학술논문
Clonal hematopoiesis of indeterminate potential is associated with acute kidney injury.
Document Type
Academic Journal
Author
Vlasschaert C; Department of Medicine, Queen's University, Kingston, Ontario, Canada.; Robinson-Cohen C; Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt O'Brien Center for Kidney Disease, Vanderbilt University Medical Center, Nashville, TN, USA.; Chen J; Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt O'Brien Center for Kidney Disease, Vanderbilt University Medical Center, Nashville, TN, USA.; Akwo E; Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt O'Brien Center for Kidney Disease, Vanderbilt University Medical Center, Nashville, TN, USA.; Parker AC; Division of Genetic Medicine, Department of Medicine, School of Medicine, Vanderbilt University, Nashville, TN, USA.; Silver SA; Department of Medicine, Queen's University, Kingston, Ontario, Canada.; Bhatraju PK; Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington, Seattle, WA, USA.; Poisner H; Division of Genetic Medicine, Department of Medicine, School of Medicine, Vanderbilt University, Nashville, TN, USA.; Cao S; Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt O'Brien Center for Kidney Disease, Vanderbilt University Medical Center, Nashville, TN, USA.; Jiang M; Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt O'Brien Center for Kidney Disease, Vanderbilt University Medical Center, Nashville, TN, USA.; Wang Y; Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt O'Brien Center for Kidney Disease, Vanderbilt University Medical Center, Nashville, TN, USA.; Niu A; Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt O'Brien Center for Kidney Disease, Vanderbilt University Medical Center, Nashville, TN, USA.; Siew E; Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt O'Brien Center for Kidney Disease, Vanderbilt University Medical Center, Nashville, TN, USA.; Van Amburg JC; Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt O'Brien Center for Kidney Disease, Vanderbilt University Medical Center, Nashville, TN, USA.; Kramer HJ; Departments of Public Health Sciences and Medicine, Loyola University Chicago, Maywood IL, USA.; Kottgen A; Institute of Genetic Epidemiology, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany.; Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.; Franceschini N; Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA.; Psaty BM; Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology and Health Systems and Population Health, University of Washington, Seattle, WA, USA.; Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA.; Tracy RP; Pathology and Biochemistry, University of Vermont, Burlington, VT, USA.; Alonso A; Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA.; Arking DE; McKusick-Nathans Institute, Department of Genetic Medicine, John Hopkins University School of Medicine, Baltimore, MD, USA.; Coresh J; Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.; Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, MD, USA.; Ballantyne CM; Department of Medicine, Baylor College of Medicine, Houston, TX, USA.; Boerwinkle E; Human Genetics Center, The University of Texas Health Science Center at Houston, Houston, TX, USA.; Grams M; Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.; Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, MD, USA.; Division of Nephrology, Department of Internal Medicine, Johns Hopkins University, Baltimore, MD, USA.; Zhang MZ; Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt O'Brien Center for Kidney Disease, Vanderbilt University Medical Center, Nashville, TN, USA.; Kestenbaum B; Kidney Research Institute, Division of Nephrology, Department of Medicine, University of Washington, Seattle, WA, USA.; Lanktree MB; Department of Medicine and Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada.; St. Joseph's Healthcare Hamilton, Hamilton, Ontario, Canada.; Population Health Research Institute, Hamilton, Ontario, Canada.; Rauh MJ; Department of Pathology and Molecular Medicine, Queen's University, Kingston, Ontario, Canada.; Harris RC Jr; Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt O'Brien Center for Kidney Disease, Vanderbilt University Medical Center, Nashville, TN, USA. ray.harris@vumc.org.; U.S Department of Veterans Affairs, Nashville, TN, USA. ray.harris@vumc.org.; Bick AG; Division of Genetic Medicine, Department of Medicine, School of Medicine, Vanderbilt University, Nashville, TN, USA. alexander.bick@vumc.org.
Source
Publisher: Nature Publishing Company Country of Publication: United States NLM ID: 9502015 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1546-170X (Electronic) Linking ISSN: 10788956 NLM ISO Abbreviation: Nat Med Subsets: MEDLINE
Subject
Language
English
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 V617F -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.
(© 2024. The Author(s).)
(© 2024. The Author(s).)