#4063 APELIN INCREASES FOREARM BLOOD FLOW IN CHRONIC KIDNEY DISEASE

Abstract Background and Aims Chronic kidney disease (CKD) affects 1 in 10 people cardiovascular is its commonest complication. Despite current standard of care, many patients continue to progress failure and/or die disease. Thus, there an urgent unmet need for new treatments that slow function decline offer broad protection. The apelin system, comprising the receptor two endogenous ligands elabela, attractive therapeutic target CKD. Apelin endothelium-dependent vasodilator a potent inotrope. Clinical studies show improves endothelial health heart failure, pre-clinical models find offers renoprotection. At present, has not been studied with aims this study were examine local vascular actions Method Participants stable, non-diabetic CKD age- sex-matched healthy volunteers recruited prospective, randomised, placebo-controlled study. Blood pressure arterial stiffness (measured using pulse wave velocity) assessed at baseline. Endothelial was examined gold-standard venous occlusion plethysmography. Forearm vasodilatation measured response incremental intra-arterial doses acetylcholine (7.5, 15 30 μg/min, used assess vasodilatation), sodium nitroprusside (1, 2 4 endothelium-independent pyroglutamated apelin-13 ([Pyr1]apelin-13; 0.3, 1, 3, 10, 100 nmol/min). Circulating tissue plasminogen activator (tPA) inhibitor-1 (PAI-1) as measures fibrinolysis. Results Fifteen (mean age 55±4 years; 53% male) 51±3 67% completed In comparison volunteers, had higher blood pressure: 102 mmHg versus 93 mmHg, p<0.05) increased velocity (7.5±2.2 m/s 6.0±0.9 m/s, p<0.01). Similar dose-dependent seen both groups. [Pyr1]apelin-13 forearm flow by maximum ∼30% (p<0.01 compared baseline both) (Figure 1). This appeared be dose-dependent. Net tPA antigen release 20-70 fold CKD, trend greater There no change PAI-1. No relationship between function. Conclusion promotes optimally managed may regulate If effect maintained long-term systemic treatment, it would expected reduce risk. Systemic are now justified investigate haemodynamic renal effects these patients.