Genome-wide DNA methylation analysis revealed epigenetic mechanism underlying end-stage renal disease

Abstract End-stage renal disease (ESRD) remains to be a major clinical challenge with persistently high morbidity and mortality, and its molecular mechanisms, particularly those shared among diverse primary kidney diseases during the progression to ESRD, have not been studied. Here we conducted a large-scale two-stage epigenome-wide association study of ESRD in two independent cohorts consisting of 704 controls and 1031 ESRD cases resulting from multiple kidney diseases. We identified 52 ESRD-associated differentially methylated CpG loci (DMLs) that showed consistent association effect between the two cohorts and across diverse kidney diseases. These 52 DMLs implicated 144 candidate genes that showed enrichment in calprotectin complex, RAGE receptor binding and herpes simplex virus 1 infection. Of the 52 DMLs, 5 DMLs were found to be associated with common complications of ESRD, and another 7 DMLs were also found to be associated with renal function decline in early-stage chronic kidney disease, demonstrating their potential as prognostic biomarkers for ESRD risk and related clinical complications. By identifying prognostic biomarkers and revealing the important roles of inflammation and immune dysregulation and renal fibrosis in renal progression to ESRD across diverse primary kidney diseases, our study has contributed greatly to improve clinical management and advance the development of novel therapies for ESRD.

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Publication Details

Journal
Nature Communications
Published
2026-08-03
DOI
https://doi.org/10.1038/s41467-026-76153-8
Primary Topic
Renal and Vascular Pathologies
Type
article
Field-Weighted Citation Impact
0.00

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article

Genome-wide DNA methylation analysis revealed epigenetic mechanism underlying end-stage renal disease

Zhiming Ye, Xueqing Yu, Ping Fu, Meng Wang et al.
Nature Communications
Renal and Vascular Pathologies
article

Genome-wide DNA methylation analysis revealed epigenetic mechanism underlying end-stage renal disease

Zhiming Ye, Xueqing Yu, Ping Fu, Meng Wang, Rajkumar Dorajoo, Wei Chen, Haiqiang Zhang, Resham L Gurung, Xiaohong Zhou, Jinghong Zhao, Dongying Fu, M Yiamunaa, Xin Jin, Jianjun Liu, Ling Wang, Min Li, Jihong Chen, Hua Gan, Jinjin Xu, Xiaojun Tan, Yaozhong Kong, Dianchun Shi, Lim yong su
article en

Abstract

Abstract End-stage renal disease (ESRD) remains to be a major clinical challenge with persistently high morbidity and mortality, and its molecular mechanisms, particularly those shared among diverse primary kidney diseases during the progression to ESRD, have not been studied. Here we conducted a large-scale two-stage epigenome-wide association study of ESRD in two independent cohorts consisting of 704 controls and 1031 ESRD cases resulting from multiple kidney diseases. We identified 52 ESRD-associated differentially methylated CpG loci (DMLs) that showed consistent association effect between the two cohorts and across diverse kidney diseases. These 52 DMLs implicated 144 candidate genes that showed enrichment in calprotectin complex, RAGE receptor binding and herpes simplex virus 1 infection. Of the 52 DMLs, 5 DMLs were found to be associated with common complications of ESRD, and another 7 DMLs were also found to be associated with renal function decline in early-stage chronic kidney disease, demonstrating their potential as prognostic biomarkers for ESRD risk and related clinical complications. By identifying prognostic biomarkers and revealing the important roles of inflammation and immune dysregulation and renal fibrosis in renal progression to ESRD across diverse primary kidney diseases, our study has contributed greatly to improve clinical management and advance the development of novel therapies for ESRD.

Nature Communications
BGI Group (China) (CN), Agency for Science, Technology and Research (SG), Army Medical University (CN), Sun Yat-sen University (CN), National University of Singapore (SG), Nanyang Technological University (SG), Sichuan University (CN), Khoo Teck Puat Hospital (SG), West China Hospital of Sichuan University (CN), First People's Hospital of Foshan (CN), Xinqiao Hospital (CN), Duke-NUS Medical School (SG), The First Affiliated Hospital, Sun Yat-sen University (CN), The Affiliated Yongchuan Hospital of Chongqing Medical University (CN), Kaiping Central Hospital (CN), Southern Medical University Shenzhen Hospital (CN), Guangdong Academy of Medical Sciences (CN), National University Health System (SG), Guangdong Provincial People's Hospital (CN), Signature Research (United States) (US), University of Chinese Academy of Sciences (CN), Southern Medical University (CN), Genome Institute of Singapore (SG), Chongqing Medical University (CN), South China University of Technology (CN)
Agency for Science, Technology and Research, National Natural Science Foundation of China, Natural Science Foundation of Guangdong Province, Guangdong Provincial People's Hospital, Medical Research Council, National Medical Research Council, National Key Research and Development Program of China
Openalex Percentile: Top 100%
Renal and Vascular Pathologies
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