Abstract 17326: Urine Exosomes Proteomics for Parenchymal Kidney Health in Heart Failure Patients With Mechanical Circulatory Support

Abstract

Introduction: Kidney dysfunction frequently affects heart failure (HF) patients with left ventricular assist device (LVAD) support and is linked to unfavorable outcomes. However, the effects of LVAD support on parenchymal kidney health are uncertain. We performed a pilot study on urine exosome proteomics in LVAD recipients as they offer a non-invasive glimpse into kidney cellular states. Methods: We collected urine samples from 33 patients who underwent LVAD (HeartMate III) surgery between 01/2022-02/2023. Urine exosomes were isolated from the samples collected before the operation and on the 7th day after surgery. The exosome fraction underwent untargeted proteomics using LC-MS/MS and iBAQ quantification. Our investigation focused on identifying and studying kidney-enhanced proteins. Results: The exosomes isolated were verified by canonical exosome proteins (CD63, Hsp70) and TEM imaging (Fig.A,B), with 82.7% of exosomes between 51-120 nm (Fig.C). Over 7K strict genes were identified with an average of 1,150 proteins (Fig.D,E). In GO analysis, exosomes were the primary cellular compartment represented (Fig.F). A total of 176 kidney-enhanced proteins were present in >50% of samples. Differential expression analysis revealed 8 proteins with increased expression on the 7 th day after surgery with FDR<0.1(Fig.G). The 2 top proteins were glutathione peroxidase 3 (GPX3, log2 FC 3.4 [95%CI 2.1-4.8]), and fatty acid binding protein 3 (FABP3, log2 FC 2.9 [95%CI 1.7-4.2]). Enrichment analysis (Fig.H) demonstrated pathway changes consistent with inflammatory and ischemic kidney damage, metabolic dysfunction, and fibrotic transformation, consistent with kidney stress from advanced HF and cardiac surgery. Conclusions: We have demonstrated the feasibility of urine exosomes for non-invasive parenchymal kidney health assessment in LVAD patients. Further investigation in a larger cohort with additional sampling points may be warranted.