Nature Reviews. Nephrology | 2021
The therapeutic potential of apelin in kidney disease
Abstract
Chronic kidney disease (CKD) is a leading cause of global morbidity and mortality and is independently associated with cardiovascular disease. The mainstay of treatment for CKD is blockade of the renin–angiotensin–aldosterone system (RAAS), which reduces blood pressure and proteinuria and slows kidney function decline. Despite this treatment, many patients progress to kidney failure, which requires dialysis or kidney transplantation, and/or die as a result of cardiovascular disease. The apelin system is an endogenous physiological regulator that is emerging as a potential therapeutic target for many diseases. This system comprises the apelin receptor and its two families of endogenous ligands, apelin and elabela/toddler. Preclinical and clinical studies show that apelin receptor ligands are endothelium-dependent vasodilators and potent inotropes, and the apelin system has a reciprocal relationship with the RAAS. In preclinical studies, apelin regulates glomerular haemodynamics and acts on the tubule to promote aquaresis. In addition, apelin is protective in several kidney injury models. Although the apelin system has not yet been studied in patients with CKD, the available data suggest that apelin is a promising potential therapeutic target for kidney disease. The apelin system is a broad regulator of physiology that has beneficial cardiovascular and renal effects. This Review focuses on the role of this system in kidney and cardiovascular health and disease and its potential as a therapeutic target. Chronic kidney disease (CKD) is common worldwide and is associated with high cardiovascular morbidity and mortality; however, treatment options are limited. The apelin system is a broad regulator of physiology that opposes the renin–angiotensin–aldosterone system (RAAS) and has beneficial cardiovascular effects in health and disease. Increasing evidence indicates that apelin has favourable effects on renal physiology, including roles in the regulation of fluid balance and glomerular haemodynamics. Preclinical models demonstrate direct anti-inflammatory and anti-fibrotic actions of the apelin system in models of kidney injury; targeting the apelin receptor in combination with RAAS blockers might offer synergistic benefits. The apelin system is an attractive potential therapeutic target for CKD, offering direct renal protection in addition to targeting the associated cardiovascular complications. Chronic kidney disease (CKD) is common worldwide and is associated with high cardiovascular morbidity and mortality; however, treatment options are limited. The apelin system is a broad regulator of physiology that opposes the renin–angiotensin–aldosterone system (RAAS) and has beneficial cardiovascular effects in health and disease. Increasing evidence indicates that apelin has favourable effects on renal physiology, including roles in the regulation of fluid balance and glomerular haemodynamics. Preclinical models demonstrate direct anti-inflammatory and anti-fibrotic actions of the apelin system in models of kidney injury; targeting the apelin receptor in combination with RAAS blockers might offer synergistic benefits. The apelin system is an attractive potential therapeutic target for CKD, offering direct renal protection in addition to targeting the associated cardiovascular complications.