Continental variations in IgA nephropathy among Asians

Prakash, Suma; Kanjanabuch, Talerngsak; Austin, Peter C.; Croxford, Ruth; Hsu, Chun-Shuo; Choi, An-Sook; Cattran, Dan

doi:10.5414/cnp70377

Cited by 16 publications

(10 citation statements)

References 22 publications

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“…7 , 8 , 9 , 10 , 11 , 12 Indian patients also seem to manifest the disease a decade earlier than Caucasian and East Asian patients. 13 , 14 A retrospective cohort study from our center reported hypertension in 52% and renal impairment in 32% of patients at presentation and only a 35% mean renal survival at 11 years, which is considerably less than that reported in studies of IgAN in Caucasian cohorts. 4 , 5 , 15 , 16 It is unclear whether these differences in epidemiology and risk of progression of IgAN in India are due to fundamental differences in the pathogenesis of IgAN or are more a reflection of differences in health care provision in different parts of the world.…”

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confidence: 66%

Epidemiology, baseline characteristics and risk of progression in the first South-Asian prospective longitudinal observational IgA nephropathy cohort

Schmeißer

Varughese

Franklin

et al. 2021

Kidney International Reports

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Introduction Glomerular Research And Clinical Experiments–IgA Nephropathy in Indians (GRACE-IgANI) is the first prospective South Asian IgAN cohort with protocolized follow-up and extensive biosample collection. Here we report the baseline clinical, biochemical, and histopathologic characteristics of GRACE IgANI and calculate baseline risk of progression for the cohort. Methods 201 incident adults with kidney biopsy–proven primary IgAN were recruited into GRACE-IgANI between March 2015 and September 2017. As of April 30, 2020, the cohort had completed a median follow-up of 30 months (interquartile range [IQR] 16-39). Results The commonest clinical presentation in GRACE IgANI was hypertension, with or without proteinuria, and nephrotic-range proteinuria was present in 34%, despite <10 months of lead time to kidney biopsy. The GRACE-IgANI kidney biopsy data demonstrated a disproportionate absence of active glomerular lesions and overrepresentation of segmental sclerosing lesions and tubulointerstitial fibrosis at presentation, often coexistent with relatively well-preserved estimated glomerular filtration rate (eGFR) and low levels of proteinuria, especially in males. Baseline risk of progression was calculated for each evaluable patient using 2 different risk prediction tools. The median 5-year absolute risk of end-stage kidney disease (ESKD) was 19.8% (IQR 2.7–57.4) and median 5-year risk of progression to the combined endpoint of 50% decline in eGFR or ESKD was 35.5% using the 2 tools. Conclusions The predicted risk of progression in this cohort was considerable. Over the next 5 years, we will dissect the pathogenic pathways that underlie this severe South Asian IgAN phenotype.

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confidence: 66%

Epidemiology, baseline characteristics and risk of progression in the first South-Asian prospective longitudinal observational IgA nephropathy cohort

Schmeißer

Varughese

Franklin

et al. 2021

Kidney International Reports

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“…IgAN became accepted as one of the commonest patterns of glomerular disease especially in younger males. By the 1980s, evidence emerged that IgAN may be even more common in North and East Asians than in European populations and is epidemiologically distinct, most notably in its equal distribution between genders in Asians [7], contrasted with the marked male dominance in Europeans. Caution may therefore be required when considering the relevance of genetic observations in Asians compared to European populations.…”

