Kidney Week

Abstract: TH-PO0321

Clonal Hematopoiesis of Indeterminate Potential and Premature Cardiovascular Mortality in Patients with ESKD: A Pilot Case-Control Study

Session Information

• Hypertension and CVD: Clinical - 1
  November 06, 2025 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Hypertension and CVD

• 1602 Hypertension and CVD: Clinical

Authors

• Kumari, Usha, The University of Tennessee Health Science Center, Memphis, Tennessee, United States

Usha Kumari, MD

• Han, Zhongji, The University of Tennessee Health Science Center, Memphis, Tennessee, United States

Zhongji Han, PhD

• Mallisetty, Yamini, The University of Tennessee Health Science Center, Memphis, Tennessee, United States

Yamini Mallisetty, MSc, MPH

• Chiu, Chi-Yang, The University of Tennessee Health Science Center, Memphis, Tennessee, United States

Chi-Yang Chiu

• Castro-Bono, Guillem, St Jude Children's Research Hospital, Memphis, Tennessee, United States

Guillem Castro-Bono, MSc

• Kolekar, Pandurang, St Jude Children's Research Hospital, Memphis, Tennessee, United States

Pandurang Kolekar, PhD

• Thota, Swapna, The University of Tennessee Health Science Center, Memphis, Tennessee, United States

Swapna Thota, MD

• Hayes, David Neil, The University of Tennessee Health Science Center, Memphis, Tennessee, United States

David Neil Hayes, MD

• Kovesdy, Csaba P., The University of Tennessee Health Science Center, Memphis, Tennessee, United States

Csaba P. Kovesdy, MD, FASN

• Ma, Xiaotu, St Jude Children's Research Hospital, Memphis, Tennessee, United States

Xiaotu Ma, PhD

• Obeng, Esther, St Jude Children's Research Hospital, Memphis, Tennessee, United States

Esther Obeng, MD, PhD

• Sumida, Keiichi, The University of Tennessee Health Science Center, Memphis, Tennessee, United States

Keiichi Sumida, MD, PhD, MPH, FASN

Background

Clonal hematopoiesis of indeterminate potential (CHIP), an age-related clonal expansion of hematopoietic stem cells driven by somatic mutations, has been causally associated with cardiovascular (CV) morbidity and mortality. However, CHIP prevalence, mutation spectrum, and association with premature CV death in patients with ESKD remain unclear.

Methods

This pilot case-control study comprised 30 hemodialysis (HD) patients who died of a CV event and 30 HD controls who remained alive over the entire follow-up period, matched 1:1 by age, sex, race, and dialysis vintage. We characterized the CHIP mutational profile using a targeted deep sequencing panel of 72 genes and examined the association of CHIP with CV death using multivariable conditional logistic regression with adjustment for potential confounders. A variant allele fraction (VAF) cutoff of ≥0.5% was used to call CHIP.

Results

Patients were 63±12 years old, 60% were male, and median HD vintage was 3.4 years. CHIP mutations were present in 29 of 60 (48.3%) patients, exceeding the reported prevalence in similar-aged non-ESKD populations. The most commonly affected gene was DNMT3A, followed by TET2, PPM1D, and ASXL1. Compared to controls, cases had a higher CHIP prevalence (56.7% vs. 40.0%, P=0.20) and more TET2 and JAK2 mutations, genes strongly associated with CV morbidity in non-ESKD populations (Figure). The presence of CHIP was marginally associated with a higher risk of CV death (adjusted OR [95% CI], 4.01 [0.85-19.0], P=0.080; Table).

Conclusion

CHIP mutations, particularly in DNMT3A and TET2, are prevalent in HD patients and may contribute to their excess risk of premature CV mortality.

Funding

• NIDDK Support

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.202511gk70sx