Sclerostin Serum Levels and Vascular Calcification Progression in Prevalent Renal Transplant Recipients.
BACKGROUND
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.


METHODS
This was a post hoc analysis of the longitudinal observational Brussels Renal Transplant Cohort study.


METHODS
The setting was a tertiary care academic hospital.


METHODS
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.


METHODS
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.
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.
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Evenepoel
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.
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Goffin
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.
B
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Meijers
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.
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Kanaan
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.
B
B
Bammens
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.
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Coche
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.
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Claes
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.
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M
Jadoul
D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D001011:Aorta / Q000473:pathology; D019485:Bone Morphogenetic Proteins / Q000097:blood*; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D005819:Genetic Markers; D006801:Humans; D016030:Kidney Transplantation; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D014057:Tomography, X-Ray Computed; D066027:Transplant Recipients; D061205:Vascular Calcification / Q000097:blood* / Q000473:pathology
D048868:Adaptor Proteins, Signal Transducing; D019485:Bone Morphogenetic Proteins; D005819:Genetic Markers; C422903:SOST protein, human