Thickening of Glomerular Basement Membrane is Associated with Long-Term Prognosis in Patients with IgA Nephropathy.

IF 3 Q1 UROLOGY & NEPHROLOGY
Kidney360 Pub Date : 2025-09-16 DOI:10.34067/KID.0000000885
Fang Zhengying, Yang Mingxin, Wei Wenjie, Xu Jing, Du Wen, Chen Zijin, Ma Jun, Pan Xiaoxia, Wang Weiming, Ren Hong, Chen Nan, Ouyang Yan, Xie Jingyuan
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Abstract

Background: Glomerular basement membrane (GBM) ultrastructural abnormalities are common in IgAN, however, few studies have focused on clinical significance and prognostic value of GBM ultrastructural changes in IgAN patients.

Methods: A retrospective longitudinal cohort with 1006 biopsy-proven primary IgAN patients was collated. GBM thickness and texture of each case were assessed under transmission electron microscope. The primary end point was end stage renal disease (ESRD). Cox proportional hazards regression model was built to determine risk factors. Immunofluorescent staining was performed on patient kidney biopsy samples to validate the correlation between mesangial proliferation and abnormal GBM thickness. Twenty SNPs independently associated with IgAN in previous genome-wide association studies were genotyped in 617 patients and whole exome sequencing was performed in 56 patients to investigate potential variants underlying GBM ultrastructural changes.

Results: Of 1006 patients, 52% were female, and the mean age was 37.3±12.3 years old. Among all patients, 80 (8%) had abnormal thickness of GBM including 29 (3%) thickening of GBM and 51 (5%) thinning of GBM. Abnormal GBM texture was found in 25 (2%) patients. During a mean follow-up time of 46.4 months, 91 (9%) patients progressed to ESRD. By Cox regression analyses, we demonstrated that thickening of GBM at biopsy increased the risk of ESRD before (HR, 3.64, 95%CI, 1.47-7.55) and after adjusted by Oxford Scoring (HR, 2.92, 95%CI, 1.12-6.48) or international risk-prediction tool in IgA nephropathy (HR, 3.51, 95%CI, 1.41-7.29). Relevance analyses showed GBM thickening was positively correlated to mesangial hyperplasia and proliferation, but not genetic variants in IgAN patients.

Conclusions: Thickening of GBM correlated with mesangial hyperplasia and proliferation was associated with ESRD in IgAN patients, demonstrating the potential of incorporating ultrastructural changes into the pathological evaluation system of IgAN.

IgA肾病患者肾小球基底膜增厚与长期预后相关
背景:肾小球基底膜(Glomerular basal membrane, GBM)超微结构异常在IgAN中很常见,但很少有研究关注IgAN患者肾小球基底膜超微结构改变的临床意义和预后价值。方法:对1006例经活检证实的原发性IgAN患者进行回顾性纵向队列研究。透射电镜下观察各组基底膜的厚度和织构。主要终点为终末期肾病(ESRD)。建立Cox比例风险回归模型确定危险因素。对患者肾活检样本进行免疫荧光染色,以验证肾小球系膜增殖与异常GBM厚度之间的相关性。在之前的全基因组关联研究中,对617例患者进行了与IgAN独立相关的20个snp基因分型,并对56例患者进行了全外显子组测序,以研究GBM超微结构变化的潜在变异。结果:1006例患者中,女性占52%,平均年龄37.3±12.3岁。在所有患者中,80例(8%)患者存在GBM厚度异常,其中29例(3%)GBM增厚,51例(5%)GBM变薄。25例(2%)患者发现GBM质地异常。在平均46.4个月的随访期间,91例(9%)患者进展为ESRD。通过Cox回归分析,我们发现活检时GBM增厚增加了IgA肾病患者发生ESRD的风险(HR, 3.64, 95%CI, 1.47-7.55)以及经牛津评分(HR, 2.92, 95%CI, 1.12-6.48)或国际风险预测工具(HR, 3.51, 95%CI, 1.41-7.29)校正后的风险。相关分析显示,在IgAN患者中,GBM增厚与系膜增生和增殖呈正相关,但与遗传变异无关。结论:与系膜增生和增殖相关的GBM增厚与IgAN患者ESRD相关,显示了将超微结构变化纳入IgAN病理评价体系的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Kidney360
Kidney360 UROLOGY & NEPHROLOGY-
CiteScore
3.90
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0.00%
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