Eirini Stavrinou1, Pantelis A Sarafidis2, Charalampos Koumaras3, Charalampos Loutradis1, Panagiotis Giamalis1, Konstantinos Tziomalos4, Asterios Karagiannis3, Aikaterini Papagianni1. 1. Department of Nephrology, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece. 2. Department of Nephrology, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece, psarafidis11@yahoo.gr. 3. Second Propaedeutic Department of Internal Medicine, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece. 4. First Propaedeutic Department of Internal Medicine, AHEPA Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.
Abstract
BACKGROUND: Sclerostin and Dickkopf-1 (Dkk-1) proteins are inhibitors of the canonical Wnt/β-catenin bone pathway. Pilot data suggest that sclerostin may be involved in vascular changes in chronic kidney disease (CKD), but data on the effects of Dkk-1 are scarce. This is the first study investigating simultaneously the associations of sclerostin and Dkk-1 with arterial stiffness in hemodialysis patients. METHODS: A total of 80 patients on chronic hemodialysis had carotid-femoral pulse wave velocity (PWV), central blood pressure (BP), and wave reflections evaluated with applanation tonometry (Sphygmocor) on a midweek non-dialysis day. Serum levels of sclerostin and Dkk-1 were measured with ELISA. A large set of demographic, comorbid, laboratory, and drug parameters were used in the analyses. RESULTS: Subjects with PWV >9.5 m/s (high arterial stiffness group, n = 40) were older, had higher BMI, higher prevalence of hypertension, diabetes, and coronary heart disease, and higher peripheral systolic BP, central systolic BP, C-reactive protein, and serum sclerostin (p = 0.02), but similar Dkk-1, compared to subjects with low PWV. When dichotomizing the population by sclerostin levels, those with high sclerostin had higher PWV than patients with low sclerostin levels (10.63 ± 2.71 vs. 9.77 ± 3.13, p = 0.048). Increased sclerostin (>200 pg/mL) was significantly associated with increased PWV (>9.5 m/s; HR 2.778, 95% CI 1.123-6.868 per pg/mL increase); this association remained significant after stepwise adjustment for Dkk-1, intact parathyroid hormone, and calcium × phosphate product. In contrast, no association was noted between Dkk-1 and PWV (HR 1.000, 95% CI 0.416-2.403). CONCLUSION: Serum sclerostin is associated with PWV independently of routine markers of CKD-MBD in hemodialysis patients. In contrast, Dkk-1 has no association with arterial stiffness and is not pathophysiologically involved in relevant vascular changes.
BACKGROUND:Sclerostin and Dickkopf-1 (Dkk-1) proteins are inhibitors of the canonical Wnt/β-catenin bone pathway. Pilot data suggest that sclerostin may be involved in vascular changes in chronic kidney disease (CKD), but data on the effects of Dkk-1 are scarce. This is the first study investigating simultaneously the associations of sclerostin and Dkk-1 with arterial stiffness in hemodialysis patients. METHODS: A total of 80 patients on chronic hemodialysis had carotid-femoral pulse wave velocity (PWV), central blood pressure (BP), and wave reflections evaluated with applanation tonometry (Sphygmocor) on a midweek non-dialysis day. Serum levels of sclerostin and Dkk-1 were measured with ELISA. A large set of demographic, comorbid, laboratory, and drug parameters were used in the analyses. RESULTS: Subjects with PWV >9.5 m/s (high arterial stiffness group, n = 40) were older, had higher BMI, higher prevalence of hypertension, diabetes, and coronary heart disease, and higher peripheral systolic BP, central systolic BP, C-reactive protein, and serum sclerostin (p = 0.02), but similar Dkk-1, compared to subjects with low PWV. When dichotomizing the population by sclerostin levels, those with high sclerostin had higher PWV than patients with low sclerostin levels (10.63 ± 2.71 vs. 9.77 ± 3.13, p = 0.048). Increased sclerostin (>200 pg/mL) was significantly associated with increased PWV (>9.5 m/s; HR 2.778, 95% CI 1.123-6.868 per pg/mL increase); this association remained significant after stepwise adjustment for Dkk-1, intact parathyroid hormone, and calcium × phosphate product. In contrast, no association was noted between Dkk-1 and PWV (HR 1.000, 95% CI 0.416-2.403). CONCLUSION: Serum sclerostin is associated with PWV independently of routine markers of CKD-MBD in hemodialysis patients. In contrast, Dkk-1 has no association with arterial stiffness and is not pathophysiologically involved in relevant vascular changes.