Kidney Week

Abstract: SA-PO1097

Association of Transthyretin Val122Ile Variant with Kidney Outcomes in Black Participants of REGARDS

Session Information

• CKD: Epidemiology, Risk Factors, and Prevention - 3
  October 26, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2301 CKD (Non-Dialysis): Epidemiology, Risk Factors, and Prevention

Authors

• Khanna, Soumya, The University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama, United States

Soumya Khanna, MPH

• Cheung, Katharine L., University of Vermont The Robert Larner MD College of Medicine, Burlington, Vermont, United States

Katharine L. Cheung, MD, MS, PhD, FASN

• Cushman, Mary, University of Vermont The Robert Larner MD College of Medicine, Burlington, Vermont, United States

Mary Cushman

• Ilori, Titilayo O., Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts, United States

Titilayo O. Ilori, MD, MS, MSc

• Irvin, Marguerite, The University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama, United States

Marguerite Irvin, PhD

• Gutierrez, Orlando M., The University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama, United States

Orlando M. Gutierrez, MD

Background

A TTR gene variant (Val122Ile) causes misfolded tetrameric transthyretin protein, accumulating as extracellular amyloid fibrils and causing the most common form of hereditary transthyretin amyloidosis in Black Americans associated with incident heart failure. Whether this variant impacts kidney function through amyloid protein deposition is unclear.

Methods

In 8669 Black participants of the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study with complete data on TTR genotyping and kidney function measures, we examined the association of the TTR Val122Ile (rs76992529) genotype with (1) estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (ACR) at the baseline visit and (2) risk of incident end-stage kidney disease (ESKD). We used linear regression and Cox proportional hazards models adjusted for genetic ancestry and socio-demographic and clinical factors.

Results

A total of 265 participants carried the TTR Val122Ile variant while 8404 participants were non-carriers. There were no significant differences in baseline characteristics between the two groups, including baseline eGFR and ACR (Table). In linear regression adjusted for genetic ancestry, sociodemographic and clinical factors, there were no significant associations of TTR Val122Ile carriage with eGFR (1.22±1.48; p=0.41) or ACR (-0.007±.09; p=0.43). After a mean 8±3 years of follow-up, 400 participants developed ESKD. There was no significant association of TTR Val122Ile carriage with incident ESKD in fully adjusted analyses (hazard ratio 0.59, 95%CI 0.25,1.44).

Conclusion

Despite an association with left ventricular hypertrophy and heart failure via extracellular amyloid fibril deposition, the TTR Val122Ile variant was not associated with kidney function or development of ESKD in a community-based sample of Black Americans.

Funding

• Other NIH Support