Abstract 10273: Proteomic Analysis of Chronic Kidney Disease (CKD) in Heart Failure With Preserved Ejection Fraction (HFpEF)

Abstract

Introduction: CKD is highly prevalent in HFpEF and is associated with increased morbidity and mortality. The biologic correlates of CKD in HFpEF are not well understood. We conducted a plasma proteomics analysis to assess biologic pathways associated with CKD in HFpEF. Methods: We utilized biosamples from TOPCAT for de novo measurements of 4776 plasma proteins using the SomaScan (version 4) proteomic assay, among 218 participants enrolled in the Americas. Linear regression and pathway analyses were used to study the relationship of proteins and pathways to the estimated glomerular filtration rate (eGFR). All regression estimates are standardized (per unit increase in z score) to facilitate comparisons. Results: After correction for multiple comparisons, we identified 73 proteins associated with eGFR. The strongest positively associated proteins were contactin-4, contactin-1, laminin-2, tenascin-X, and neuropilin-2. Proteins with the strongest negative association were transmembrane emp24 domain-containing protein 10, desmocollin-2, beta-2-microglobulin, neutrophil gelatinase-associated lipocalin, and cystatin C ( Figure 1 ). Biologic pathways associated with eGFR included complement system, acute phase response signaling, apoptosis, lysosomal expression and regulation, inflammation, fibrosis, chondroitin and dermatan sulfate degradation, notch signaling, and gluconeogenesis ( Figure 2 ). Conclusions: Using a broad proteomics approach, we identified novel biomarkers and pathways associated with renal dysfunction in HFpEF. Further research is required to assess whether targeting these pathways can ameliorate renal dysfunction in HFpEF patients.