Area of Cardiometabolic and Renal Risk, Institute for Biomedical Research INCLIVA, Valencia, Spain.
Hypertension Unit, Department of Internal Medicine, University Hospital Clínico of Valencia, Valencia, Spain.
Nephrol Dial Transplant. 2017 Sep 1;32(9):1566-1578. doi: 10.1093/ndt/gfw387.
Patients undergoing hemodialysis and kidney graft recipients are high-risk populations for cardiovascular and all-cause mortality. Fibroblast growth factor 23 (FGF23), osteoprotegerin (OPG), RANK ligand, osteopontin (OPN), Klotho protein and bone morphogenetic protein-7 (BMP-7) are bone- and vascular-derived molecular biomarkers that have been shown to be associated with cardiovascular surrogate end points; however, currently available data on the prognostic value of these biomarkers is inconsistent. The aim of the present study was to conduct a systematic review and meta-analysis in order to summarize the available evidence on the association of molecular biomarkers with mortality in individuals undergoing hemodialysis and renal transplant patients.
Two databases (MEDLINE and Embase) were systematically searched. Studies were eligible if the association of biomarker and mortality was reported as time-to-event data [hazard Ratio (HR)] or as effect size with a fixed time of follow-up [odds Ratio (OR)]. Abstracted HRs were converted onto a standard scale of effect and combined using a random effects model.
From a total of 1170 studies identified in initial searches, 21 met the inclusion criteria. In hemodialysis patients, comparing the lower third with the upper third of baseline FGF23 distribution, pooled HRs (95% confidence intervals) were 1.94 (1.47, 2.56) for all-cause mortality and 2.4 (1.64, 3.51) for cardiovascular mortality. For the same comparison of baseline OPG distribution, pooled HRs were 1.8 (0.95, 3.39) for all-cause mortality and 2.53 (1.29, 4.94) for cardiovascular mortality. Reported risk estimates of RANK ligand, OPN, Klotho protein and BMP-7 were not suitable for pooling; however, only Klotho protein was significantly related to mortality. For kidney graft recipients, four studies that investigated the relationship of FGF23 and OPG with mortality were identified, all of which reported a significant association.
In hemodialysis patients, FGF23 is a predictor of all-cause and cardiovascular mortality, whereas the predictive value of OPG is restricted to cardiovascular mortality. Further studies are needed in order to gain insight into the prognostic value of these biomarkers in renal transplant recipients.
血液透析患者和肾移植受者是心血管疾病和全因死亡率的高危人群。成纤维细胞生长因子 23（FGF23）、护骨素（OPG）、RANK 配体、骨桥蛋白（OPN）、Klotho 蛋白和骨形成蛋白-7（BMP-7）是骨和血管来源的分子生物标志物，已被证明与心血管替代终点相关；然而，目前这些生物标志物预后价值的相关数据并不一致。本研究旨在进行系统评价和荟萃分析，以总结关于血液透析患者和肾移植患者中分子标志物与死亡率之间关系的现有证据。
系统检索了两个数据库（MEDLINE 和 Embase）。如果将生物标志物与死亡率的关联报告为时间事件数据[风险比（HR）]或作为固定随访时间的效应大小[比值比（OR）]，则研究符合纳入标准。提取的 HR 被转换为标准效应尺度，并使用随机效应模型进行合并。
从最初搜索中总共确定了 1170 项研究，其中 21 项符合纳入标准。在血液透析患者中，比较 FGF23 分布的下三分之一与上三分之一，全因死亡率的汇总 HR（95%置信区间）为 1.94（1.47，2.56），心血管死亡率为 2.4（1.64，3.51）。对于 OPG 分布的相同基线比较，全因死亡率的汇总 HR 为 1.8（0.95，3.39），心血管死亡率为 2.53（1.29，4.94）。报告的 RANK 配体、OPN、Klotho 蛋白和 BMP-7 的风险估计值不适合进行合并；然而，只有 Klotho 蛋白与死亡率显著相关。对于肾移植受者，确定了四项研究调查 FGF23 和 OPG 与死亡率的关系，所有这些研究都报告了显著的相关性。
在血液透析患者中，FGF23 是全因和心血管死亡率的预测因子，而 OPG 的预测价值仅限于心血管死亡率。需要进一步的研究来深入了解这些生物标志物在肾移植受者中的预后价值。
