Alderson Helen V, Ritchie James P, Middleton Rachel, Larsson Anders, Larsson Tobias E, Kalra Philip A
Vascular Research Group, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK.
Salford Royal NHS Foundation Trust, Salford, UK.
Nephrology (Carlton). 2016 Jul;21(7):566-73. doi: 10.1111/nep.12664.
Numerous biomarkers have been shown to associate with clinical endpoints in chronic kidney disease (CKD). There is limited evidence whether biomarkers improve risk prediction in relation to clinical outcomes. Our study investigates whether a small suite of key chronic kidney disease-mineral and bone disorder biomarkers could be used to enhance risk assessment in CKD.
Fetuin-A, fibroblast growth factor-23 and osteoprotegerin were measured on baseline plasma samples from 463 patients recruited to the Chronic Renal Insufficiency Standards Implementation Study. The biomarkers were analysed in relation to progression to end stage kidney disease, death and major cardiovascular events.
Over a median follow up of 46 months (interquartile range 21-69), fibroblast growth factor-23 was associated with risk for renal replacement therapy (hazard ratio (HR) 1.35, P = 0.05, 95% confidence interval (CI) 1.001-1.820), cardiovascular events (HR 1.74 P < 0.001, 95% CI 1.303-1.305) and death (HR 1.4 P = 0.005, 95% CI 1.109-1.767). Osteoprotegerin was associated with risk for death (HR 1.06, P = 0.03, 95% CI 1.006-1.117). There was no clear association between Fetuin-A and any of the clinical endpoints. The addition of biomarkers to risk models led to marginal improvement in model discrimination and reclassification.
Biomarkers are often associated with clinical endpoints, and we observed such associations in our study of patients with advanced CKD. However, the markers analysed in our study were of limited benefit in improving the prediction of these outcomes. Any extra information biomarkers may provide to improve risk prediction in clinical practice needs to be carefully balanced against the potential cost of these tools.
众多生物标志物已被证明与慢性肾脏病（CKD）的临床终点相关。关于生物标志物是否能改善与临床结局相关的风险预测，证据有限。我们的研究调查了一小套关键的慢性肾脏病 - 矿物质和骨代谢紊乱生物标志物是否可用于加强CKD的风险评估。
在纳入慢性肾功能不全标准实施研究的463例患者的基线血浆样本中检测胎球蛋白 - A、成纤维细胞生长因子 - 23和骨保护素。分析这些生物标志物与进展至终末期肾病、死亡和主要心血管事件的关系。
在中位随访46个月（四分位间距21 - 69个月）期间，成纤维细胞生长因子 - 23与肾脏替代治疗风险相关（风险比（HR）1.35，P = 0.05，95%置信区间（CI）1.001 - 1.820）、心血管事件（HR 1.74，P < 0.001，95% CI 1.303 - 1.305）和死亡（HR 1.4，P = 0.005，95% CI 1.109 - 1.767）。骨保护素与死亡风险相关（HR 1.06，P = 0.03，95% CI 1.006 - 1.117）。胎球蛋白 - A与任何临床终点之间均无明确关联。将生物标志物添加到风险模型中导致模型辨别力和重新分类有边际改善。
生物标志物通常与临床终点相关，我们在晚期CKD患者的研究中观察到了此类关联。然而，我们研究中分析的标志物在改善这些结局的预测方面益处有限。生物标志物在临床实践中为改善风险预测可能提供的任何额外信息都需要与这些工具的潜在成本仔细权衡。
