生物标志物谱、慢性肾脏病病因与死亡率之间的关联
The Association between Biomarker Profiles, Etiology of Chronic Kidney Disease, and Mortality.
作者信息
Langsford David, Tang Mila, Cheikh Hassan Hicham I, Djurdjev Ognjenka, Sood Manish M, Levin Adeera
机构信息
Division of Nephrology, University of British Columbia, Vancouver, Canada.
出版信息
Am J Nephrol. 2017;45(3):226-234. doi: 10.1159/000454991. Epub 2017 Feb 2.
BACKGROUND
Prognosis in chronic kidney disease (CKD) for adverse outcomes differs substantially based on the etiology of CKD. We examined whether the biomarker profile differed based on CKD etiology and whether they were associated with mortality.
METHODS
Prospective observational study of 1,157 patients, 663 with diabetic kidney disease (DKD), 273 with glomerulonephritis (GN), and 221 with cystic/interstitial disease (polycystic kidney disease, pyelonephritis or chronic tubulointerstitial nephritis [PCK/TIN]) were identified in the Canadian Study of Prediction of Dialysis, Death and Interim Cardiovascular events over Time cohort. The outcome of interest was mortality before commencing dialysis. The biomarker profile consisted of N-terminal pro-brain natriuretic peptide (NT-proBNP), troponin I (TnI), asymmetric dimethylarginine (ADMA), interleukin (IL)-6, high sensitivity C-reactive protein, fibroblast growth factor-23 (FGF23), transforming growth factor-beta, 25-hydroxylvitamin D, and cystatin C (CysC).
RESULTS
The mean estimated glomerular filtration rate was 27 mL/min/1.73 m2 and median follow-up time was 44 months. Mortality before dialysis commencement was the greatest in DKD (20%), followed by PCK/TIN (13%), and was least in those GN (8%). The majority of deaths were cardiovascular in nature, 17, 9, and 5.5% for DKD, PCK/TIN, GN, respectively. Those with DKD had higher hazard for mortality, unadjusted (hazard ratio [HR] 2.7, 95% CI 1.7-4.3) and adjusted (HR 1.7, 95% CI 1.1-2.8). The biomarker profiles associated with mortality differed significantly by CKD etiology as follows: DKD was associated with CysC (HR 1.3, 95% CI 1.0-1.6), ADMA (HR 1.3, 95% CI 1.1-1.6), and NT-proBNP (HR 1.7, 95% CI 1.4-2.1), GN was associated with FGF23 (HR 1.8, 95% CI 1.1-2.8), TnI (HR 3.6, 95% CI 1.3-9.5), and transforming growth factor-beta (HR 0.6, 95% CI 0.4-0.9) and PCK/TIN was associated with ADMA (HR 1.5, 95% CI 1.3-1.8) and IL-6 (HR 2.1, 95% CI 1.5-3.1).
CONCLUSIONS
Biomarkers profiles differ according to the etiology of CKD and are associated with mortality.
背景
慢性肾脏病（CKD）不良结局的预后因CKD病因不同而有显著差异。我们研究了生物标志物谱是否因CKD病因不同而存在差异，以及它们是否与死亡率相关。
方法
在加拿大透析、死亡及心血管事件长期预测队列研究中，对1157例患者进行了前瞻性观察研究，其中663例为糖尿病肾病（DKD）患者，273例为肾小球肾炎（GN）患者，221例为囊性/间质性疾病（多囊肾病、肾盂肾炎或慢性肾小管间质性肾炎[PCK/TIN]）患者。感兴趣的结局是开始透析前的死亡率。生物标志物谱包括N末端脑钠肽前体（NT-proBNP）、肌钙蛋白I（TnI）、不对称二甲基精氨酸（ADMA）、白细胞介素（IL）-6、高敏C反应蛋白、成纤维细胞生长因子-23（FGF23）、转化生长因子-β、25-羟基维生素D和胱抑素C（CysC）。
结果
平均估算肾小球滤过率为27 mL/min/1.73 m²，中位随访时间为44个月。透析开始前的死亡率在DKD患者中最高（20%），其次是PCK/TIN患者（13%），在GN患者中最低（8%）。大多数死亡为心血管原因，DKD、PCK/TIN、GN患者分别为17%、9%和5.5%。DKD患者的死亡风险更高，未调整时（风险比[HR] 2.7，95%置信区间1.7 - 4.3），调整后（HR 1.7，95%置信区间1.1 - 2.8）。与死亡率相关的生物标志物谱因CKD病因不同而有显著差异，如下：DKD与CysC（HR 1.3，95%置信区间1.0 - 1.6）、ADMA（HR 1.3，95%置信区间1.1 - 1.6）和NT-proBNP（HR 1.7，95%置信区间1.4 - 2.1）相关；GN与FGF23（HR 1.8，95%置信区间1.1 - 2.8）、TnI（HR 3.6，95%置信区间1.3 - 9.5）和转化生长因子-β（HR 0.6，95%置信区间0.4 - 0.9）相关；PCK/TIN与ADMA（HR 1.5，95%置信区间1.3 - 1.8）和IL-6（HR 2.1，95%置信区间1.5 - 3.1）相关。
结论
生物标志物谱因CKD病因不同而存在差异，并与死亡率相关。
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