incidental finding in urine cytology from a patient with a presumptive diagnosis of an IgA mesangial glomerulonephritis, previously diagnosed as atypical urothelial cells., (© 2024 John Wiley & Sons Ltd.)

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.)

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.)

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.)

The billing database of the universal healthcare system in Japan potentially includes large-cohort data of patients with immunoglobulin A nephropathy, diagnosis codes aimed at billing should not be directly used for clinical research because of the risk of misdiagnosis. To solve this problem, we aimed to develop a novel method for identifying patients with immunoglobulin A nephropathy from billing data using machine learning. The medical records and bills of 3,743 patients who consulted nephrologists at a single center were extracted. Patients were labeled to have been diagnosed with immunoglobulin A nephropathy through a review of medical records. A manual analysis of the diagnostic accuracy and machine learning was performed. For machine learning, the datasets were preprocessed in three patterns and assigned to the XGBoost program using five-fold cross-validation. Of all the participants, 437 were labeled as having been diagnosed with immunoglobulin A nephropathy. Bill codes for immunoglobulin A nephropathy were provided to approximately half of them. The manually created criteria consisting of the recommended examinations and treatments in the Japanese guidelines for immunoglobulin A nephropathy showed both specificity and sensitivity < 0.8. In contrast, with the receiver operating characteristic curve analysis, the machine learning process yielded area under the curve values over 0.9 with preprocessing from the clinical viewpoint. Applying machine learning technology to a dataset preprocessed from a clinical viewpoint achieved a high performance in detecting patients with immunoglobulin A nephropathy. This methodology contributes to the construction of a disease-specific cohort using big bill data., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Tsunoda et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: To investigate the prognosis and risk factors of IgA vasculitis nephritis (IgAVN) in children. Methods: A retrospective cohort study was conducted. Clinical data were collected from 264 children who were pathologically diagnosed with IgAVN at Department of Pediatric Nephrology, Tongji Hospital, affiliated with Tongji Medical College, Huazhong University of Science and Technology, between January 2011 and December 2017. All patients had a follow-up period of more than 3 years. Clinical characteristics, renal pathology, 3-year and 5-year prognosis were analyzed. The patients were grouped based on gender, age of onset (≤6 years, >6-9 years, and >9 years), pathological classification (≤Ⅲ and>Ⅲ),whether the prognosis was complete remission at 3 and 5 years. Independent sample t -tests, ANOVA or chi-squared test were used for intergroup comparisons. Spearman correlation analysis was applied for ordinal data, and multivariate Logistic regression was used to analyze factors affecting the prognosis. Receiver operating characteristic (ROC) curve was utilized to evaluate the predictive value of these factors. Results: Of the 264 children with IgAVN, 153 were male and 111 were female, the age of onset was 8.3 (6.7, 10.3) years, 118 patients (45%) with onset age >6-9 years accounted for the highest proportion. All patients presented with skin purpura and renal involvement, primarily manifesting as hematuria and/or proteinuria. Microscopic hematuria was observed in 253 patients (95.8%), while 246 patients (93.2%) showed proteinuria. In 256 patients (97.0%), hematuria or proteinuria urinalysis was detected within 6 months of skin purpura onset, and 243 patients (92.0%) underwent renal biopsy within 6 months of renal involvement. The most common clinical subtype in 264 IgAVN children was hematuria and proteinuria (204 cases, 77.3%), with grade Ⅲ being the predominant pathological classification (181 cases, 68.6%). Among children ≤6 years old, the 3-year complete remission rate was higher in males than in females (83.9% (26/31) vs. 7/16, χ ²=8.12, P =0.012). Factors independently associated with poor 5-year prognosis included time from hematuria or proteinuria urinalysis to renal biopsy >6 months, elevated serum cholesterol levels, and incomplete remission 3 years post-biopsy ( OR =5.41, 1.39, 6.02, 95% CI 1.40-20.86, 1.04-1.84, 2.61-13.88, all P <0.05). The serum cholesterol has a predictive value for 5-year prognosis ( P =0.020, AUC=0.62, 95% CI 0.52-0.71, Youden index=0.27, cutoff=4.37). Conclusions: For children with IgAVN aged≤6 years, the 3-year prognosis is better in males than in females. Time from hematuria or proteinuria urinalysis to renal biopsy >6 months, elevated serum cholesterol levels, and incomplete remission at 3 years post-biopsy may be independent risk factors for poor 5-year prognosis in children with IgAVN.

