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

ABSTRACT: BACKGROUND:Vascular calcification (VC) is an independent predictor of cardiovascular disease (CVD) present in 30-70% of patients with chronic kidney disease (CKD). Copeptin is a sensitive surrogate marker of arginine vasopressin (AVP), which is involved in many pathophysiologic processes in CKD. The aim of the present study was to explore the association of copeptin with VC in CKD stage 5. METHODS:Copeptin was investigated in conjunction with living donor kidney transplantation in 149 clinically stable CKD stage 5 patients (CKD5), including 53 non-dialyzed (CKD5-ND) and 96 dialysis patients treated by peritoneal dialysis (PD) (n?=?43) or hemodialysis (HD) (n?=?53). We analyzed the association of copeptin with presence and extent of VC ascertained both histologically in biopsies from the inferior epigastric artery (n?=?137) and by coronary artery calcification (CAC) score measured by computed tomography. RESULTS:Patients with higher copeptin were older, had higher systolic blood pressure, higher prevalence of CVD and their preceding time on chronic dialysis was longer. In Spearman's rank correlations (Rho), copeptin concentrations were significantly associated with CAC score (Rho?=?0.27; p?=?0.003) and presence of medial VC (Rho?=?0.21; p?=?0.016). Multivariate logistic regression analysis showed that 1-SD higher age, male gender, diabetes and 1-SD higher copeptin were significantly associated with the presence of moderate-extensive VC. CONCLUSIONS:High circulating levels of copeptin in CKD5 patients are independently associated with the degree of medial calcification ascertained by histology of arterial biopsies. Thus, plasma copeptin may serve as a marker of the uremic calcification process.

SUBMITTER: Golembiewska E

PROVIDER: S-EPMC7006395 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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

Golembiewska Edyta E Qureshi Abdul Rashid AR Dai Lu L Lindholm Bengt B Heimbürger Olof O Söderberg Magnus M Brismar Torkel B TB Ripsweden Jonaz J Barany Peter P Johnson Richard J RJ Stenvinkel Peter P

BMC nephrology 20200207 1

<h4>Background</h4>Vascular calcification (VC) is an independent predictor of cardiovascular disease (CVD) present in 30-70% of patients with chronic kidney disease (CKD). Copeptin is a sensitive surrogate marker of arginine vasopressin (AVP), which is involved in many pathophysiologic processes in CKD. The aim of the present study was to explore the association of copeptin with VC in CKD stage 5.<h4>Methods</h4>Copeptin was investigated in conjunction with living donor kidney transplantation in ...[more]

PMID: 32033584

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Project description:An association between lower bone mineral density (BMD) and presence of vascular calcification (VC) has been reported in several studies. Chronic kidney disease (CKD) causes detrimental disturbances in the mineral balance, bone turnover, and development of severe VC. Our group has previously demonstrated expression of Wnt inhibitors in calcified arteries of CKD rats. Therefore, we hypothesized that the CKD-induced VC via this pathway signals to bone and induces bone loss. To address this novel hypothesis, we developed a new animal model using isogenic aorta transplantation (ATx). Severely calcified aortas from uremic rats were transplanted into healthy rats (uremic ATx). Transplantation of normal aortas into healthy rats (normal ATx) and age-matched rats (control) served as control groups. Trabecular tissue mineral density, as measured by μCT, was significantly lower in uremic ATx rats compared with both control groups. Uremic ATx rats showed a significant upregulation of the mineralization inhibitors osteopontin and progressive ankylosis protein homolog in bone. In addition, we found significant changes in bone mRNA levels of several genes related to extracellular matrix, bone turnover, and Wnt signaling in uremic ATx rats, with no difference between normal ATx and control. The bone histomorphometry analysis showed significant lower osteoid area in uremic ATx compared with normal ATx along with a trend toward fewer osteoblasts as well as more osteoclasts in the erosion lacunae. Uremic ATx and normal ATx had similar trabecular number and thickness. The bone formation rate did not differ between the three groups. Plasma biochemistry, including sclerostin, kidney, and mineral parameters, were similar between all three groups. ex vivo cultures of aorta from uremic rats showed high secretion of the Wnt inhibitor sclerostin. In conclusion, the presence of VC lowers BMD, impairs bone metabolism, and affects several pathways in bone. The present results prove the existence of a vasculature to bone tissue cross-talk. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

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

Publications

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

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