Clonal hematopoiesis of indeterminate potential and kidney function decline in the general population

Abstract: Rationale and Objective
Clonal hematopoiesis of indeterminate potential (CHIP), defined by the age-related ontogenesis of expanded leukemogenic mutations indicative of a genetically distinct clonal leukocyte population, is associated with risk of hematologic malignancy and cardiovascular disease. In experimental models, recapitulation of CHIP promotes kidney interstitial fibrosis with direct tissue infiltration of donor macrophages. We tested the hypothesis that CHIP is associated with kidney function decline in the general population.
Study Design
Cohort Study: Setting and Participants: 12,004 individuals from three community-based cohorts in the TOPMed Consortium.
Exposure
CHIP status from blood DNA-derived whole genome sequences.
Outcome
Risk of 30% decline in estimated glomerular filtration rate (eGFR) and percent eGFR decline per year during follow-up.
Analytical approach
Cox proportional hazards models for 30% eGFR decline endpoint and generalized estimating equations for annualized relative change in eGFR with meta-analysis. Study-specific estimates were combined using fixed-effect meta-analysis.
Results
Median baseline eGFR was 84 ml/min/1.73m2. Prevalence of CHIP was 6.6%, 9.0% and 12.2% in persons 50-60, 60-70 and >70 years old, respectively. Over a median follow-up of 8 years, 205 kidney function decline events occurred among 1,002 CHIP carriers (2.1 events per 100-person-years), and 2,041 kidney function decline events in persons without CHIP (1.7 events per 100-person-years). In meta-analysis, CHIP was associated with kidney function decline (17% higher risk; 95%CI: 1% to 36% higher; p-value=0.036). Differences were not observed between those with baseline eGFR above or below 60 ml/min/1.73m2, age above or below 60 years, or with or without diabetes.
Limitations
Small number of participants with moderate-to-advanced kidney disease and restricted set of CHIP driver mutations.
Conclusions
We report an association between CHIP and kidney function decline in three general population cohorts without known kidney disease. Further studies are needed to investigate this novel condition and its potential impact among individuals with overt kidney disease

Angaben zum Objekt

• Standort: Deutsche Nationalbibliothek Frankfurt am Main
• Umfang: Online-Ressource
• Sprache: Englisch
• Anmerkungen: American journal of kidney diseases. - 81, 3 (2023) , 329-335, ISSN: 1523-6838

Beteiligte, Orts- und Zeitangaben

• Ereignis: Veröffentlichung
• (wo): Freiburg
• (wer): Universität
• (wann): 2023
• Urheber: Kestenbaum, Bryan ; Bick, Alexander G. ; Vlasschaert, Caitlyn ; Rauh, Michael J. ; Lanktree, Matthew B. ; Franceschini, Nora ; Shoemaker, Moore B. ; Harris, Raymond C. ; Psaty, Bruce M. ; Köttgen, Anna ; Natarajan, Pradeep ; Robinson-Cohen, Cassianne

Weitere Informationen

• DOI: 10.1053/j.ajkd.2022.08.014
• URN: urn:nbn:de:bsz:25-freidok-2302937
• Rechteinformation: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Letzte Aktualisierung: 25.03.2025, 13:42 MEZ