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Emerging evidence on the role of clonal hematopoiesis of indeterminate potential in chronic kidney disease

Published:December 28, 2022DOI:https://doi.org/10.1016/j.trsl.2022.12.009

      Abstract

      Chronic kidney disease (CKD) was responsible for 1.2 million deaths globally in 2016. Despite the large and growing burden of CKD, treatment options are limited and generally only preserve kidney function. Characterizing molecular precursors to incident and progressive CKD could point to critically needed prevention and treatment strategies. Clonal hematopoiesis of indeterminate potential (CHIP) is typically characterized by the clonal expansion of blood cells carrying somatic mutations in specific driver genes. An age-related disorder, CHIP is rare in the young but common in older adults. Recent studies have identified causal associations between CHIP and atherosclerotic cardiovascular disease which are most likely mediated by inflammation, a hallmark of CKD. Animal evidence has supported causal effects of CHIP on kidney injury, inflammation, and fibrosis, providing impetus for human research. Although prospective epidemiologic studies investigating associations of CHIP with development and progression of CKD are few, intriguing findings have been reported. CHIP was significantly associated with kidney function decline and end stage kidney disease in the general population, although effect sizes were modest. Recent work suggests larger associations of CHIP with kidney disease progression in CKD patients, but further investigations in this area are needed. In addition, the accumulating literature has identified some heterogeneity in associations between CHIP and kidney endpoints across study populations, but reasons for these differences remain unclear. The current review provides an in-depth exploration into this nascent area of research, develops a conceptual framework linking CHIP to CKD, and discusses the clinical and public health implications of this work.

      Abbreviations:

      BP (blood pressure), CanPREDDICT (Canadian study of Prediction of Death, Dialysis, and Interim Cardiovascular evenTs), CHIP (Clonal hematopoiesis of indeterminate potential), CKD (Chronic kidney disease), CRIC (Chronic Renal Insufficiency Cohort), CVD (cardiovascular disease), EAA (epigenetic age acceleration), eGFR (estimated glomerular filtration rate), ESKD (end-stage kidney disease), GWAS (genome-wide association studies), IL (interleukin), MDS (myelodysplastic syndromes), MR (Mendelian randomization), RAAS (Renin-angiotensin-aldosterone system), TNF-α (tumor necrosis factor alpha), TOPMed (Trans-Omics for Precision Medicine program), uACR (urinary albumin-to-creatinine ratio), VAF (variant allele frequency)
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