Sclerostin Serum Levels and Vascular Calcification Progression in Prevalent Renal Transplant Recipients
Sclerostin Serum Levels and Vascular Calcification Progression in Prevalent Renal Transplant Recipients
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DOI：
10.1210/jc.2015-3056
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发表时间：
2015-12-01
影响因子：
5.8
通讯作者：
Jadoul, M.
中科院分区：
文献类型：
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作者：
Evenepoel, P.;Goffin, E.;Jadoul, M.
背景：血管钙化（VC）在肾移植受者（RTRs）中普遍存在且呈进行性。最近的横截面数据表明，激活Wnt信号有助于VC。目的：目的是调查Wnt拮抗剂sclerostin的循环水平是否与VC的进展相关。设计：这是一项纵向观察性布鲁塞尔肾移植队列研究的事后分析。设置：设置为三级护理学术医院。患者：通过多层螺旋CT测量了268例RTR患者（年龄53 ± 13岁; 61%为男性）的冠状动脉钙化和主动脉钙化，并在中位随访4.4年后对189例患者进行了重新测量。在储存的血液样品上评估基线血清硬化蛋白水平。进行回归分析，以确定基线VC和progression.Main结果measure的决定因素：主要结果的措施是进展的VC。结果：VC是目前在84%的参与者在基线。根据Hokanson标准，几乎一半的患者显示VC进展。基线时的横断面分析表明，单变量分析中sclerostin水平与VC评分之间存在直接相关性，在调整年龄、性别和PTH水平后，该相关性变为负相关。值得注意的是，在最终回归模型中，较低的硬化蛋白水平被确定为较高的基线主动脉钙化评分的独立决定因素。此外，基线sclerostin水平与VC进展呈负相关，至少在调整传统的风险factors.Conclusions：血清sclerostin水平呈负相关，VC负担和进展后，在流行的RTRs调整传统的风险因素。我们的数据证实了以前在非移植慢性肾脏病患者中的发现，并支持硬化蛋白可能在VC过程中作为抑制VC的局部反调节机制的一部分在血管壁中上调的观点。需要额外的临床和实验数据进行确认。
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.