Background: The International IgA Nephropathy (IgAN) Network developed and validated two prognostic prediction models for IgAN, one incorporating a race parameter. These models could anticipate the risk of a 50% reduction in estimated glomerular filtration rate (eGFR) or progression to end-stage renal disease (ESRD) subsequent to an IgAN diagnosis via renal biopsy. This investigation aimed to validate the International IgA Nephropathy Prediction Tool (IIgANPT) within a contemporary Chinese cohort., Methods: Within this study,185 patients diagnosed with IgAN via renal biopsy at the Center for Kidney Disease, Second Affiliated Hospital of Nanjing Medical University, between January 2012 and December 2021, were encompassed. Each patient's risk of progression was assessed utilizing the IIgANPT formula. The primary outcome, a 50% decline in eGFR or progression to ESRD, was examined. Two predictive models, one inclusive and the other exclusive of a race parameter, underwent evaluation via receiver-operating characteristic (ROC) curves, subgroup survival analyses, calibration plots, and decision curve analyses., Results: The median follow-up duration within our cohort spanned 5.1 years, during which 18 patients encountered the primary outcome. The subgroup survival curves exhibited distinct separations, and the comparison of clinical and histological characteristics among the risk subgroups revealed significant differences. Both models demonstrated outstanding discrimination, evidenced by the areas under the ROC curve at five years: 0.882 and 0.878. Whether incorporating the race parameter or not, both prediction models exhibited acceptable calibration. Decision curve analysis affirmed the favorable clinical utility of both models., Conclusions: Both prognostic risk evaluation models for IgAN exhibited remarkable discrimination, sound calibration, and acceptable clinical utility.

Background: Kidney fibrosis is the common final pathway of virtually all advanced forms of chronic kidney disease (CKD) including diabetic nephropathy (DN), IgA nephropathy (IgAN) and membranous nephropathy (MN), with complex mechanism. Comparative gene expression analysis among these types of CKD may shed light on its pathogenesis. Therefore, we conducted this study aiming at exploring the common and specific fibrosis-related genes involved in different types of CKD., Methods: Kidney biopsy specimens from patients with different types of CKD and normal control subjects were analyzed using the NanoString nCounter® Human Fibrosis V2 Panel. Genes differentially expressed in all fibrotic DN, IgAN and MN tissues compared to the normal controls were regarded as the common fibrosis-related genes in CKD, whereas genes exclusively differentially expressed in fibrotic DN, IgAN or MN samples were considered to be the specific genes related to fibrosis in DN, IgAN and MN respectively. Quantitative real-time PCR (qRT-PCR) was performed to validate the expression of the selected genes., Results: Protein tyrosine phosphatase receptor type C (PTPRC), intercellular cell adhesion molecule-1 (ICAM1), vascular cell adhesion molecule-1 (VCAM1), interleukin 10 receptor alpha (IL10RA) and CC chemokine receptor 2 (CCR2) were identified as the potential common genes for kidney fibrosis in different types of CKD, while peroxisome proliferator-activated receptor alpha (PPARA), lactate oxidase (LOX), secreted phosphoprotein 1 (SPP1) were identified as the specific fibrosis-associated genes for DN, IgAN and MN respectively. qRT-PCR demonstrated that the expression levels of these selected genes were consistent with the NanoString analysis., Conclusions: There were both commonalities and differences in the mechanisms of fibrosis in different types of CKD, the commonalities might be used as the common therapeutic targets for kidney fibrosis in CKD, while the differences might be used as the diagnostic markers for DN, IgAN and MN respectively. Inflammation was highly relevant to the pathogenesis of fibrosis. This study provides further insight into the pathophysiology and treatment of fibrotic kidney disease.

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.

To investigate the potential clinical value of urinary exosomal (uE) miR-451a as a biomarker for IgAN, urinary exosomes were isolated from 40 patients with IgAN, 30 patients with primary renal diseases without IgA as disease controls (non-IgAN group) and 21 healthy controls (HCs). The expression of miR-451a within exosomes was examined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). uE miR-451a was significantly upregulated in patients with IgAN compared to non-IgAN and HCs. The uE miR-451a level was positively correlated with the change in eGFR and negatively correlated with serum creatinine, urinary macrophage migration inhibitory factor ( MIF), interleukin-6 (IL-6) and tumor necrosis factor (TNF-α). A dual-luciferase reporter assay confirmed that MIF was a direct target of miR-451a. Receiver operating characteristic (ROC) curve analysis revealed that the expression of uE miR-451a showed potential diagnostic value for IgAN. Additionally, the uE miR-451a level could distinguish patients with IgAN with mild tubular atrophy/interstitial fibrosis from those with severe tubular atrophy/interstitial fibrosis. After a mean follow-up of 14.2 months, the levels of eGFR loss (ml/min/1.73 m 2 /year) were negatively correlated with baseline miR-451a. The levels of baseline miR-451a in the complete remission group were significantly higher than those in the non-complete remission group. uE miR-451a expression was significantly elevated in patients with IgA nephropathy and may serve as a potential biomarker for the diagnosis of IgAN and evaluation of tubulointerstitial damage, while the baseline levels of uE miR-451a may be predictors of therapeutic efficacy and disease progression.

