Summary
This international meta-analysis of epigenome-wide association studies identified 69 and 7 blood DNA methylation sites respectively linked to kidney function (eGFR) and kidney damage (UACR) across 33,605 and 15,068 participants. Several methylation associations at genes including JAZF1, PELI1, CHD2, PHRF1, LDB2, CSRNP1 and IRF5 were validated in kidney tissue or showed evidence of causal effects on kidney function. The findings suggest DNA methylation in blood may serve as an epigenetic biomarker for kidney disease risk and reveal pathways involving hemostasis, blood cell migration and immune activation.
UK applicability
These findings are potentially applicable to UK clinical practice as chronic kidney disease affects a significant proportion of the population. The identification of blood-based DNA methylation biomarkers could support early detection and risk stratification in UK kidney disease screening programmes, though validation in UK cohorts and clinical implementation studies would be required.
Key measures
Blood-based DNA methylation at CpG sites; estimated glomerular filtration rate (eGFR); urinary albumin-to-creatinine ratio (UACR); chronic kidney disease; albuminuria
Outcomes reported
The study identified 69 CpG sites where blood DNA methylation was associated with estimated glomerular filtration rate (kidney function) and 7 CpG sites associated with urinary albumin-to-creatinine ratio (kidney damage). These methylation associations showed directional consistency with clinical outcomes of chronic kidney disease and albuminuria.
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