Dataset Information

IgA Nephropathy: A Chinese Perspective.

ABSTRACT:

Background

IgA nephropathy (IgAN) is the most common primary glomerular disease worldwide and remains a leading cause of chronic kidney disease and end-stage renal disease. The disease prevalence, clinical and pathological phenotypes, the underlying pathogenic molecular mechanisms, and the response to treatments are highly heterogeneous in different ethnic populations, which raise the concern that IgAN may differ across different parts of the world.

Summary

From a Chinese perspective, we stated the disease burden of IgAN, summarized genome-wide association studies and research into pathological molecules, and compared them with findings based on other populations. The emerging biomarkers, indigenous clinical trials, and major challenges for Chinese researchers and nephrologists in studying IgAN are also discussed.

Key messages

In this review, we described a higher risk of major susceptible loci in mucosal immunity, IgA production, and complement activation pathways in Chinese patients with IgAN. With our understanding of the pathogenesis of IgAN, novel biomarkers are emerging. Although there are challenges for conducting high-quality clinical trials in China, it is still feasible to conduct innovative and well-designed studies of IgAN. In the future, international collaborations on research infrastructure would be helpful to advance clinical and basic research in China.

SUBMITTER: Zhang Z

PROVIDER: S-EPMC9677733 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

IgA Nephropathy: A Chinese Perspective.

Zhang Zhao Z Zhang Yuemiao Y Zhang Hong H

Glomerular diseases 20211012 1

<h4>Background</h4>IgA nephropathy (IgAN) is the most common primary glomerular disease worldwide and remains a leading cause of chronic kidney disease and end-stage renal disease. The disease prevalence, clinical and pathological phenotypes, the underlying pathogenic molecular mechanisms, and the response to treatments are highly heterogeneous in different ethnic populations, which raise the concern that IgAN may differ across different parts of the world.<h4>Summary</h4>From a Chinese perspect ...[more]

PMID: 36751266

Similar Datasets

Project description:Purpose of the reviewImmunoglobulin A (IgA) nephropathy (IgAN) is the most common primary glomerular kidney disease. Children and adults are presumed to have the same disease and are treated similarly. However, there are differences between childhood IgAN and adult IgAN that may require unique treatment considerations, even after transition to adult nephrology services. A narrative review was conducted to compare childhood and adult IgAN and to describe the distinct characteristics of childhood IgAN. Reframing childhood IgAN can inform guideline recommendations unique to childhood IgAN, the development of targeted therapies, and clinical trial design.Sources of informationMedline and Embase were searched for reports on children and adults with IgAN published between January 2013 and December 2023 (updated May 2024). The search was not restricted by age group, outcomes reported, language, or study design. Randomized controlled trials (RCTs), observational studies, review articles, and nephrology conference abstracts were included. A total of 3104 reports were retrieved. Forty-seven reports (37 primary studies and 10 reviews) were included in the review. Two RCTs and 35 observational studies included a total of 45 085 participants (9223 children and 35 862 adults).MethodData were extracted for primary IgAN and not for IgA vasculitis-associated nephritis. Findings were described with no statistical comparisons due to variations in interventions and outcome definitions.Key findingsGross hematuria was the obvious clinical difference between childhood IgAN and adult (60-88% vs 15-20%). Nephrotic syndrome was more common in children, approaching up to 44%, while <18% of adults had nephrotic syndrome. Children were biopsied sooner (6 vs 15 months) and had more inflammatory kidney lesions (mesangial hypercellularity: 41-82% vs 38-64%; endocapillary hypercellularity: 39-58% vs 17-34%). Chronic kidney lesions were more prevalent in adults (segmental sclerosis: 62-77% vs 8-51%; interstitial fibrosis/tubular atrophy: 34-37% vs 1-18%). The use of immunosuppressive therapy was higher in children (46-84% vs 35-56%). Children were started on immunosuppressive therapy sooner than adults. Adults were more likely to be optimized with renin-angiotensin system inhibitors (87-94% vs 49-75%). Children had better kidney function than adults at diagnosis (estimated glomerular filtration rate of 90-128 vs 50-88 ml/min/1.73 m2), and children also had better kidney survival, with kidney failure of 3.1% vs 13.4% at 5 years. Children had more risk alleles for IgAN and higher levels of mannose-binding lectin than adults.LimitationsMost studies were retrospective and observational, with limited data on children and disease mechanisms. Data were not pooled for analysis because of important differences in definitions and measurements of baseline characteristics and outcomes. Data from countries with established urine screening programs were different compared to countries without urine screening programs. Some observed differences may be due to practice variation and delayed diagnosis in adults (lead-time bias). Well-designed prospective studies and standardized measures for kidney function assessment and outcomes can reduce heterogeneity and improve results from reviews.ConclusionInherent differences between childhood IgAN and adult IgAN may be due to distinct disease mechanisms. Approaching childhood IgAN as a separate condition could lead to the discovery of targeted therapies and improve management during childhood and after the transition to adult care.

Project description:The coexistence of immunoglobulin A nephropathy (IgAN) and idiopathic membranous nephropathy (IMN) in a few cases suggested that there could be existed a similar mechanism in pathogenesis of these two types of primary glomerulonephritis. In order to verify this hypothesis, a total of 23 reported IgAN-associated SNPs were genotyped in a cohort of 485 IMN patients and 569 healthy controls with Chinese Han origin. After Cochran-Armitage test for trend analysis, seven IgAN-associated SNPs located in the major histocompatibility complex (MHC) region were found to be significantly associated with the susceptibility of IMN, with rs9275596 as the top one (p = 1.97E-43, OR = 3.977). It was worth mentioning that the minor alleles of the SNPs conferred completely opposite effects on the pathogenesis of IMN and IgAN, suggesting quite different roles played by these SNPs for these two kinds of primary glomerulonephritis. Conditional logistic regression analysis displayed that SNPs protective from IMN (odds ratio < 1.00) were still significantly associated with IMN (p = 3.67E-4 for rs660895 and p = 1.26E-4 for rs9275224) with the most significant SNP rs9275596 as a covariate. Haplotype-based analysis showed that the seven SNPs were mapped to independent linkage disequilibrium (LD) blocks. Moreover, three out of these seven SNPs, including rs9275224, rs660895, and rs9357155, were found to be potential expression quantitative trait loci (eQTLs) for HLA-DQ molecules. Out of the purpose of identifying the causal variants for IMN within the MHC region, imputation analysis was performed using genotype data of Chinese Han released by the 1000 Genome Project and identified hundreds of SNPs potentially associated with the disease. In brief, our analysis revealed a significant association with the susceptibility of idiopathic membranous nephropathy for the IgAN-correlated SNPs. These SNPs conferred a completely different role for the pathogenesis of these two kinds of diseases.

Dataset Information

IgA Nephropathy: A Chinese Perspective.

Background

Summary

Key messages

Publications

IgA Nephropathy: A Chinese Perspective.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets