Kidney Week

Abstract: FR-OR95

Associations Between Clonal Hematopoiesis of Indeterminate Potential and Cardiovascular Disease in Three Prospective CKD Patient Cohorts

Session Information

• Novel Clinical Impacts on Cardiorenal Disease
  November 03, 2023 | Location: Room 103, Pennsylvania Convention Center
  Abstract Time: 05:06 PM - 05:15 PM

Category: Hypertension and CVD

• 1602 Hypertension and CVD: Clinical

Authors

• Pan, Yang, University of Illinois Chicago, Chicago, Illinois, United States

Yang Pan, MS, PhD

• Vlasschaert, Caitlyn, Queen's University, Kingston, Ontario, Canada

Caitlyn Vlasschaert,

• Rao, Varun S., University of Illinois Chicago, Chicago, Illinois, United States

Varun S. Rao,

• Hixson, James E., The University of Texas Health Science Center at Houston, Houston, Texas, United States

James E. Hixson,

• Uddin, Md Mesbah, Broad Institute, Cambridge, Massachusetts, United States

Md Mesbah Uddin,

• Yu, Zhi, Broad Institute, Cambridge, Massachusetts, United States

Zhi Yu,

• Kim, Do-Kyun, The University of Texas Health Science Center at Houston, Houston, Texas, United States

Do-Kyun Kim,

• Bick, Alexander, Vanderbilt University Medical Center, Nashville, Tennessee, United States

Alexander Bick,

• Kestenbaum, Bryan R., University of Washington, Seattle, Washington, United States

Bryan R. Kestenbaum,

• Rauh, Michael J., Queen's University, Kingston, Ontario, Canada

Michael J. Rauh,

• Levin, Adeera, The University of British Columbia Faculty of Medicine, Vancouver, British Columbia, Canada

Adeera Levin,

• Lash, James P., University of Illinois Chicago, Chicago, Illinois, United States

James P. Lash,

• Tamura, Manjula, Stanford University, Stanford, California, United States

Manjula Tamura,

• Cohen, Debbie L., University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States

Debbie L. Cohen,

• He, Jiang, Tulane University, New Orleans, Louisiana, United States

Jiang He,

• Hamm, L. Lee, Tulane University, New Orleans, Louisiana, United States

L. Lee Hamm,

• Deo, Rajat, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States

Rajat Deo,

• Bhat, Zeenat Yousuf, University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States

Zeenat Yousuf Bhat,

• Rao, Panduranga S., University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States

Panduranga S. Rao,

• Natarajan, Pradeep, Broad Institute, Cambridge, Massachusetts, United States

Pradeep Natarajan,

• Kelly, Tanika, University of Illinois Chicago, Chicago, Illinois, United States

Tanika Kelly,

• Robinson-Cohen, Cassianne, Vanderbilt University Medical Center, Nashville, Tennessee, United States

Cassianne Robinson-Cohen,

• Lanktree, Matthew B., McMaster University, Hamilton, Ontario, Canada

Matthew B. Lanktree,

Background

Clonal hematopoiesis of indeterminate potential (CHIP) is an age-related condition characterized by the clonal expansion of blood cells carrying somatic mutations to specific driver genes. Although CHIP has been established as an important contributor to cardiovascular diseases (CVD) in the general population, its association with CVD in a pro-inflammatory chronic kidney disease (CKD) setting has not been examined.

Methods

We examined prospective associations between CHIP status and CVD events in three cohorts that included a total of 3,414 CKD patients: the Chronic Renal Insufficiency Cohort (CRIC), the African American Study of Kidney Disease (AASK), and the Canadian study of prediction of death, dialysis and interim cardiovascular events (CanPREDDICT). Primary analyses tested associations between CHIP status and a composite CVD endpoint of myocardial infarction (MI), stroke, congestive heart failure (CHF), or peripheral artery disease (PAD). Cox proportional hazards regression models were used, adjusting for demographic, lifestyle, and clinical covariables, including cardiovascular risk factors. Secondary analyses investigated individual CVD endpoints. Random-effect meta-analyses were employed to combine effects across studies.

Results

Study participants had an average age of 68.8 years and a mean eGFR of 40.2 ml/min/1.73m². As expected, participants had a high frequency of hypertension (95%) and diabetes (49%), with CHIP identified in 25% of participants. Those with large CHIP clone size (VAF≥10%) and a non-DNMT3A CHIP gene mutation exhibited 38% (95% CI:2%-85%) and 42% (95% CI: 6%-90%) higher risks of the composite CVD endpoint, respectively, compared to noncarriers. Compared to non-CHIP status, large clone size was further associated with incident CHF (HR: 1.53, 95% CI: 1.13-2.00).

Conclusion

CHIP carrier status may be an important risk factor for CVD among CKD patients, with associations mirroring those observed in the general population.

Funding

• NIDDK Support