Abstract

PurposeSclerostin is an antagonist of the Wnt/β-catenin pathway. We previously reported that sclerostin is closely related to carotid artery atherosclerosis and long-term outcome in hemodialysis patients. The present study investigated the association between sclerostin, renal function, and carotid artery atherosclerosis in non-dialysis patients with stage 3–5 chronic kidney disease (CKD 3–5ND).MethodsA total of 140 patients with CKD 3–5ND were enrolled in this cross-sectional study. The Chronic Kidney Disease Epidemiology Collaboration equation was used to calculate estimated glomerular filtration rate (eGFR). Atherosclerotic plaques in the carotid artery were detected by B-mode Doppler ultrasound. Blood samples were collected to assess serum sclerostin levels. Unconditional logistic regression analysis was used to identify risk factors for carotid atherosclerotic plaques.ResultsThe median eGFR was 24.9 ml/min/1.73 m2 (interquartile range [IQR] 10.0–40.3 ml/min/1.73 m2) and median serum sclerostin level was 46.76 pmol/l (IQR 30.18–67.56 pmol/l). Carotid atherosclerotic plaques were detected in 104 subjects (74.3%). There was a negative association between sclerostin level and eGFR (r = − 0.214, p = 0.011). Unconditional logistic regression analysis revealed that sclerostin level was an independent risk factor for the occurrence of carotid plaques, with an odds ratio (95% confidence interval) of 1.026 (1.003, 1.051).ConclusionSerum sclerostin increases with declining renal function in patients with CKD 3–5ND. Sclerostin is an independent risk factor for carotid atherosclerosis.

Highlights

  • Cardiovascular disease is more prevalent in patients with chronic kidney disease (CKD) than in the general population [1, 2]

  • Sclerostin encoded by the SOST gene is an antagonist of the Wnt/β-catenin pathway that is mainly secreted by osteoblasts and inhibits bone formation [6]

  • Sclerostin levels were comparable between patients with and those without diabetes mellitus (DM) (47.28 vs 45.75 pmol/l; median, p = 0.273)

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Summary

Introduction

Cardiovascular disease is more prevalent in patients with chronic kidney disease (CKD) than in the general population [1, 2]. The Wnt-β-catenin signaling pathway is an important player in bone remodeling, and is involved in osteoblast proliferation, differentiation and bone formation [6, 7]. Dysregulation of the Wnt-β-catenin pathway plays a crucial role in chronic kidney disease–mineral bone disorder (CKD-MBD) [6]. Sclerostin encoded by the SOST gene is an antagonist of the Wnt/β-catenin pathway that is mainly secreted by osteoblasts and inhibits bone formation [6]. Serum levels of sclerostin are higher in CKD patients than in the general population and begin increasing during stage 3 [11]. It remains unclear how increased sclerostin relates to abnormalities in bone turnover in CKD patients

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