Abstract: FR-PO0531
Association of Peptidase Inhibitor 3 (PI3) with Kidney Outcomes in Heart Failure with Preserved Ejection Fraction (HFpEF) and Attenuation by Spironolactone
Session Information
- CKM: Clinical - Trials, Epidemiology, and Biomarkers
October 23, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Cardiovascular-Kidney-Metabolic Health
- 602 Cardiovascular-Kidney-Metabolic Health: Clinical
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
- Hedayati, Susan, Stony Brook University, Stony Brook, New York, United States
Background
Decline in GFR and increase in UACR are common in people with HFpEF. Aldosterone receptor blockers ameliorate proteinuria but may cause a decrease in GFR in some individuals. It is imperative to risk-stratify individuals with HFpEF at higher risk for adverse kidney events and whether treatment with aldosterone receptor blockers may attenuate risk. We aimed to identify candidate biomarkers associated with GFR decline and UACR increase in participants of TOPCAT, a randomized trial of spironolactone vs. placebo in HFpEF, and whether spironolactone modifies these associations.
Methods
We included 69 patients from the U.S. and Canada with both serum and UACR available at baseline and 12 mo. Using Olink proteomics, we analyzed 92 candidate proteins in serum samples stored in BIOLINCC. Linear regression and linear mixed effect models tested the association of proteins and longitudinal change in protein with changes in GFR and UACR at 12 mo stratified by treatment group, respectively. Models were adjusted for age, sex, diabetes, NYHA class, and BMI.
Results
Baseline levels of 6 proteins were associated with an increase in GFR over 12 mo (Fig 1A). Three proteins were associated with a decrease and 16 with an increase in UACR over 12 mo (Fig 1A). Only PI3 exhibited consistent associations with both GFR and UACR. Higher baseline PI3 was associated with increase in GFR at 12 mo in the spironolactone (β 5.9, p=0.007) but not placebo group. Increase in PI3 from baseline to 12 mo was associated with decrease in GFR in both groups (Fig 1B). An increase in UACR at 12 mo was associated with higher baseline PI3 (β 249, p=0.0001) and increase in PI3 (β 115, p=0.03) in the placebo but not in the spironolactone group.
Conclusion
Future studies should explore the role of serum PI3 as a potential biomarker to risk stratify kidney outcomes in people with HFpEF treated with aldosterone receptor blockers.
Funding
- Other NIH Support