Department of Internal Medicine, Hospital de Clínicas, Federal University of Paraná, General Carneiro, 181, Curitiba, PR, 80060-900, Brazil.
Divisions of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institute, Karolinska University Hospital in Huddinge, Stockholm, Sweden.
Sci Rep. 2021 Jan 28;11(1):2473. doi: 10.1038/s41598-021-82072-z.
Cardiovascular disease (CVD) is the leading cause of death in patients with chronic kidney disease (CKD). Osteoprotegerin (OPG), known to regulate bone mass by inhibiting osteoclast differentiation and activation, might also play a role in vascular calcification. Increased circulating OPG levels in patients with CKD are associated with aortic calcification and increased mortality. We assessed the predictive role of OPG for all-cause and cardiovascular mortality in patients with CKD stages 3-5 over a 5-year follow-up period. We evaluated the relationship between OPG and all-cause and cardiovascular mortality in 145 CKD patients (stages 3-5) in a prospective observational follow-up study. Inflammation markers, including high-sensitivity C-reactive protein, standard echocardiography, and estimation of intima-media thickness in the common carotid artery, were assessed at baseline, and correlations with OPG levels were determined. The cutoff values for OPG were defined using ROC curves for cardiovascular mortality. Survival was assessed during follow up lasting for up to 5.5 years using Fine and Gray model. A total of 145 (89 men; age 58.9 ± 15.0 years) were followed up. The cutoff value for OPG determined using ROC was 10 pmol/L for general causes mortality and 10.08 pmol/L for CV causes mortality. Patients with higher serum OPG levels presented with higher mortality rates compared to patients with lower levels. Aalen-Johansen cumulative incidence curve analysis demonstrated significantly worse survival rates in individuals with higher baseline OPG levels for all-cause and cardiovascular mortality (p < 0.001). In multivariate analysis, OPG was a marker of general and cardiovascular mortality independent of sex, age, CVD, diabetes, and CRP levels. When CKD stages were included in the multivariate analysis, OPG was an independent marker of all-cause mortality but not cardiovascular mortality. Elevated serum OPG levels were associated with higher all-cause and cardiovascular mortality risk, independent of age, CVD, diabetes, and inflammatory markers, in patients with CKD.
心血管疾病（CVD）是慢性肾脏病（CKD）患者死亡的主要原因。骨保护素（OPG）通过抑制破骨细胞分化和激活来调节骨量，它也可能在血管钙化中发挥作用。CKD 患者循环 OPG 水平升高与主动脉钙化和死亡率增加有关。我们评估了 OPG 在 CKD 3-5 期患者 5 年随访期间全因和心血管死亡率的预测作用。我们在一项前瞻性观察随访研究中评估了 145 例 CKD 患者（3-5 期）中 OPG 与全因和心血管死亡率之间的关系。在基线时评估炎症标志物，包括高敏 C 反应蛋白、标准超声心动图和颈总动脉内膜中层厚度的估计，并确定与 OPG 水平的相关性。使用 ROC 曲线为心血管死亡率定义 OPG 的截断值。使用 Fine 和 Gray 模型在长达 5.5 年的随访期间评估生存情况。共有 145 例（89 例男性；年龄 58.9±15.0 岁）接受了随访。使用 ROC 确定的 OPG 截断值为全因死亡率 10pmol/L，心血管死亡率 10.08pmol/L。与 OPG 水平较低的患者相比，血清 OPG 水平较高的患者死亡率更高。Aalen-Johansen 累积发病率曲线分析表明，全因和心血管死亡率的基线 OPG 水平较高的个体的生存率显著较低（p<0.001）。多变量分析表明，OPG 是全因和心血管死亡率的标志物，独立于性别、年龄、CVD、糖尿病和 CRP 水平。当将 CKD 分期纳入多变量分析时，OPG 是全因死亡率的独立标志物，但不是心血管死亡率的独立标志物。在 CKD 患者中，血清 OPG 水平升高与全因和心血管死亡率风险增加相关，独立于年龄、CVD、糖尿病和炎症标志物。