This study aims to explore the relationship between serum soluble interleukin-2 receptor alpha (sIL-2Rα) levels and histologic features in immunoglobin A nephropathy (IgAN), and evaluate its predicting values on disease progression and remission status. IgAN patients were included retrospectively. Lee classification, Oxford classification and histological scoring were evaluated. Patients' estimated filtration rate (eGFR) and proteinuria remission status were collected during 6-month follow-up. Logistic regression was used to determine the risk factors and predicting value. Receiver operating characteristic (ROC) curve were used to determine the predicting value for outcome. One hundred seventy-two subjects were included in this study. Individuals in moderate-to-severe tubulointerstitial inflammatory cell infiltration group manifested with significantly elevated serum sIL-2Rα levels than those in non-to-mild group. Serum sIL-2Rα levels were positively correlated with infiltration scores. Serum sIL-2Rα was an independent risk factor for moderate-to-severe inflammatory cell infiltration [sIL-2Rα: OR 1.29 (1.015-1.640, p = 0.038)]. ROC curve analysis regarding predictive value for moderate-to-severe inflammatory cell infiltration of sIL-2Rα suggested area under curve was 0.859 (0.801-0.918, p = 0.000) when sIL-2Rα combined with eGFR < 60 mL/(min·1.73 m 2 ), 24-h proteinuria excretion > 1.0 g, and hemoglobin. It showed good sensitivity (71.6%) and specificity (87.6%). Additionally, sIL-2Rα levels at kidney biopsy were strong predictive factor for kidney function loss 6 months after kidney biopsy [OR 4.161 (1.013-17.088, p = 0.048)]. High serum sIL-2Rα was significantly associated with serious inflammatory cell infiltration in IgAN, and it showed strong predictive value for disease prognosis. Serum sIL-2Rα could be a useful noninvasive biomarker to evaluate the extent of histological injury and disease prognosis in IgAN., Competing Interests: Declarations. Ethical approval: This study procedures were reviewed and approved by the Ethics Committee of Zhongshan Hospital, Fudan University (approval number: B2021-067R), and in compliance with the ethical principles established in the Declaration of Helsinki. Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s).)

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.)

Bioinformatics analysis helps to understand the underlying mechanisms and adjust diagnostic and treatment strategies for immunoglobulin A nephropathy (IgAN) by screening gene expression datasets. We explored the biological function of IgAN, and established and validated a diagnostic model for IgAN using weighted gene co-expression network analysis. Using the GSE93798 and GSE37460 datasets, we performed differential expression analysis, Gene Oncology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, constructed a protein-protein network, and identified hub genes. A diagnostic model was built using a receiver operating characteristic curve, calibration plot, and decision curve analysis. Two Gene Expression Omnibus (GEO) datasets were integrated to screen 38 differentially expressed genes between patients with IgAN and normal kidney donors in glomerular samples. KEGG enrichment analysis showed that the differentially expressed genes were mainly enriched in the IL-17 and relaxin signaling pathways. We constructed a protein-protein interaction (PPI) network of differentially expressed genes using the STRING database and cross-compared it with the results of weighted gene correlation network analysis to screen out the top 10 key genes: FOS, EGR2, FOSB, NR4A1, BR4A3, FOSL1, NR4A2, ALB, CD53, C3AR1.We also found that the immune infiltration level was remarkably increased in IgAN tissues. We established a 5-gene panel diagnostic model (ACTA2, ALB, AFM, ALDH1L1, and ALDH6A1). The combined diagnostic ability was high, with the area under the curve (AUC) was 0.964. Based on these 5 genes, we also developed a risk-scoring evaluation system for individuals. The calibration plot indicated that the nomogram-predicted probability of nonadherence was highly correlated with actual diagnosed nonadherence, and the decision curve analysis indicated that patients had a relatively good net benefit. The model and gene expression were also validated using an external dataset. Our study provides directions for exploring the potential molecular mechanisms of IgAN as well as diagnostic and therapeutic strategies., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Clinical risk prediction models are being generated at an increasing rate. One important component is the identification of groups for whom such models might require recalibration to retain their desired performance. To this end, an update of the postbiopsy International IgA Nephropathy Prediction Tool for children has been published in this issue of Kidney International. We review the methods used and generalizability in practice, along with broader concepts in model development and application., (Copyright © 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

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.)

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.)

