P Evenepoel1, E Goffin1, B Meijers1, N Kanaan1, B Bammens1, E Coche1, K Claes1, M Jadoul1. 1. Laboratory of Nephrology (P.E., B.M., B.B., K.C.), Department of Immunology and Microbiology, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium; and Divisions of Nephrology (E.G., N.K., M.J.) and Medical Imaging (E.C.), Cliniques Universitaires Saint Luc, Université Catholique de Louvain, B-1200 Brussels, Belgium.
Abstract
CONTEXT: Vascular calcification (VC) is prevalent and progressive in renal transplant recipients (RTRs). Recent cross-sectional data suggest that activated Wnt signaling contributes to VC. OBJECTIVE: The objective was to investigate whether circulating levels of the Wnt antagonist sclerostin associate with progression of VC. DESIGN: This was a post hoc analysis of the longitudinal observational Brussels Renal Transplant Cohort study. SETTING: The setting was a tertiary care academic hospital. PATIENTS: Coronary artery calcification and aorta calcification were measured by multislice spiral computerized tomography in 268 prevalent RTRs (age, 53 ± 13 y; 61% male) at baseline and remeasured in 189 patients after a median follow-up of 4.4 years. Baseline serum sclerostin levels were assessed on stored blood samples. Regression analysis was performed to identify determinants of baseline VC and progression. MAIN OUTCOME MEASURE: The main outcome measure was progression of VC. RESULTS: VC was present in up to 84% of participants at baseline. Almost half of the patients showed progression of VC, according to Hokanson criteria. The cross-sectional analysis at baseline demonstrated a direct association between sclerostin levels and VC score in univariate analysis, which became inverse after adjustment for age, gender and PTH level. Remarkably, a lower sclerostin level was identified as an independent determinant of a higher baseline aorta calcification score in the final regression model. Moreover, baseline sclerostin levels showed an inverse association with VC progression, at least after adjustment for traditional risk factors. CONCLUSIONS: Serum sclerostin levels inversely associated with VC burden and progression in prevalent RTRs after adjustment for traditional risk factors. Our data corroborate previous findings in nontransplanted chronic kidney disease patients and support the notion that sclerostin may be up-regulated in the vascular wall during the VC process as part of a local counterregulatory mechanism directed to suppress VC. Additional clinical and experimental data are required for confirmation.
CONTEXT: Vascular calcification (VC) is prevalent and progressive in renal transplant recipients (RTRs). Recent cross-sectional data suggest that activated Wnt signaling contributes to VC. OBJECTIVE: The objective was to investigate whether circulating levels of the Wnt antagonist sclerostin associate with progression of VC. DESIGN: This was a post hoc analysis of the longitudinal observational Brussels Renal Transplant Cohort study. SETTING: The setting was a tertiary care academic hospital. PATIENTS: Coronary artery calcification and aorta calcification were measured by multislice spiral computerized tomography in 268 prevalent RTRs (age, 53 ± 13 y; 61% male) at baseline and remeasured in 189 patients after a median follow-up of 4.4 years. Baseline serum sclerostin levels were assessed on stored blood samples. Regression analysis was performed to identify determinants of baseline VC and progression. MAIN OUTCOME MEASURE: The main outcome measure was progression of VC. RESULTS: VC was present in up to 84% of participants at baseline. Almost half of the patients showed progression of VC, according to Hokanson criteria. The cross-sectional analysis at baseline demonstrated a direct association between sclerostin levels and VC score in univariate analysis, which became inverse after adjustment for age, gender and PTH level. Remarkably, a lower sclerostin level was identified as an independent determinant of a higher baseline aorta calcification score in the final regression model. Moreover, baseline sclerostin levels showed an inverse association with VC progression, at least after adjustment for traditional risk factors. CONCLUSIONS: Serum sclerostin levels inversely associated with VC burden and progression in prevalent RTRs after adjustment for traditional risk factors. Our data corroborate previous findings in nontransplanted chronic kidney diseasepatients and support the notion that sclerostin may be up-regulated in the vascular wall during the VC process as part of a local counterregulatory mechanism directed to suppress VC. Additional clinical and experimental data are required for confirmation.
Authors: Matthew T Drake; Jennifer S Fenske; Frank A Blocki; Claudia Zierold; Natasha Appelman-Dijkstra; Socrates Papapoulos; Sundeep Khosla Journal: Bone Date: 2018-03-14 Impact factor: 4.398