Clonal hematopoiesis of indeterminate potential is associated with acute kidney injury

Caitlyn Vlasschaert, Cassianne Robinson-Cohen, Jianchun Chen, Elvis Akwo, Alyssa C. Parker, Samuel A. Silver, Pavan K. Bhatraju, Hannah Poisner, Shirong Cao, Ming Jiang, Yinqiu Wang, Aolei Niu, Edward Siew, Joseph C. Van Amburg, Holly J. Kramer, Anna Kottgen, Nora Franceschini, Bruce M. Psaty, Russell P. Tracy, Alvaro AlonsoDan E. Arking, Josef Coresh, Christie M. Ballantyne, Eric Boerwinkle, Morgan Grams, Ming Zhi Zhang, Bryan Kestenbaum, Matthew B. Lanktree, Michael J. Rauh, Raymond C. Harris, Alexander G. Bick

Research output: Contribution to journalArticlepeer-review


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 Jak2V617F-CHIP in two mouse models of AKI. In both models, CHIP was associated with more severe AKI, greater renal proinflammatory macrophage infiltration and greater post-AKI kidney fibrosis. In summary, this work establishes CHIP as a genetic mechanism conferring impaired kidney function recovery after AKI via an aberrant inflammatory response mediated by renal macrophages.

Original languageEnglish (US)
Pages (from-to)810-817
Number of pages8
JournalNature medicine
Issue number3
StatePublished - Mar 2024

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology


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