Kidney Week

Abstract: FR-PO250

Clonal Hematopoiesis of Indeterminate Potential Is Associated with Kidney Disease Progression in a Multi-Cohort Meta-Analysis of Individuals with CKD

Session Information

• Onconephrology: From AKI to CKD and Everything in Between
  November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Onconephrology

• 1700 Onconephrology

Authors

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

Caitlyn Vlasschaert,

• Pan, Yang, University of Illinois System, Urbana, Illinois, United States

Yang Pan,

• Rao, Varun S., University of Illinois System, Urbana, Illinois, United States

Varun S. Rao,

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

James E. Hixson,

• Chong, Michael R., McMaster University, Hamilton, Ontario, Canada

Michael R. Chong,

• Akwo, Elvis Abang, Vanderbilt University Medical Center, Nashville, Tennessee, United States

Elvis Abang Akwo,

• Uddin, Md Mesbah, Harvard Medical School, Boston, Massachusetts, United States

Md Mesbah Uddin,

• Yu, Zhi, Harvard Medical School, Boston, Massachusetts, United States

Zhi Yu,

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

Do-Kyun Kim,

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

Manjula Tamura,

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

Debbie L. Cohen,

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

Jiang He,

• Li, Changwei, Tulane University, New Orleans, Louisiana, United States

Changwei Li,

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

Zeenat Yousuf Bhat,

• Rao, Panduranga S., University of Michigan, Ann Arbor, Michigan, United States

Panduranga S. Rao,

• 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,

• Pare, Guillaume, McMaster University, Hamilton, Ontario, Canada

Guillaume Pare,

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

Michael J. Rauh,

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

Adeera Levin,

• Natarajan, Pradeep, Harvard Medical School, Boston, Massachusetts, United States

Pradeep Natarajan,

• Lash, James P., University of Illinois System, Urbana, Illinois, United States

James P. Lash,

• 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,

• Kelly, Tanika, University of Illinois System, Urbana, Illinois, United States

Tanika Kelly,

Background

Clonal hematopoiesis of indeterminate potential (CHIP) is a common inflammatory condition of aging caused by acquired mutations in blood stem cells. CHIP causes myriad end-organ damage, including a doubling of the risk of cardiovascular disease independent of traditional risk factors. We have recently shown associations for CHIP with acute kidney injury and with kidney function decline in the general population, with a greater effect for CHIP driven by mutations in genes other than DNMT3A (non-DNMT3A CHIP). Longitudinal kidney function endpoints in individuals with pre-existing chronic kidney disease (CKD) and CHIP have been examined in two previous studies, which reported conflicting findings and were limited by small sample sizes.

Methods

In this study, we examine the prospective associations between CHIP and CKD progression events in four cohorts of CKD patients: the Chronic Renal Insufficiency Cohort (CRIC), the African American Study of Kidney Disease (AASK), the Canadian study of prediction of death, dialysis and interim cardiovascular events (CanPREDDICT), and BioVU (total N = 4853). The primary outcome was CKD progression (composite of 50% kidney function decline or end-stage kidney disease). Analyses were adjusted for age, age², sex, self-reported race, and the following baseline parameters: eGFR, proteinuria, smoking status, BMI, diabetes status, hypertension, and cardiovascular disease history.

Results

Across all cohorts, the average age was 67.4 years, the average baseline eGFR was 41.2 ml/min/1.73m², and 25% had CHIP. In a random-effects meta-analysis, non-DNMT3A CHIP was associated with a 59% increased risk of incident CKD progression (HR 1.59, 95% CI: 1.01-2.51). This effect was slightly more pronounced in the subgroup with baseline eGFR ≥ 30 ml/min/1.73m² (HR 1.77, 95% CI: 1.06-2.98).

Conclusion

Non-DNMT3A CHIP is a potentially targetable novel risk factor for CKD progression in a multi-cohort meta-analysis.

Funding

• NIDDK Support