Department of Medicine, Division of Nephrology and Multiorgan Transplant Program, University Health Network, University of Toronto, Toronto, ON, Canada.
Nephrology Division, Uzsoki Teaching Hospital, Budapest, Hungary.
Transpl Int. 2021 May;34(5):844-854. doi: 10.1111/tri.13847. Epub 2021 Mar 18.
Paradoxically, higher serum levels of osteoprotegerin (OPG: a vascular calcification inhibitor) have been associated with increased arterial stiffness, risk of cardiovascular disease and all-cause mortality. A few studies reported that post-transplant OPG levels are associated with mortality in kidney transplant (KT) recipients. In this study, this association was assessed in a cohort of prevalent KT recipients, adjusting for previously untested potential confounders, including fibroblast growth factor 23 (FGF23) and interleukin 6 (IL-6). Socio-demographic and clinical parameters, medical and transplant history, and laboratory data were collected from 982 prevalent KT recipients. The association between serum OPG and all-cause mortality over a 6-year follow-up period was examined using Kaplan-Meier survival curves and multivariable-adjusted Cox regression models. Participants with high serum OPG were more likely female, older, deceased donor KT recipients and have more comorbidity, lower eGFR, higher FGF23, higher IL-6, and longer dialysis vintage. Each 1 pmol/l higher serum OPG level was associated with a 49% higher risk of mortality (hazard ratio (HR) [95% confidence interval (CI)]: 1.49 [1.40-1.61]). This association persisted after adjusting for confounders (HR [95% CI]: 1.20 [1.10-1.30]). In conclusion, serum OPG was associated with all-cause mortality independent of several novel confounders in prevalent KT recipients.
具有讽刺意味的是，较高的血清骨保护素（OPG：一种血管钙化抑制剂）水平与动脉僵硬、心血管疾病风险和全因死亡率增加有关。一些研究报告称，移植后 OPG 水平与肾移植（KT）受者的死亡率有关。在这项研究中，在一组现患 KT 受者中评估了这种相关性，调整了以前未经测试的潜在混杂因素，包括成纤维细胞生长因子 23（FGF23）和白细胞介素 6（IL-6）。从 982 名现患 KT 受者中收集了社会人口统计学和临床参数、医疗和移植史以及实验室数据。使用 Kaplan-Meier 生存曲线和多变量调整 Cox 回归模型检查了血清 OPG 与 6 年随访期间全因死亡率之间的关系。高血清 OPG 组更可能是女性、年龄较大、已故供体 KT 受者，并且合并症更多、eGFR 更低、FGF23 更高、IL-6 更高、透析时间更长。血清 OPG 每增加 1 pmol/l，死亡率就会增加 49%（风险比 (HR) [95% 置信区间 (CI)]：1.49 [1.40-1.61]）。在调整混杂因素后（HR [95% CI]：1.20 [1.10-1.30]），这种相关性仍然存在。总之，血清 OPG 与全因死亡率相关，与现患 KT 受者中的几个新混杂因素无关。
