Kidney Week

Abstract: SA-PO335

Evaluation of Plasma Proteins as Mediators of the Relationship between Kidney Disease and Heart Failure

Session Information

• Hypertension, CVD, and the Kidneys: Clinical Research
  October 26, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Hypertension and CVD

• 1602 Hypertension and CVD: Clinical

Authors

• Lidgard, Benjamin, University of Washington, Seattle, Washington, United States

Benjamin Lidgard, MD

• Limonte, Christine P., University of Washington, Seattle, Washington, United States

Christine P. Limonte, MD

• Kizer, Jorge R., University of California San Francisco School of Medicine, San Francisco, California, United States

Jorge R. Kizer, MD, MSc

• Psaty, Bruce M., University of Washington, Seattle, Washington, United States

Bruce M. Psaty, MD, PhD

• Zelnick, Leila R., University of Washington, Seattle, Washington, United States

Leila R. Zelnick, PhD

• Bansal, Nisha, University of Washington, Seattle, Washington, United States

Nisha Bansal, MD, FASN

• Brody, Jennifer A., University of Washington, Seattle, Washington, United States

Jennifer A. Brody

Background

Patients with chronic kidney disease (CKD) are at high risk for heart failure (HF). Plasma proteins may indicate pathways associated with both reduced estimated glomerular filtration rate (eGFR) and HF. We tested if circulating proteins may mediate the associations between eGFR and HF.

Methods

We used the SomaLogic 5K platform to measure plasma proteins in 2,993 participants without prevalent HF in the Cardiovascular Health Study. We used linear regression to evaluate associations of each protein with eGFR (by the 2021 combined CKD-Epi equation), and proportional hazards models for associations with HF events. We used a quasi-Bayesian Monte Carlo method with 2,000 draws to test the adjusted mediation effects of proteins (which were associated with both eGFR and HF) on the eGFR-HF association. Bonferroni corrections were used for significance.

Results

The mean (SD) eGFR was 70 (16) mL/min/1.73 m²; mean age was 74 (5) years. 1074 proteins were significant associated with eGFR. Of these, 44 proteins were significantly associated with incident HF; each was associated with statistically significant mediation effect on the association between eGFR and HF. These included COSA1 (proportion mediated 62%, 95% CI 39-93%) and NT-proBNP (proportion mediated 33%, 95% CI 24-47%).

Conclusion

Multiple plasma proteins were associated with significant mediation effect on association between eGFR and HF. These proteins may indicate pathways by which CKD increases HF risk. However, these statistical mediation analyses assume the directionality of associations. Ongoing work is investigating directionality of associations and joint mediation analyses.

Funding

• Other NIH Support