University of British Columbia, Vancouver, Canada.
Nephrol Dial Transplant. 2014 May;29(5):1037-47. doi: 10.1093/ndt/gft479. Epub 2013 Dec 26.
Newer biomarkers, reflective of biological processes, such as inflammation and fibrosis, cardiac stretch or damage and vascular health may be useful in understanding clinical events in chronic kidney disease (CKD). We assessed whether these newer biomarkers, alone or as a panel, improve risk prediction for renal replacement therapy or death, over and above conventional clinical, demographic and laboratory variables.
We conducted a prospective observational Canadian cohort study in 2544 CKD patients with estimated glomerular filtration rate (eGFR) of 15-45 mL/min/1.73 m(2), under nephrology care, in urban and rural centers. We measured traditional clinical and laboratory risk factors, as well as newer biomarkers: cystatin C, high sensitivity c-reactive protein (hsCRP), interleukin 6 (IL6), transforming growth factor β1 (TGFβ1), fibroblast growth factor 23 (FGF23), N-terminal probrain natriuretic peptide (NT-proBNP), troponin I and asymmetric dimethylarginine (ADMA). Key outcomes were renal replacement therapy (RRT, dialysis or transplantation) and death, during the first year follow-up after enrollment: a time point important for clinical decision-making for patients and providers.
Newer biomarkers do not improve the prediction of RRT, when added to conventional risk factors such as eGFR, urine albumin to creatinine ratio, hemoglobin, phosphate and albumin. However, in predicting death within 1 year, cystatin C, NT-proBNP, hsCRP and FGF23 values significantly improved model discrimination and reclassification: c statistic increased by absolute 4.3% and Net Reclassification Improvement for categories of low, intermediate and high risk at 11.2%.
Our findings suggest that the addition of newer biomarkers may be useful in predicting death in patients with established CKD within a 1-year timeframe. This information may be useful in informing prognosis and redirect resources to serve patients at higher risk to improve outcomes and sustainability of the nephrology care system.
反映生物过程的新型生物标志物，如炎症和纤维化、心脏拉伸或损伤以及血管健康，可能有助于了解慢性肾脏病（CKD）中的临床事件。我们评估了这些新型生物标志物，无论是单独使用还是作为一组标志物，是否可以改善对肾脏替代治疗或死亡的风险预测，超过了传统的临床、人口统计学和实验室变量。
我们在加拿大进行了一项前瞻性观察性队列研究，纳入了 2544 名接受肾脏科护理的、估算肾小球滤过率（eGFR）为 15-45 mL/min/1.73 m²的 CKD 患者，这些患者来自城市和农村中心。我们测量了传统的临床和实验室危险因素，以及新型生物标志物：胱抑素 C、高敏 C 反应蛋白（hsCRP）、白细胞介素 6（IL6）、转化生长因子β1（TGFβ1）、成纤维细胞生长因子 23（FGF23）、N 末端脑钠肽前体（NT-proBNP）、肌钙蛋白 I 和不对称二甲基精氨酸（ADMA）。主要结局是在登记后 1 年内接受肾脏替代治疗（RRT，透析或移植）和死亡，这是患者和医生进行临床决策的重要时间点。
新型生物标志物不能改善传统危险因素（如 eGFR、尿白蛋白与肌酐比、血红蛋白、磷酸盐和白蛋白）的预测作用，不能改善 RRT 的预测作用。然而，在预测 1 年内死亡方面，胱抑素 C、NT-proBNP、hsCRP 和 FGF23 值显著提高了模型的区分度和重新分类能力：c 统计值增加了绝对 4.3%，11.2%的低、中、高危类别重新分类获益显著。
我们的研究结果表明，在 1 年时间范围内，新型生物标志物的加入可能有助于预测已确诊 CKD 患者的死亡。这些信息可能有助于提供预后信息，并重新分配资源，以服务于高风险患者，改善预后并提高肾脏科护理系统的可持续性。