The pediatric International IgA Nephropathy (IgAN) Prediction Tool comprises two models with and without ethnicity and is the first method to predict the risk of a 30% decline in estimated glomerular filtration rate (eGFR) or kidney failure in children at the time of biopsy using clinical risk factors and Oxford MEST histology scores. However, it is unknown if the Prediction Tool can be applied after a period of observation post-biopsy. Using an international multi-ethnic cohort of 947 children with IgAN, 38% of whom were followed into adulthood, the Prediction Tool was updated for use one year after biopsy. Compared to the original pediatric Prediction Tool, the updated post-biopsy Prediction Tool had a better model fit with higher R 2 D (51%/50% vs 20%), significant increase in 4-year C-statistics (0.83 vs 0.73/0.69, ΔC 0.09 [95% confidence interval 0.07-0.10] and ΔC 0.14 [0.12-0.15]) and better 4-year calibration with lower integrated calibration indices (0.74/0.54 vs 2.45/1.01). Results were similar after internal validation and when the models were applied two years after biopsy. Trajectories of eGFR after a baseline one year post-biopsy were non-linear and those at higher predicted risk started with a lower eGFR and experienced a more rapid decline over time. In children, eGFR had a variable rate of increase until 15-18 years old and then decreased linearly with a more rapid decline in higher risk groups that was similar to young adults of comparable risk. Thus, the original pediatric Prediction Tool should be used in children at the time of biopsy, and the updated pediatric Prediction Tool should be used to re-evaluate risk one or two years after biopsy., (Copyright © 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Context.—: Galactose-deficient immunoglobulin A1 (Gd-IgA1) deposition in the renal mesangium plays a role in the pathogenesis of IgA nephropathy., Objective.—: To assess the serum Gd-IgA1 level in biopsy-proven IgA nephropathy cases at diagnosis and 3 months post treatment and its relation with histologic Oxford classification., Design.—: In this hospital-based prospective cohort study, 40 cases and 20 controls were enrolled. Serum samples of biopsy-proven IgA nephropathy cases collected on the day of biopsy and 3 months post treatment were evaluated. Solid-phase ELISA (enzyme-linked immunosorbent assay) was performed for assessment of Gd-IgA1 level. All renal biopsies were scored by using the Oxford classification (C-MEST score). The association of serum Gd-IgA1 levels with other established prognostic parameters was assessed. To estimate the prognostic value of markers, logistic regression analysis and Kruskal-Wallis ANOVA (analysis of variance) were used., Results.—: A significant difference was observed in the serum Gd-IgA1 level values in the IgA nephropathy cases and healthy controls (P = .001) at baseline. However, no significant correlation between serum Gd-IgA1 levels at baseline and 3 months of follow-up (P = .31) or between baseline levels and age, proteinuria, hematuria, or estimated glomerular filtration rate was noted. There was no significant correlation between C-MEST score and serum Gd-IgA1 levels at baseline (P > .05); however, the distribution of Gd-IgA1 at 3 months was found to differ significantly between different grades of S score (P = .008)., Conclusions.—: Serum Gd-IgA1 levels may be of utility in predicting disease progression in IgA nephropathy cases. Measurement of serum Gd-IgA1 levels for the diagnosis and prognosis of IgA nephropathy may preclude the need for invasive renal biopsies., Competing Interests: The authors have no relevant financial interest in the products or companies described in this article., (© 2024 College of American Pathologists.)

Background: Immunoglobin-IgA nephropathy (IgAN) stands as the most prevalent primary glomerulonephritis globally. Recently, several studies have mentioned the essential role of the autoimmune response as a mechanism causing Berger's disease, but it is not clear., Aim: The aims of the study was to assess the correlation between autoimmune competences and explain the roles of certain immune contents in the progression of disease., Material and Method: One hundred and fifty patients participated in the study, including 75 patients with Berger's disease and 75 healthy controls. The chemiluminescence immunoassay technique was employing to assess the level of autoantibodies, while nephelometry was utilizing to quantify the concentration of immunoglobin-related disease and complement proteins (C1q and C4). Simpler, blood smears were accustomed to diagnosing fragments of RBCs (schistocytes), and simple flow cytometry was used to enumerate red blood cells (RBCs) and platelets., Results: The current study revealed a significantly increased in the schistocytes and lower counts of RBCs in the patients compared to the control. Also, the results showed that the level of ANA, ANCA and dsDNA was highly significant (p < 0.001) in the patients (67.1 ± 2.5 ng/ml, 55.9 ± 12.0 ng/ml, 65.0 ± 2.0 ng/ml respectively) than the control (5.5 ± 0.30 ng/ml, 15.4 ± 1.0 ng/ml, 12.5 ± 0.22 ng/ml, respectively). Furthermore, IgM level was significantly no different (p = 0.755) in a patient (2.8 ± 0.19 ng/ml) compared to the control (2.5 ± 0.26 ng/ml). While the level of IgA and IgG was highly significant (p < 0.001) in the patient (10.3 ± 0.99 ng/ml and 11.6 ± 12 ng/ml respectively) compared to the control (4.2 ± 0.69 ng/ml and 2.8 ± 0.99 ng/ml respectively). Additionally, levels of C4 and C1q were a significantly increase in serum patients than the control group. However, there is a direct correlation between autoimmune antibodies and complement., Conclusion: There was a strong correlation between immune system components and blood factors, which was identified as a contributing factor in the development of Berger's disease., (Copyright © 2024 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)

