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)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: December 28, 2022
Accepted:
December 22,
2022
Received in revised form:
December 21,
2022
Received:
September 7,
2022
Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2022 Elsevier Inc. All rights reserved.
