Faculty, Staff and Student Publications

Language

English

Publication Date

3-1-2024

Journal

Nature Medicine

DOI

10.1038/s41591-024-02854-6

PMID

38454125

PMCID

PMC10957477

PubMedCentral® Posted Date

3-7-2024

PubMedCentral® Full Text Version

Post-print

Abstract

Age is a predominant risk factor for acute kidney injury (AKI), yet the biological mechanisms underlying this risk are largely unknown. Clonal hematopoiesis of indeterminate potential (CHIP) confers increased risk for several chronic diseases associated with aging. Here we sought to test whether CHIP increases the risk of AKI. In three population-based epidemiology cohorts, we found that CHIP was associated with a greater risk of incident AKI, which was more pronounced in patients with AKI requiring dialysis and in individuals with somatic mutations in genes other than DNMT3A, including mutations in TET2 and JAK2. Mendelian randomization analyses supported a causal role for CHIP in promoting AKI. Non-DNMT3A-CHIP was also associated with a nonresolving pattern of injury in patients with AKI. To gain mechanistic insight, we evaluated the role of Tet2-CHIP and Jak2

Keywords

Animals, Mice, Humans, Clonal Hematopoiesis, Hematopoiesis, Risk Factors, Aging, Acute Kidney Injury, Mutation

Published Open-Access

yes

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