Background: IgA nephropathy (IgAN) is the most common primary glomerular disease in chronic kidney disease (CKD), exhibiting significant heterogeneity in both clinical and pathological presentations. We aimed to explore the risk factors influencing short-term prognosis (≥90 days) and to construct a nomogram model for evaluating the risk of CKD progression in IgAN patients., Methods: Clinical and pathological data of patients diagnosed with IgAN through biopsy at two centers were retrospectively collected. Logistic regression was employed to analyze the training cohort dataset and identify the independent predictors to construct a nomogram model based on the final variables. The predictive model was validated both internally and externally, with its performance assessed using the area under the curve (AUC), calibration curves, and decision curve analysis., Results: Out of the patients in the modeling group, 129 individuals (41.6%) did not achieve remission following 3 months of treatment, indicating a high risk of CKD progression. A multivariate logistic regression analysis demonstrated that body mass index, urinary protein excretion, and tubular atrophy/interstitial fibrosis were identified as independent predictors for risk stratification. A nomogram model was formulated utilizing the final variables. The AUCs for the training set, internal validation set, and external validation set were 0.746 (95% confidence intervals (CI) [0.691-0.8]), 0.764 (95% CI [0.68-0.85]), and 0.749 (95% CI [0.65-0.85]), respectively. The validation of the subgroup analysis also demonstrated a satisfactory AUC., Conclusion: This study developed and validated a practical nomogram that can individually predict short-term treatment outcomes (≥90 days) and the risk of CKD progression in IgAN patients. It provides reliable guidance for timely and personalized intervention and treatment strategies., Competing Interests: The authors declare there are no competing interests., (©2024 Zhang et al.)

It has been reported that many people with psoriasis have been diagnosed with secondary IgA nephropathy (IgAN). However, the mechanisms behind the association between psoriasis and IgAN have not been well clarified. The connection between psoriasis and IgAN deserves deeper exploration. Mendelian randomization (MR) analysis would be employed to explore the link of causality between IgAN and psoriasis, psoriasis vulgaris, other and unspecified psoriasis, guttate psoriasis, and arthropathic psoriasis. Transcriptomic analyses were carried out against the Gene Expression Omnibus databases. We identified crosstalk genes through the analysis of Differentially expressed genes and weight gene co-expression network analysis. Functional annotations were enriched for these crosstalk genes. Subsequently, we established a protein-protein interaction network, and candidate genes would be discovered through the utilization of the MCODE and CytoHubba plug-in applications. Lastly, the predictive efficacy of these genes was examined via creating receiver operating characteristic curves. The MR analysis suggested that psoriasis vulgaris patients were at a higher risk for IgAN. [OR = 1.040, 95%CI (1.005,1.076), p = 0.026 < 0.05]. Additionally, arthropathic psoriasis may augment the incidence of IgAN [OR = 1.081, 95%CI (1.040-1.124), p < 0.01] in the European population. Through the analysis of DEGs and WGCNA, we identified 12 significant genes (NETO2, RRM2, SLAMF7, GBP1, KIF20A, CCL4, MMP1, IL1β, NDC80, CXCL9, C15orf48, GSTA3), which may be potential crosstalk genes between the two diseases. Then, the functional annotation results indicated that the crosstalk genes seemed primarily involved in immune and inflammatory responses. By establishing the PPI network, we further discovered that CXCL9, IL1β, CCL4, and MMP1 play a vital part in psoriasis and IgAN, and all have good diagnostic values. Our MR analysis provided evidence that genetic vulnerability to IgAN may be associated with an elevated risk of psoriasis vulgaris and arthropathic psoriasis respectively among Europeans. Doctors should be aware of these associations when patients with psoriasis present with renal dysfunction, especially those with psoriasis vulgaris and arthropathic psoriasis. Chronic inflammation, drug effects, and immunity may contribute to the generation and development of both diseases. IL1β, CXCL9, CCL4, and MMP1 may be core biomarkers for psoriasis and IgAN., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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.)

