P1270INCREASED SCLEROSTIN, BUT NOT DKK-1 PROTEIN, IS ASSOCIATED WITH ELEVATED PULSE WAVE VELOCITY IN HEMODIALYSIS SUBJECTS

Background and Aims Sclerostin and Dickkopf-1 (Dkk-1) protein are inhibitors of the canonical Wnt/β-catenin bone pathway. Pilot data suggest that sclerostin may be involved in vascular changes in CKD, but data on Dkk-1 effects are scarce. This is the first study investigating simultaneously the associations of sclerostin and Dkk-1 with arterial stiffness in hemodialysis patients. Method 80 patients on chronic hemodialysis had carotid-femoral pulse wave velocity (PWV), central BP and wave reflections evaluated with applanation tonometry (Sphygmocor) in a mid-week non-dialysis day. Serum levels of sclerostin and Dkk-1 were measured with ELISA. A large set of demographic, co-morbid, laboratory and drug parameters were used in the analyses. Results Subjects with PWV>9.5 m/sec (high arterial stiffness group, n=40) were older, had higher BMI, higher prevalence of hypertension, diabetes and coronary-heart-disease and higher peripheral SBP, central SBP, 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, iPTH and calcium x 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 rather not pathophysiologically involved in relevant vascular changes.