#1322 VEGF therapy improves cardio-renal pathophysiology in a novel model of CKD-HFpEF

Abstract Background and Aims Patients with chronic kidney disease (CKD) have a higher risk of developing heart failure with preserved ejection fraction (HFpEF). We developed a model of CKD-HFpEF and showed that renal-cardio pathophysiology is associated with decreased expression and availability of vascular endothelial growth factor in both organs. We showed that renal VEGF therapy improved renal function in our model. We hypothesize that cardiac VEGF therapy will improve cardiac function and will investigate whether cardiac protection in CKD also carries recovery of renal function. Method CKD and normal pigs (n = 4 each, 2 males/2 females) were studied for 14 weeks. In addition, CKD-HFpEF (n = 4, 2 males/2 females) were treated after 6 weeks of disease with a single intracoronary (IC) administration of VEGF attached to a drug-delivery vector (ELP-VEGF) that increases cardiac targeting, and effects quantified 8 weeks later. Renal (multi-detector CT) and cardiac (echocardiography, PV loops) morphology and function were quantified in vivo, microvascular (MV) density (3D micro-CT) ex vivo, and cardiac expression of VEGF was quantified by qPCR. Results Cardiac function, VEGF expression, and MV density were improved after IC ELP-VEGF therapy compared to placebo. Notably, renal hemodynamics (expressed as % change) were significantly improved compared to pre-treatment values and to time-matched untreated CKD-HFpEF pigs (Figure). Conclusion Our study suggests strong crosstalk between the heart and the kidney in a pre-clinical model of CKD-HFpEF. Renal and cardiac hemodynamics were significantly improved after cardiac VEGF therapy, conceptually supporting a cardio-renal axis in CKD and showing the extent of beneficial effects of a novel targeted intervention in a translational fashion.