Patients diagnosed with IgA nephropathy (IgAN) commonly experience a substantial burden of symptoms encompassing both physical and psychological aspects. Presently, there's a dearth of standardized assessment tools to effectively gauge the extent of symptom burden in IgAN patients. Therefore, this study aims to devise an IgAN Symptom Assessment Tool that enables a comprehensive evaluation of patient symptom burden and their self-perceived severity. Employing a prospective observational design, this study conducted a survey among patients diagnosed with IgAN at a hospital in China. The research team formulated an IgAN Symptom Burden Assessment Scale and administered a questionnaire to gauge patient symptom burden. Severity assessment was conducted on a 5-point Likert scale, with higher scores indicating a more pronounced burden of symptoms. The finalized scale comprised 14 distinct symptom items, and the questionnaire survey garnered responses from 200 patients, achieving a 100% response rate. Statistical analysis unveiled that nearly all patients regarded these symptoms as prevalent and significantly impactful on their daily lives, resulting in a considerable burden. Notably, mild oliguria, moderate nasal congestion, bitter taste , throat discomfort, alongside severe manifestations such as muscle weakness, fatigue, and foamy urine, were frequently reported by patients. The findings underscore that a substantial proportion of IgAN patients grapple with a significant burden of symptoms, emphasizing the imperative for healthcare providers to prioritize symptom management and implement proactive measures to alleviate these challenges. This study presents an innovative tool tailored for evaluating symptom burden specifically in IgAN patients. Subsequent research should center on validating this tool within larger patient cohorts to optimize the efficacy of symptom management in this demographic., (© 2024. The Author(s).)

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).)

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.)

Worldwide adoption of the Oxford Classification of IgA nephropathy (IgAN) has enabled comparison of pathology data from clinicopathological studies in different regions of the world. It is apparent that the frequency of Oxford Classification MEST-C scores shows geographic variations. These in part reflect differences in the stage of disease at diagnosis, criteria for performing biopsies and inclusion in clinical studies, and pathologist reporting practice. However, there appears to be a true geographic difference in the frequency of glomerular inflammation and crescents with a 2-3 fold greater proportion of patients showing these changes in East Asia when compared to Europe and North America. This indicates that the pathology of IgAN is influenced by genetic background. Geographic differences in the pathology of IgAN might underly the reported differences in clinical presentation and outcome in different regions of the world, and has important implications for clinical trials and patient management., (© 2024 Asian Pacific Society of Nephrology.)

IgA nephropathy (IgAN) is considered the most common primary glomerulonephritis worldwide with a predilection for Asian-Pacific populations and relative rarity in those of African descent. Perhaps 20%-50% of patients progress to kidney failure. The pathogenesis is incompletely understood. Mesangial deposition of immune complexes containing galactose-deficient IgA1 complexed with anti-glycan IgG or IgA antibodies results in mesangial cell activation and proliferation, inflammatory cell recruitment, complement activation, and podocyte damage. Diagnosis requires a biopsy interpreted by the Oxford criteria. Additional pathologic features include podocytopathy, thrombotic microangiopathy, and C4d staining. Biomarkers predicting adverse outcomes include proteinuria, reduced GFR, hypertension, and pathology. Acceptable surrogate endpoints for therapeutic trials include ongoing proteinuria and rate of eGFR decline. The significance of persisting hematuria remains uncertain. The mainstay of therapy is supportive, consisting of lifestyle modifications, renin-angiotensin inhibition (if hypertensive or proteinuric), sodium-glucose-transporter 2 inhibition (if GFR reduced or proteinuric), and endothelin-receptor antagonism (if proteinuric). Immunosuppression should be considered for those at high risk after maximal supportive care. Corticosteroids are controversial with the most positive results observed in Chinese. They carry a high risk of serious side effects. Similarly, mycophenolate may be most effective in Chinese. Other immunosuppressants are of uncertain benefit. Tonsillectomy appears efficacious in Japanese. Active areas of investigation include B-cell inhibition with agents targeting the survival factors BAFF and APRIL and complement inhibition with agents targeting the alternate pathway (Factors B and D), the lectin pathway (MASP-2), and the common pathway (C3 and C5). Hopefully soon, the who and the how of immunosuppression will be clarified, and kidney failure can be forestalled., Competing Interests: EF is in the Speaker Bureau for Boehringer Ingelheim and Lilly. RG is in the Speaker Bureau for Travere and Astra Zeneca. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Filippone, Gulati and Farber.)

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.)

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).)

