Apelin is expressed throughout the human kidney, is elevated in chronic kidney disease & associates independently with decline in kidney function

Abstract

Aims Chronic kidney disease (CKD) is common and cardiovascular disease (CVD) is its commonest complication. The apelin system is a potential therapeutic target for CVD but data relating to apelin in CKD are limited. We examined expression of the apelin system in human kidney, and investigated apelin and Elabela/Toddler (ELA), the endogenous ligands for the apelin receptor, in patients with CKD. Methods Using autoradiography, immunohistochemistry and enzyme‐linked immunosorbent assay, we assessed expression of apelin, ELA and the apelin receptor in healthy human kidney, and measured plasma apelin and ELA in 155 subjects (128 patients with CKD, 27 matched controls) followed up for 5 years. Cardiovascular assessments included blood pressure, arterial stiffness (pulse wave velocity) and brachial artery flow‐mediated dilation. Surrogate markers of endothelial function (plasma asymmetric dimethylarginine and endothelin‐1) and inflammation (C‐reactive protein and interleukin‐6) were measured. Results The apelin system was expressed in healthy human kidney, throughout the nephron. Plasma apelin concentrations were 60% higher in women than men (6.48 [3.62–9.89] vs. 3.95 [2.02–5.85] pg/mL; P < .0001), and increased as glomerular filtration rate declined (R = −0.41, P < .0001), and albuminuria rose (R = 0.52, P < .0001). Plasma apelin and ELA were associated with vascular dysfunction. Plasma apelin associated independently with a 50% decline in glomerular filtration rate at 5 years. Conclusion We show for the first time that the apelin system is expressed in healthy human kidney. Plasma apelin is elevated in CKD and may be a potential biomarker of risk of decline in kidney function. Clinical studies exploring the therapeutic potential of apelin agonism in CKD are warranted.

Expanding the apelin receptor pharmacological toolbox using novel fluorescent ligands

“…This is the first time, to our knowledge, that a fluorescent ligand has been used in this way to explore endogenous apelin receptor in human tissue. The pattern of distribution closely matched previous findings in an immunohistological study assessing apelin expression in the human kidney ( 60 ). One limitation of using 488 nm wavelength fluorophores in tissue section imaging is that there can be considerable interference by autofluorescence of natural proteins such as elastin.…”

WITHDRAWN: Apelin-13 alleviate inflammatory reaction of ischemia reperfusion in rat kidney transplantation via NF-kappa B signaling pathway

“…Apelin receptor mRNAs are found extensively across various tissues, including the brain, lungs, heart, spinal cord, kidneys, adipose tissue, and skeletal muscle [13-15]. In the human kidney, the APJ/apelin system is expressed throughout the renal unit, predominantly in the cortex and vasculature[16, 17]. Activation of the apelin system in the kidney can improve renal blood flow, diuresis, and reduce inflammation and fibrosis[18].…”

Apelin and Copeptin Levels in Patients With Chronic SIAD Treated With Empagliflozin

“…Sex differences in apelin levels remain elusive. One study in healthy volunteers and patients with chronic kidney disease (CKD) found 60% higher plasma apelin concentrations in women than in men [ 15 ], and another study showed that female patients with osteoarthritis had higher apelin levels than men [ 31 ]. In contrast, we did not find a sex difference in SIAD patients, and Blanchard and colleagues also found comparable apelin levels in healthy men and women of more than 60 years of age (age group of our cohort).…”

“…AVP and apelin are secreted from neurosecretory cells of the hypothalamic supraoptic and paraventricular nuclei and apelin receptors [ 12 ] and arginine vasopressin receptors (AVPR)1a/1b are expressed by magnocellular AVP neurons [ 13 ]. In the kidneys, apelin receptors are found in the glomeruli and in all nephron segments including the collecting duct where AVPR2 are also expressed [ 14 , 15 ]. In states of water depletion and hyperosmolality, AVP is released by the posterior pituitary.…”