Division of Nephrology, Kaohsiung Veterans General Hospital, No.386, Dazhong 1st Rd., Zuoying Dist, Kaohsiung City, 81362, Taiwan.
Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan.
BMC Nephrol. 2019 Sep 2;20(1):345. doi: 10.1186/s12882-019-1543-3.
Patients with end-stage renal disease have a higher risk of death from cardiovascular events, which can be mainly attributed to coronary artery calcification (CAC). Wnt signaling is involved in vascular development and may play a role in vascular calcification. This study aimed to evaluate CAC prevalence in patients on dialysis with severe secondary hyperparathyroidism (SHPT) and identify CAC risk factors.
The study is a retrospective analysis of the severe hyperparathyroidism registration study that prospectively recruited patients on dialysis with severe SHPT who were candidates for parathyroidectomy, from October 2013 to May 2015. CAC and bone mineral density (BMD) were measured. Demographic and clinical data including calcium, phosphorus, alkaline phosphatase, intact parathyroid hormone, Dickkopf-related protein 1 (DKK1), and sclerostin levels were analyzed. CAC scores were reported in Agatston units (AU).
A total of 61 patients were included in this study. No CAC, mild CAC (<100 AU), moderate CAC (>100 AU), and severe CAC (>400 AU) were observed in 4.9%, 11.4%, 14.8%, and 68.9% of patients, respectively. DKK1 and sclerostin were not associated with CAC. In univariate analysis, CAC was significantly correlated with age, sex (male), total cholesterol, and intravenous pulse calcitriol (p<0.05). CAC was not inversely correlated with the BMD, T scores, or Z scores of the femoral neck (p>0.05). In multivariate analysis, the stepwise forward multiple linear regression revealed that CAC was associated with age, male sex and intravenous pulse calcitriol (p<0.05). Furthermore, serum sclerostin was positively correlated with the BMD of the femoral neck but negatively associated with intact parathyroid hormone (p<0.05). Serum sclerostin was significantly associated with severely low bone mass with Z-scores<-2.5 of the femoral neck, even when adjusted for serum intact parathyroid hormone, vitamin D status, dialysis pattern, sex, and DKK-1 (p<0.05).
The patients on dialysis with severe SHPT have a high prevalence of vascular calcification. Although the Wnt signaling pathway could play a role in hyperparathyroid bone disease, CAC may be mainly due to the treatment modality rather than the Wnt signaling pathway associated bone metabolism in patients on dialysis with severe SHPT.
终末期肾病患者死于心血管事件的风险较高，这主要归因于冠状动脉钙化（CAC）。Wnt 信号通路参与血管发育，可能在血管钙化中发挥作用。本研究旨在评估透析伴严重继发性甲状旁腺功能亢进症（SHPT）患者 CAC 的患病率，并确定 CAC 的危险因素。
本研究为前瞻性招募 2013 年 10 月至 2015 年 5 月行甲状旁腺切除术的透析伴严重 SHPT 候选患者的严重甲状旁腺功能亢进登记研究的回顾性分析。测量 CAC 和骨密度（BMD）。分析包括钙、磷、碱性磷酸酶、全段甲状旁腺激素、Dickkopf 相关蛋白 1（DKK1）和骨硬化蛋白水平在内的人口统计学和临床数据。CAC 评分以 Agatston 单位（AU）报告。
本研究共纳入 61 例患者。分别有 4.9%、11.4%、14.8%和 68.9%的患者无 CAC、轻度 CAC（<100 AU）、中度 CAC（>100 AU）和重度 CAC（>400 AU）。DKK1 和骨硬化蛋白与 CAC 无关。在单因素分析中，CAC 与年龄、性别（男性）、总胆固醇和静脉脉冲骨化三醇显著相关（p<0.05）。CAC 与股骨颈的 BMD、T 评分或 Z 评分无负相关（p>0.05）。多因素分析中，逐步向前多元线性回归显示 CAC 与年龄、男性和静脉脉冲骨化三醇相关（p<0.05）。此外，血清骨硬化蛋白与股骨颈 BMD 呈正相关，与全段甲状旁腺激素呈负相关（p<0.05）。血清骨硬化蛋白与股骨颈 Z 评分<-2.5 的严重低骨量显著相关，即使在调整全段甲状旁腺激素、维生素 D 状态、透析模式、性别和 DKK-1 后也是如此（p<0.05）。
透析伴严重 SHPT 患者的血管钙化患病率较高。尽管 Wnt 信号通路可能在甲状旁腺亢进性骨病中发挥作用，但 CAC 可能主要与透析伴严重 SHPT 患者的治疗方式而非 Wnt 信号通路相关的骨代谢有关。