Section: Are ‘Genetic Factors' Important In Igan?mentioning

confidence: 99%

The Genetics of IgA Nephropathy: An Overview from Western Countries

Feehally

Barratt

2015

Kidney Dis

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Background: IgA nephropathy (IgAN) is the commonest primary glomerulonephritis worldwide and a significant cause of chronic kidney disease and end-stage renal disease. It is widely accepted that genetic factors play a role in the pathogenesis of IgAN. However, the identity of these genetic factors remains uncertain. Summary: Critical to all genetic studies is a precise phenotypic definition of the disease. It is well recognised that IgAN displays striking phenotypic variation, raising the possibility that it may not be a single disease and it may not be the same disease in different parts of the world. In this review, we discuss the challenges that this phenotypic variation poses to interpreting genetic data and the current evidence for specific gene involvement in IgAN, focusing particularly on data from European IgAN cohorts. Key Messages: With advances in genetic techniques, in particular next-generation sequencing, and an increased understanding of the importance of copy number variations, epigenetics and transcriptomics, it is likely that we will gain a greater understanding of the genetic basis for IgAN. However, due to the lack of consistency in epidemiological clinicopathological studies both within and between continents, this will only be achieved if we are able to more precisely phenotype IgAN populations. Facts from East and West: The reported prevalence of IgAN is higher in Asia than in Europe and North America. However, differences in use of biopsy for the diagnosis of IgAN should be taken into account in analysing data from both East and West. In Europe, IgAN affects men more frequently than women; this is not the case in Asia. Familial IgAN has been more frequently reported in Europe than in Asia. Within Europe, familial IgAN is more evident in southern than in northern populations. Changes in the pattern of serum IgA1 O-glycosylation is a common finding in IgAN patients in the East and West. SNPs within the gene coding for the enzyme C1GALT1 have been reported in Chinese and European patients. However, there is no evidence for a role of gene polymorphism of the C1GALT1 chaperone cosmc in Europeans. Genetic variants in the HLA gene family have been observed in populations from the East and West. Associations between IgAN and variants of the TAP1/PSMB and DEFA genes were observed in Asian but not in Western patients. Association with the angiotensin-converting enzyme gene was seen only in Asian patients.

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“…Retrospective studies from renal registries in India report that 30–40% of patients with IgAN have nephrotic syndrome and renal dysfunction at presentation 4 , 9 – 11 . Indian patients present with IgAN approximately over a decade earlier than Caucasian and East Asian patients, whose average age at presentation is 35–40 years 12 – 14 . These observations cannot be entirely attributed to differences in access to primary care and country-specific screening programs for kidney disease, and attest to the likelihood that IgAN may not be the same disease in different parts of the world.…”

Section: Introductionmentioning

confidence: 99%

Protocol and rationale for the first South Asian 5-year prospective longitudinal observational cohort study and biomarker evaluation investigating the clinical course and risk profile of IgA nephropathy: GRACE IgANI cohort

Schmeißer¹,

John²,

Korula³

et al. 2018

Wellcome Open Res

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Background: IgA nephropathy (IgAN) is the most common primary glomerulonephritis and an important cause of end-stage kidney disease. Unlike the slowly progressive course seen among Caucasian and East Asian subjects (actuarial survival 80-85% over 10 years), in India about 30-40% of patients have nephrotic syndrome and renal dysfunction at presentation and a 10-year renal survival of 35%, as reported from a retrospective registry. These observations cannot be entirely attributed to a lack of uniform screening protocols or late referral and attest to the probability that IgAN may not be the same disease in different parts of the world. Methods: We will prospectively recruit 200 patients with IgAN (the GRACE IgANI— Glomerular Research And Clinical Experiments- Ig A Nephropathy in Indians—cohort) and stratify them into low and high risk of progression based on published absolute renal risk scores. We will test the validity of this risk score in an unselected Indian IgAN population over a 5-year follow-up period. In parallel, we will undertake extensive exploratory serum, urine, renal and microbiome biomarker studies, firstly, to determine if the underlying pathogenic pathways are the same in Indian IgAN compared to those reported in Caucasian and East Asian IgAN. Secondly, we will systematically assess the value of measuring selected biomarkers and adding this data to traditional measures of risk in IgAN to predict kidney failure. We ultimately hope to generate a composite IgAN risk score specific for the Indian population. Ethics and data dissemination: Approval was obtained from the Institutional Review Board (Silver, Research and Ethics Committee) of the Christian Medical College, Vellore, India (Ref. No. IRB Min. No. 8962 [Other] dated 23.07.2014 and IRB Min. No. 9481 [Other] dated 24.06.2015). It is anticipated that results of this study will be presented at national and international meetings, with reports being published from late 2018.

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Continental variations in IgA nephropathy among Asians

Cited by 16 publications

References 22 publications

Epidemiology, baseline characteristics and risk of progression in the first South-Asian prospective longitudinal observational IgA nephropathy cohort

Epidemiology, baseline characteristics and risk of progression in the first South-Asian prospective longitudinal observational IgA nephropathy cohort

The Genetics of IgA Nephropathy: An Overview from Western Countries

Protocol and rationale for the first South Asian 5-year prospective longitudinal observational cohort study and biomarker evaluation investigating the clinical course and risk profile of IgA nephropathy: GRACE IgANI cohort

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