Abstract: FR-PO093
Clonal Hematopoiesis of Indeterminate Potential Is Associated with AKI
Session Information
- AKI: Epidemiology, Risk Factors, Prevention - I
November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 101 AKI: Epidemiology, Risk Factors, and Prevention
Authors
- Vlasschaert, Caitlyn, Queen's University, Kingston, Ontario, Canada
- Kestenbaum, Bryan R., University of Washington, Seattle, Washington, United States
- Silver, Samuel A., Queen's University, Kingston, Ontario, Canada
- Chen, Jianchun, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Akwo, Elvis Abang, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Bhatraju, Pavan K., University of Washington, Seattle, Washington, United States
- Zhang, Ming-Zhi, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Cao, Shirong, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Jiang, Ming, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Niu, Aolei, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Siew, Edward D., Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Kramer, Holly J., Loyola University Chicago, Chicago, Illinois, United States
- Kottgen, Anna, Albert-Ludwigs-Universitat Freiburg Universitatsklinikum Freiburg, Freiburg, Baden-Württemberg, Germany
- Franceschini, Nora, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
- Psaty, Bruce M., University of Washington, Seattle, Washington, United States
- Alonso, Alvaro, Emory University, Atlanta, Georgia, United States
- Arking, Dan, Johns Hopkins University, Baltimore, Maryland, United States
- Coresh, Josef, Johns Hopkins University, Baltimore, Maryland, United States
- Ballantyne, Christie, Baylor College of Medicine, Houston, Texas, United States
- Grams, Morgan, Queen's University, Kingston, Ontario, Canada
- Lanktree, Matthew B., McMaster University, Hamilton, Ontario, Canada
- Rauh, Michael J., Queen's University, Kingston, Ontario, Canada
- Bick, Alexander, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Harris, Raymond C., Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Robinson-Cohen, Cassianne, Vanderbilt University Medical Center, Nashville, Tennessee, United States
Background
Clonal hematopoiesis of indeterminate potential (CHIP) is a recently recognized risk factor for several chronic diseases of aging including cardiovascular disease and chronic kidney disease. In these contexts, clonal populations of mutated myeloid cells contribute to end-organ damage through inflammatory dysregulation. We recently identified CHIP as a novel risk factor for AKI: it was associated with an increased risk of incident AKI in ICD code-based prospective clinical data from three large cohorts totalling nearly half a million individuals (adjusted hazard ratio: 1.26, 95% CI: 1.19–1.34).
Methods
In the current work, we sought to investigate determine whether CHIP was associated with impaired functional recovery from AKI. We first examined the association between CHIP and AKI recovery in the ASSESS-AKI cohort. We then assessed long-term post-AKI outcomes in a mouse model of CHIP (partial Tet2-/- bone marrow transplant) subjected to ischemia reperfusion injury.
Results
We identified that certain subtypes of CHIP exhibited a non-resolving pattern of injury and had poorer long-term outcomes after AKI. At 28 days post-ischemic injury, we observed higher levels of kidney injury markers KIM-1 and NGAL as well as more kidney fibrosis in the CHIP mice compared to wild type mice. Kidney macrophage infiltration was markedly increased in CHIP mice at this timepoint, and concomitant upregulation of pro-inflammatory and fibrotic signaling pathways was noted.
Conclusion
This work identifies CHIP as a novel and potentially targetable risk factor for impaired recovery from AKI.
Funding
- NIDDK Support