Abstract: SA-PO1167
Biomarkers Associated with Albuminuria in Heart Failure with Preserved Ejection Fraction (HFpEF)
Session Information
- CKD: SGLT2 Inhibitors and GLP-1 RAs for Kidney Health
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2302 CKD (Non-Dialysis): Clinical, Outcomes, and Trials
Authors
- Roehm, Bethany Angela, The University of Texas Southwestern Medical Center, Dallas, Texas, United States
- Zhang, Xiaoyue, Stony Brook University, Stony Brook, New York, United States
- Yang, Jie, Stony Brook University, Stony Brook, New York, United States
- Grodin, Justin, The University of Texas Southwestern Medical Center, Dallas, Texas, United States
- Wang, Thomas J., The University of Texas Southwestern Medical Center, Dallas, Texas, United States
- Hedayati, Susan, Stony Brook University, Stony Brook, New York, United States
Background
Albuminuria is associated with greater LV mass and greater risk of heart failure hospitalization and mortality in people with HFpEF. We investigated whether easily-measured baseline circulating proteins predicted a differential increase in albuminuria at 12 months of randomly assigned treatment with spironolactone vs. placebo in 75 people with HFpEF from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial.
Methods
Linear regression was used to determine if baseline levels of each of 92 candidate proteins at baseline, using Olink proteomics, was associated with change in ACR from baseline to month 12. Logistic regression investigated the association of the proteins with any increase in ACR at 12 months. Models were adjusted for age, sex, diabetes, NYHA class, BMI, and interaction of protein X treatment.
Results
ACR increased from 93 (SD) (190) to 260 (645) in 18 (56%) participants in the placebo vs. from 42 (52) to 167 (260) in 15 (35%) in the spironolactone arm, p=0.065. 23 proteins were associated with change in ACR or exhibited differing associations between treatments arms (p=<0.0001-0.04). Higher levels of 5 proteins (TFF3, CCL16, LTBR, EPHB4, PLC) were associated with a higher increase in ACR, while treatment with spironolactone attenuated this association so that there was a lower increase in ACR, interaction p=0.003-0.04 (Figure 1A). Furthermore, higher baseline levels of CCL16, EPHB4, and LTBR were associated with higher risk of increase in proteinuria in the placebo but not the spironolactone arm (Figure 1B).
Conclusion
These biomarkers, proposed to be involved in endothelial dysfunction, podocyte apoptosis, or tubular injury, deserve further investigation to see if they can aid in early identification of at-risk people with HFpEF by adding information about ACR progression and whether they can be used to predict who will respond to treatments that antagonize aldosterone.
Funding
- Other NIH Support