Pathophysiology of copeptin in kidney disease and hypertension

Abstract

Copeptin is derived from the cleavage of the precursor of arginine vasopressin (AVP), produced in an equimolar ratio in hypothalamus and processed during axonal transport AVP is an unstable peptide and has a short half-life of 5–20 min. Unlike AVP, copeptin is a stable molecule and can easily be measured. Recent evidence suggest that increased copeptin levels have been associated with worse outcomes in various clinical conditions including chronic kidney disease (CKD) and hypertension. In this review, the data regarding copeptin with kidney function (evaluated as glomerular filtration rate, increased albumin/protein excretion or both) and hypertension with regard to performed studies, prognosis and pathogenesis was summarised.

Salt, water and nephron: Mechanisms of action and link to hypertension and chronic kidney disease

“…Chronic high‐salt intake, on the contrary, activates an aberrant pathway involving BDNF/Trk activation, which leads to KCC2 channel inhibition; the latter collapses the transmembrane Cl − gradient, causing the AVP‐producing MCN to erroneously respond to the inhibitory GABAergic signal as an AVP stimulatory signal . In essence, sustained high‐salt intake turns the negative feedback loop into a positive one, resulting in an exaggerated AVP production and vasoconstriction . A superimposed under‐hydration (signified by a high‐normal serum Na + concentration) would further augment AVP secretion.…”

“…34,35 In essence, sustained high-salt intake turns the negative feedback loop into a positive one, resulting in an exaggerated AVP production and vasoconstriction. 36,37 A superimposed under-hydration (signified by a high-normal serum Na + concentration) would further augment AVP secretion. Moreover, high-salt intake has been shown to elevate endothelin-1 (ET-1) which participates in the regulation of the skin storage pool of Na + , influencing blood pressure and diurnal pressure rhythm.…”

Relationship between water and salt intake, osmolality, vasopressin, and aldosterone in the regulation of blood pressure

“…Serum copeptin is derived from the cleavage of the precursor of arginine vasopressin, and it is used as a surrogate marker of vasopressin, since it correlates with plasma levels of vasopressin and it is a stable molecule and easy to measure. Several studies have evidenced increased levels of copeptin in different pathological conditions, such as metabolic syndrome, chronic kidney disease, and hypertension . In particular, copeptin levels have been associated with office BP and ambulatory BP, resistant hypertension, and essential hypertension in adolescents, suggesting a certain role in arterial hypertension.…”

“…Several studies have evidenced increased levels of copeptin in different pathological conditions, such as metabolic syndrome, chronic kidney disease, and hypertension. 3 In particular, copeptin levels have been associated with office BP and ambulatory BP, resistant hypertension, and essential hypertension in adolescents, 4 suggesting a certain role in arterial hypertension. Various mechanisms are thought to be involved, such as the local tissue RAAS activation in hypothalamus that stimulates vasopressin secretion, or an enhanced vasoconstriction, 4 or an increased tubular sodium retention.…”

Copeptin is independently associated with vascular calcification in chronic kidney disease stage 5

“…High circulating copeptin is associated with decline in glomerular filtration rate and a greater risk of new-onset CKD [16,17]. Moreover, high copeptin has been linked with increased risk of myocardial infarction, heart failure, hypertension, ischemic stroke, diabetes mellitus and metabolic syndrome [14,18]. In patients with type 1 diabetes, elevated copeptin levels were strongly related to diabetic CKD and coronary atherosclerosis [19].…”