Rationale & Objective: Glomerular disorders have a highly variable clinical course, and biomarkers that reflect the molecular mechanisms underlying their progression are needed. Based on our previous work identifying plasminogen as a direct cause of podocyte injury, we designed this study to test the association between urine plasmin(ogen) (ie, plasmin and its precursor plasminogen) and end-stage kidney disease (ESKD)., Study Design: Multicenter cohort study., Setting & Participants: 1,010 patients enrolled in the CureGN Cohort with biopsy-proven glomerular disease (focal segmental glomerulosclerosis, membranous nephropathy, and immunoglobulin A nephropathy)., Predictors: The main predictor was urine plasmin(ogen) at baseline. Levels were measured by an electrochemiluminescent immunoassay developed de novo. Traditional clinical and analytical characteristics were used for adjustment. The ratio of urine plasmin(ogen)/expected plasmin(ogen) was evaluated as a predictor in a separate model., Outcome: Progression to ESKD., Analytical Approach: Cox regression was used to examine the association between urinary plasmin(ogen) and time to ESKD. Urinary markers were log 2 transformed to approximate normal distribution and normalized to urinary creatinine (Log 2 uPlasminogen/cr, Log 2 urinary protein/cr [UPCR]). Expected plasmin(ogen) was calculated by multiple linear regression., Results: Adjusted Log 2 uPlasminogen/cr was significantly associated with ESKD (HR per doubling Log 2 uPlasminogen/cr 1.31 [95% CI, 1.22-1.40], P<0.001). Comparison of the predictive performance of the models including Log 2 uPlasminogen/cr, Log 2 UPCR, or both markers showed the plasmin(ogen) model superiority. The ratio of measured/expected urine plasmin(ogen) was independently associated with ESKD: HR, 0.41 (95% CI, 0.22-0.77) if ratio<0.8 and HR 2.42 (95% CI, 1.54-3.78) if ratio>1.1 (compared with ratio between 0.8 and 1.1)., Limitations: Single plasmin(ogen) determination does not allow for the study of changes over time. The use of a cohort of mostly white patients and the restriction to patients with 3 glomerular disorders limits the external validity of our analysis., Conclusions: Urinary plasmin(ogen) and the ratio of measured/expected plasmin(ogen) are independently associated with ESKD in a cohort of patients with glomerular disease. Taken together with our previous experimental findings, urinary plasmin(ogen) could be a useful biomarker in prognostic decision making and a target for the development of novel therapies in patients with proteinuria and glomerular disease., Plain-Language Summary: Glomerular diseases are an important cause of morbidity and mortality in patients of all ages. Knowing the individual risk of progression to dialysis or transplantation would help to plan the follow-up and treatment of these patients. Our work studies the usefulness of urinary plasminogen as a marker of progression in this context, since previous studies indicate that plasminogen may be involved in the mechanisms responsible for the progression of these disorders. Our work in a sample of 1,010 patients with glomerular disease demonstrates that urinary plasminogen (as well as the ratio of measured to expected plasminogen) is associated with the risk of progression to end-stage kidney disease. Urine plasminogen exhibited good performance and, if further validated, could enable risk stratification for timely interventions in patients with proteinuria and glomerular disease., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: C4d mesangial deposition, a hallmark of lectin pathway activation in immunoglobulin A nephropathy (IgAN), has been shown to be associated with risk of kidney failure. To date, the relationship between urinary C4d and renal outcome remain unelucidated., Methods: A total of 508 patients with biopsy-proven IgAN were enrolled in this study, whose baseline urine samples at the time of biopsy were collected and the levels of urinary C4d were quantified by enzyme-linked immunosorbent assay. The time-averaged C4d (TA-C4d) and the change in proteinuria were measured in sequential urine samples obtained from IgAN patients. The kidney progression event was defined as a 50% estimated glomerular filtration rate (eGFR) decline or end-stage kidney disease or death., Results: After a median follow-up of 36 months, 70 (13.8%) of the participants reached the kidney progression event. Higher levels of urinary C4d/Ucr were found to be associated with decreased eGFR, massive proteinuria, lower serum albumin levels, hypertension, and severe Oxford E and T scores. Upon adjusting for traditional risk factors (including demographics, eGFR, proteinuria, hypertension, Oxford pathologic score and immunosuppressive therapy), elevated levels of urinary C4d/Ucr were independently associated with an increased risk of chronic kidney disease progression [adjusted hazard ratio (HR) per standard deviation increment of log-transformed C4d/Ucr: 1.46; 95% CI 1.04-2.06; P = .030]. In reference to the low C4d group, the risk of poor renal outcome increased for the high C4d group (adjusted HR 1.93; 95% CI 1.05-3.54; P = .033). Additionally, a low baseline C4d level was independently associated with a favorable proteinuria response to immunosuppressive therapy at 3 months (adjusted relative risk 2.20; 95% CI 1.04-4.63, P = .038)., Conclusion: The urinary C4d, serving as a non-invasive biomarker, is associated with the progression of IgAN and holds the potential to predict proteinuria response in this disease., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Introduction: IgA nephropathy is the leading cause of primary glomerulonephritis worldwide. The Oxford classification can predict IgA nephropathy prognosis through renal biopsy however its applicability to the Nepalese population remains unexplored. This study aimed to evaluate the MEST-C score and treatment response in patients with IgA nephropathy., Methods: This descriptive cross-sectional study was conducted at a tertiary care center from November 2021 to November 2022 after obtaining ethical approval [IRC-193(6-11)t2078/079]. Total population sampling was done. Fifty-two consenting patients aged 16 or older with confirmed IgA nephropathy were included, excluding those with liver disease or expected survival of less than six months. The study assessed the MEST-C score, demographic factors, and clinical parameters. Data analysis was done using Statistical Package of Social Sciences., Results: Among 52 patients with segmental glomerulosclerosis (S1), 11 (24.44%) achieved complete remission, 30 (66.67%) partial remission, and 5 (11.11%) progressed to end-stage renal disease. In those with tubular atrophy/interstitial fibrosis (T1), 1 (5.88%) achieved complete remission, 13 (76.47%) partial remission, and 4 (23.53%) progressed to end-stage renal disease. For glomerular crescents (C1), 9 (47.37%) achieved complete remission, 9 (47.37%) partial remission, and 1 (5.26%) progressed to end-stage renal disease. IFTA% of 0-25% had complete remission in 15 (46.88%). Among the two patients with IFTA% ≥50%, one (50%) developed end-stage renal disease and the other achieved partial remission., Conclusions: The S1 and T1/2 components of the MEST-C score had higher rates of partial remission and progression to end-stage renal disease, while other indices showed mixed results. The risk of failing to achieve complete increased with an IFTA of more than 25%.

