#3840 THE SYSTEMIC AND RENAL HAEMODYNAMIC EFFECTS OF APELIN IN HEALTH AND CHRONIC KIDNEY DISEASE

Abstract Background and Aims Chronic kidney disease (CKD) is a leading cause of global morbidity mortality independently associated with cardiovascular disease. Indeed, patients CKD are more likely to die than they progress failure. Despite current standard care, outcomes remain poor newer therapies needed. Apelin, an endothelium-dependent vasodilator potent inotrope, potential novel treatment for CKD. There no clinical studies the renal actions apelin, but pre-clinical data show that it regulates glomerular haemodynamics promotes aquaresis. We investigated apelin in healthy volunteers Method Patients stable, non-diabetic age- sex-matched were recruited prospective, randomised, double-blind placebo-controlled study. Subjects received either pyroglutamated apelin-13 ([Pyr1]apelin-13, 1 nmol/min 30 nmol/min) or placebo on two separate visits. Cardiovascular assessments included blood pressure, impedance cardiography pulse wave velocity; iohexol para-aminohippurate clearance used assess filtration rate (GFR) flow, respectively. Tubular function was examined via urinary sodium, potassium free water excretion. Results Twelve 12 completed both phases study protocol. Baseline characteristics shown Table 1. Whilst infusion [Pyr1]apelin-13 did not affect systemic haemodynamics, led significant changes. Compared placebo, mean arterial pressure fell by 3 mmHg 4 health CKD, respectively (p<0.05 groups), vascular resistance index 309 dynes*s*cm−5 m2 407 m2, (p<0.01 groups). Cardiac increased 0.3 L/min/m2 0.2 L/min/m2, groups compared placebo). In contrast, had similar effects haemodynamics. Effective flow ∼15% GFR ∼4 mL/min (p<0.01) we observed change volunteers. As result these changes effective GFR, fraction ∼3% reflected fall proteinuria ∼25% (p<0.001 both). Both low high doses promoted natriuresis comparison sodium excretion ∼30% all comparisons). Overall, prolonged Conclusion Apelin offers haemodynamic benefits If maintained longer-term would translate improved this at-risk patient group. Clinical trials long-acting, oral analogues now justified other conditions impaired salt balance.