Kidney Week

Abstract: SA-PO511

Apelin Offers Cardiovascular and Renal Benefits in Health and 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) affects 1 in 10 people and cardiovascular disease is its commonest endpoint. Despite standard-of-care, outcomes remain poor and new therapies are needed. Apelin, an endothelium-dependent vasodilator and inotrope, is a potential novel treatment. We examined the cardiovascular and renal actions of apelin in health and CKD.

Methods

Patients with stable, non-diabetic CKD and age- and sex-matched healthy volunteers were recruited to a randomized, double-blind, placebo-controlled study. Subjects received pyroglutamated apelin-13 ([Pyr¹]apelin-13 (1 nmol/min and 30 nmol/min) or placebo on two study visits. Blood pressure, impedance cardiography and pulse wave velocity were examined. Iohexol and para-aminohippurate clearances determined glomerular filtration rate (GFR) and effective renal blood flow (ERBF), respectively. Tubular function was assessed via urinary electrolyte and free water excretion.

Results

Twelve patients with CKD and 12 healthy volunteers were recruited. Baseline characteristics are shown in Table 1. Compared to placebo, in health and CKD 30 nmol/min [Pyr¹]apelin-13 reduced mean arterial pressure by ~3% and systemic vascular resistance index by ~10-15%, and increased cardiac index by ~10-15% (p<0.05 for all comparisons).

In health and CKD, 1 nmol/min and 30 nmol/min [Pyr¹]apelin-13 had similar effects on renal endpoints. ERBF increased by ~15% (p<0.01 compared to placebo in both groups). In CKD only, GFR fell by ~4 mL/min, filtration fraction by ~3% and proteinuria by ~25% (p<0.01 compared to placebo for all). [Pyr¹]apelin-13 promoted natriuresis and free water clearance in health and CKD. Overall, the effects of apelin were prolonged in CKD.

Conclusion

Apelin has cardiovascular and renal benefits in CKD. If maintained long-term these would improve cardiovascular and renal outcomes. Clinical trials of long-acting oral apelin analogues are justified in CKD and other conditions with impaired salt and water balance.

Baseline characteristics