Primary glomerulonephritis comprises several renal-limited diseases that can cause haematoproteinuria, chronic kidney disease, nephrosis and end stage kidney disease. The most common of these are IgA nephropathy (IgAN), primary membranous nephropathy (PMN), Focal Segmental Glomerulosclerosis (FSGS) and Minimal Change Disease (MCD). Although rare, these diseases cause a significant burden to health care systems, given the high cost of treating End Stage Kidney Disease (ESKD) with dialysis or transplantation. Until recently, the pathogenesis of primary gloerulonephritis has remained obscure. However, recent advances in understanding of how these diseases evolve has led to the introduction of novel therapeutic agents. Trials are underway or have recently completed that have huge implications for the standard of care for the primary glomerulonephritidies, and should dramatically reduce the number of patients who progress onto end stage kidney disease. This article reviews the international Kidney Disease Improving Global Outcomes (KDIGO) guidelines for the treatment of IgAN, PMN, FSGS and MCD, as well as recent research on pathogenesis and treatment.

Introduction: Anti-GBM diseases with IgA deposition in the mesangial region are rarely described.The factors influencing renal prognosis in patients with anti-GBM disease combined with mesangial IgA deposition are unknown., Methods: We searched the pathological reports of the First Affiliated Hospital of Zhengzhou University from 2015 to 2023 and found that a total of 72 patients with the anti-GBM disease and 25 patients combined with mesangial IgA deposition. We studied the clinical and pathological features, renal prognosis, and the factors affecting renal prognosis in patients with anti-GBM disease combined with mesangial IgA deposition., Results: Their median age was 44 years, and their age distribution was unimodal. The proportion of oliguria or anuria in patients with anti-GBM disease combined with mesangial IgA deposition was significantly lower than that in patients with classic anti-GBM disease (13.04 vs. 42.31%, p=0.030). Their 24-hour urinary protein excretion was significantly higher [median:3.25 vs. 1.12g/24h, Interquartile range(IQR):1.032~3.945 vs. 0.63~1.79g/24h, p=0.020], serum creatinine (SCr) level at the initial diagnosis was lower(median:456.0 vs. 825.5μmol/L, IQR:270.0~702.0 vs. 515.8~1231.2μmol/L, p=0.002), peak SCr level was lower (median: 601.0 vs. 907.2μmol/L, IQR: 376.5~937.0 vs. 607.0~1361.2μmol/L, p=0.007), and their serum complement 3(C3) level was higher(median: 1.275 vs. 1.015g/L, IQR:1.097~1.462 vs. 0.850~1.220g/L, p=0.027). They had better renal outcomes during follow-up (p<0.001). After adjustment for hypertension, oliguria or anuria, and crescents%, IgA deposition in the mesangial region was still an independent protective factor (p=0.003) for ESRD in anti-GBM patients. Hypertension (p=0.026) and SCr levels at initial diagnosis (p=0.004) were risk factors for renal prognosis in patients with anti-GBM disease combined with mesangial IgA deposition., Discussion: Patients with anti-GBM disease combined with mesangial IgA deposition have less severe renal impairment and better renal prognosis than patients with classic anti-GBM disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ning, Zhao, Liu, Qi and Zhao.)