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IgA Nephropathy Susceptibility Loci and Disease Progression.

ABSTRACT: BACKGROUND AND OBJECTIVES:At least 20 susceptibility loci of IgA nephropathy have been identified by genome-wide association studies to date. Whether these loci were associated with disease progression is unclear. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:We enrolled 613 adult patients with IgA nephropathy for a follow-up of ?12 months. All 20 IgA nephropathy susceptibility loci were selected and their tag single nucleotide polymorphisms (SNPs) were genotyped. After strict quality control, 16 SNPs and 517 patients with IgA nephropathy were eligible for subsequent analysis. Progression was defined as ESKD or 50% decrease in eGFR. A stepwise Cox regression analysis of all SNPs on Akaike information criterion was performed to select the best model. RESULTS:A four-SNP model, rs11150612 (ITGAM-ITGAX), rs7634389 (ST6GAL1), rs2412971 (HORMAD2), and rs2856717 (HLA-DQ/DR), was selected as the best predictive model. The genetic risk score calculated on the basis of the four SNPs was independently associated with disease progression before (hazard ratio [HR], 1.65; 95% confidence interval [95% CI], 1.29 to 2.12) and after adjustment by a recently reported clinical model (HR, 1.29; 95% CI, 1.03 to 1.62) or clinical-pathologic model (HR, 1.35; 95% CI, 1.03 to 1.77). Compared with low genetic risk, patients with middle genetic risk had a 2.12-fold (95% CI, 1.33 to 3.40) increase of progression risk, whereas patients with high genetic risk had 3.61-fold (95% CI, 2.00 to 6.52) progression risk increase. In addition, incorporation of genetic risk score could potentially increase discrimination of the clinical model (c-statistic increase from 0.83 to 0.86) or the clinical-pathologic model (c-statistic increase from 0.82 to 0.85) in predicting 5-year progression risk. CONCLUSIONS:The four-SNP genetic risk score was independently associated with IgA nephropathy progression and could enhance the performance of clinical and clinical-pathologic risk models.

SUBMITTER: Shi M

PROVIDER: S-EPMC6140573 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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IgA Nephropathy Susceptibility Loci and Disease Progression.

Shi Manman M Ouyang Yan Y Yang Mingxin M Yang Meng M Zhang Xiaoyan X Huang Wei W Wang Weiming W Wang Zhaohui Z Zhang Wen W Chen Xiaonong X Pan Xiaoxia X Ren Hong H Chen Nan N Xie Jingyuan J

Clinical journal of the American Society of Nephrology : CJASN 20180724 9

<h4>Background and objectives</h4>At least 20 susceptibility loci of IgA nephropathy have been identified by genome-wide association studies to date. Whether these loci were associated with disease progression is unclear.<h4>Design, setting, participants, & measurements</h4>We enrolled 613 adult patients with IgA nephropathy for a follow-up of ≥12 months. All 20 IgA nephropathy susceptibility loci were selected and their tag single nucleotide polymorphisms (SNPs) were genotyped. After strict qua ...[more]

PMID: 30042224

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Project description:ObjectiveWe aimed to explore the relationship between the presence and intensity of glomerular IgG deposition and the occurrence of kidney progression events in IgA nephropathy (IgAN).MethodsThis retrospective study encompassed a total of 1207 patients with IgAN spanning the period from 2010 to 2022, and complete follow-up data were accessible for 736 patients. The IgG intensity was categorized as follows: low-level, defined as IgG (±) and IgG (+), and high-level, defined as IgG (++) and IgG (+++).ResultsWe found that the IgG-positive deposited group (N = 113, 9.36%) had significantly higher levels of ESR, TC, LDL, uric acid, proteinuria, and blood glucose, and lower serum albumin level compared to the IgG-negative deposited group (N = 1094, 90.64%). In terms of pathology, the IgG-positive deposited group had a significantly higher percentage of T2 score compared to the IgG-negative deposited group (p = 0.002). At the end of the follow-up period, the IgG-positive deposited group had a higher eGFR decline (-5.7 ± 4.37 ml/year) compared to the IgG-negative deposited group (-4 ± 2.52 ml/year), however, there was not a statistically significant difference between the two groups (p = 0.096). We observed that the high-IgG group had significantly higher level of TG compared to the low-IgG group (p = 0.042). Further analysis revealed that the group of patients with high level of IgG deposition in the kidney experienced a higher incidence of composite kidney outcomes compared to the group with low level of IgG deposition (p = 0.009). Logistic regression analyses showed that high level IgG deposition was an independent risk factor for kidney progression of IgAN (HR 13.419; 95% CI 2.690-66.943, P = 0.029). Further analyses for a solid conclusion using Cox regression that we found high level IgG deposition (HR 115.277; 95% CI 2.299-5.779E3, P = 0.017), eGFR (HR 0.932; 95% CI 0.870-0.999, P = 0.047), and urine protein excretion (HR 1.001; 95% CI 1.000-1.002, P = 0.015) were independent risk factor for kidney progression of IgAN.ConclusionsThe intensity of IgG deposition has been found to be associated with the progression of IgAN. Future prospective studies should provide more robust evidence on the impact of IgG deposition on kidney outcomes in patients with IgAN.

Dataset Information

IgA Nephropathy Susceptibility Loci and Disease Progression.

Publications

IgA Nephropathy Susceptibility Loci and Disease Progression.

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