Kidney Week

Abstract: SA-PO512

Apelin Increases Forearm Blood Flow in CKD

Session Information

• Hypertension and CVD: Clinical - II
  November 04, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Hypertension and CVD

• 1602 Hypertension and CVD: Clinical

Authors

• Chapman, Fiona A., The University of Edinburgh Centre for Cardiovascular Science, Edinburgh, Edinburgh, United Kingdom

Fiona A. Chapman,

• Newby, David E., The University of Edinburgh Centre for Cardiovascular Science, Edinburgh, Edinburgh, United Kingdom

David E. Newby,

• Dhaun, Neeraj, The University of Edinburgh Centre for Cardiovascular Science, Edinburgh, Edinburgh, United Kingdom

Neeraj Dhaun,

Background

Chronic kidney disease (CKD) is a global health emergency. It is independently associated with cardiovascular disease. Despite current treatment patients still progress to kidney failure and/or die from cardiovascular causes. There is an unmet need for newer therapies and apelin, an endothelium-dependent vasodilator and potent inotrope, is an attractive therapeutic target. Clinical studies find apelin improves endothelial function in health and heart failure. We examined the local vascular actions of apelin in CKD.

Methods

Patients with stable, non-diabetic CKD and age- and sex-matched healthy volunteers were recruited to a randomised, placebo-controlled study. Baseline blood pressure and pulse wave velocity were measured. Gold-standard venous occlusion plethysmography was used to examine endothelial function in response to incremental intra-arterial doses of acetylcholine (7.5, 15 and 30μg/min, endothelium-dependent vasodilation), sodium nitroprusside (1, 2 and 4μg/min, endothelium-independent vasodilation), and pyroglutamated apelin-13 ([Pyr¹]apelin-13; 0.3, 1, 3, 10, 30 and 100nmol/min). Circulating tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 assessed endogenous fibrinolysis.

Results

Fifteen patients with CKD (mean age 55±4 years; 53% male) and 15 healthy volunteers (mean age 51±3 years; 67% male) were recruited. In comparison to health, patients with CKD had a higher blood pressure (mean arterial pressure: 102mmHg versus 93mmHg, p<0.05) and increased pulse wave velocity (7.5±2.2 m/s versus 6.0±0.9m/s, p<0.01). Similar dose-dependent vasodilation to acetylcholine and sodium nitroprusside was seen in both groups. [Pyr¹]apelin-13 dose-dependently increased forearm blood flow to a maximum of ~30% in both health and CKD (p<0.01 compared to baseline for both). Net tPA antigen release increased 20-70 fold in both groups, with a trend to a greater release in CKD.

Conclusion

In optimally managed patients with CKD, apelin promotes vasodilation and may regulate fibrinolysis. If maintained longer-term with systemic treatment, apelin would reduce cardiovascular risk. Systemic studies are needed to investigate the haemodynamic and renal effects of apelin in CKD.