Serum Sclerostin as an Independent Marker of Peripheral Arterial Stiffness in Renal Transplantation Recipients

Abstract

Wnt/β-catenin signaling pathway is thought to be implicated in the development of arterial stiffness and vascular calcification. As a Wnt signaling pathway inhibitor, it is interesting to investigate whether sclerostin or dickkopf-1 (DKK1) level is correlated with arterial stiffness in renal transplant (RT) recipients. Fasting blood samples were obtained for biochemical data, sclerostin, DKK1, and osteoprotegerin (OPG) determinations. In this study, we applied automatic pulse wave analyzer (VaSera VS-1000) to measure brachial-ankle pulse wave velocity and either sides of brachial-ankle pulse wave velocity value, which greater than 14.0 m/s was determined as high arterial stiffness. Among 68 RT recipients, 30 patients (44.1%) were in the high arterial stiffness group. Compared with patients in the low arterial stiffness group, patients in the high arterial stiffness group had higher prevalence of hypertension (P = 0.002), diabetes (P < 0.001), metabolic syndrome (P = 0.025), longer posttransplant duration (P = 0.005), higher systolic blood pressure (P < 0.001) and diastolic blood pressure (P = 0.018), and higher fasting glucose (P = 0.004), total cholesterol (P = 0.042), blood urea nitrogen (P = 0.020), phosphorus (P = 0.042), and sclerostin levels (P = 0.001). According to our multivariable forward stepwise linear regression analysis, age (β = 0.272, P = 0.014), phosphorus (β = 0.308, P = 0.007), and logarithmically-transformed OPG (log-OPG; β = 0.222, P = 0.046) were positively associated with sclerostin levels, and multivariate logistic regression analysis, sclerostin (odds ratio 1.052, 95% confidence interval 1.007–1.099, P = 0.024), and posttransplant duration (odds ratio 1.024, 95% confidence interval 1.004–1.045, P = 0.019) were the independent predictors of peripheral arterial stiffness in RT recipients. In this study, serum sclerostin level, but not DKK1, was proved to be involved in the pathogenetic process of peripheral arterial stiffness in RT recipients.

Levels of serum sclerostin, metabolic parameters, and periodontitis in ­postmenopausal women with diabetes

“…Such disorders include osteosclerosis and sclerosing dysplasias due to a deficiency of sclerostin, which is a protein secreted by osteocytes that inhibits bone formation and has the capacity to induce apoptosis in osteoblasts . Sclerostin is an inhibitor of Wnt/β‐catenin signaling and exerts a negative effect on bone formation, contributing to the loss of alveolar bone induced by periodontal disease –. Sclerostin is encoded by the SOST gene and impedes the proliferation and function of osteoblasts, thereby diminishing bone formation – through the interruption of Wnt signaling by binding with the Wnt coreceptor, which is a receptor of low‐density lipoprotein (LDL) .…”

Disorders in the System of Mineral and Bone Metabolism Regulators—FGF-23, Klotho and Sclerostin—in Chronic Kidney Disease: Clinical Significance and Possibilities for Correction

“…At the same time, the frequency of ABD associated with a relatively low PTH and high sclerostin serum levels increases [12,24,27]. These changes, together with a decreased calcium excretion, may be responsible for the development of such complications of CKD as renal osteodystrophy, cardiovascular calcification following CVC and adverse outcomes in CKD [6,7,26].…”

“…It is important to determine the clinical significance of changes in sclerostin metabolism in CKD, because the relationship between adynamic bone disease (ABD) and calcification of the heart and blood vessels in patients with CKD is considered proven [27]. At the same time, available-to-date publications on the role of sclerostin in ectopic calcification still remain contradictory [22,23,25,26].…”

“…To date, sclerostin is an established regulator of bone mineralization, while its role in the pathophysiology of vessels in CKD is actively explored [22,26]. It is important to determine the clinical significance of changes in sclerostin metabolism in CKD, because the relationship between adynamic bone disease (ABD) and calcification of the heart and blood vessels in patients with CKD is considered proven [27].…”

“…According to the results of recent studies, a disorder of the FGF-23-Klotho-sclerostin ratio in CKD is an early biomarker of the degree of chronic renal damage, preceded to the changes in other established markers of CKD advancement such as hyperphosphatemia, hyperparathyroidism and hypovitaminosis D, considering early as emerging cardiovascular risk factors in CKD patients [5,26]. In addition, in interventional trials, intake of phosphate binders, cinacalcet or active vitamin D did not exert a consistently beneficial effect to reduce in cardiovascular event rate [28].…”