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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\n                    <jats:italic>DNMT3A<\/jats:italic>\n                    , including mutations in\n                    <jats:italic>TET2<\/jats:italic>\n                    and\n                    <jats:italic>JAK2<\/jats:italic>\n                    . Mendelian randomization analyses supported a causal role for CHIP in promoting AKI. Non-\n                    <jats:italic>DNMT3A<\/jats:italic>\n                    -CHIP was also associated with a nonresolving pattern of injury in patients with AKI. To gain mechanistic insight, we evaluated the role of\n                    <jats:italic>Tet2<\/jats:italic>\n                    -CHIP and\n                    <jats:italic>Jak2<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>V617F<\/jats:italic>\n                    <\/jats:sup>\n                    -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.\n                  <\/jats:p>","DOI":"10.1038\/s41591-024-02854-6","type":"journal-article","created":{"date-parts":[[2024,3,7]],"date-time":"2024-03-07T06:06:27Z","timestamp":1709791587000},"page":"810-817","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":97,"title":["Clonal hematopoiesis of indeterminate potential is associated with acute kidney 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M.B.L. has received speaking and advisory board fees from Bayer, Otsuka, Reata and Sanofi, all unrelated to this work. S.A.S. has received speaking fees from Baxter, unrelated to this work. C.M.B. has received research funding, has consultancy agreements with or serves as a scientific advisor for Abbott Diagnostic, Akcea, Amgen, Esperion, Ionis, Novartis, Regeneron, Roche Diagnostic, Althera, Amarin, Arrowhead, AstraZeneca, Covidia, Denka Seiken, Esperion, Genentech, Gilead, Matinas BioPharma, New Amsterdam, Novo Nordisk, Pfizer, Roche Diagnostic and Sanofi-Synth\u00e9labo, all unrelated to this work. J. Chen reports having ownership interest in Health.io and having consultancy agreements with Health.io, Kaleido and Ultragenyx, all unrelated to this work. B.M.P. serves on the Steering Committee of the Yale Open Data Access Project funded by Johnson & Johnson, unrelated to this work. The other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}