循环可溶性 TRAIL 是炎症的负性标志物，与慢性肾脏病患者的死亡风险呈负相关。

The circulating soluble TRAIL is a negative marker for inflammation inversely associated with the mortality risk in chronic kidney disease patients.

机构信息

INSERM ERI-12 (EA 4292), Amiens, France.

出版信息

Nephrol Dial Transplant. 2010 Aug;25(8):2596-602. doi: 10.1093/ndt/gfq042. Epub 2010 Feb 26.

DOI:10.1093/ndt/gfq042

PMID:20190248

Abstract

BACKGROUND

Chronic kidney disease (CKD) is associated with accelerated atherosclerosis and an inadequate inflammatory response which may account for the high morbidity and mortality observed in this population. In vitro and preclinical evidence suggests that the tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) might be involved in both the atherosclerosis pathway and modulation of the inflammatory response. The aim of the present study was thus to (i) determine serum levels of soluble TRAIL (sTRAIL) in a cohort of CKD patients, (ii) assess the relationship between sTRAIL and other inflammatory biomarkers (C-reactive protein and albumin) and (iii) evaluate the association between serum sTRAIL levels and the mortality risk.

METHODS

One hundred and thirty patients (mean +/- SD age: 67 +/- 12; 62% males; 8% at CKD stage 2, 26% at stage 3, 27% at stage 4, 8% at stage 5 and 31% at stage 5D) were assayed for sTRAIL and the selected biochemical parameters and then prospectively monitored for mortality.

RESULTS

CKD stage 5D patients had significantly lower serum sTRAIL levels (median: 46 pg/ml) than patients at CKD stages 2 and 3 (median: 62 pg/ml) or stages 4 and 5 (median: 71 pg/ml). There was no correlation between serum sTRAIL and the estimated glomerular filtration rate (GFR) (r(2) = 0.017, P = 0.22) in pre-dialysis patients. In a multivariate regression analysis, the body mass index (beta = 1.48, P = 0.001) and the serum C-reactive protein (CRP) level (beta = -8.841, P < 0.0001) were independently associated with serum sTRAIL. During follow-up (mean: 772 +/- 286 days), 36 patients died (19 from cardiovascular events, 8 from infectious events and 9 from other causes). The lowest sTRAIL levels (first tertile) were associated with the worst all-cause survival (P = 0.010). Cox regression analyses (with non-cumulative models including age, albumin and CRP as covariates) confirmed the low serum sTRAIL level (first tertile) as an independent predictor of all-cause mortality.

CONCLUSIONS

Circulating sTRAIL is a negative marker for inflammation and is inversely associated with the mortality risk in CKD patients. Further studies are needed to better understand the role of sTRAIL as an inflammatory marker and to confirm its protective role in the CKD population.

摘要

背景

慢性肾脏病（CKD）与动脉粥样硬化加速和炎症反应不足有关，这可能是该人群发病率和死亡率高的原因。体外和临床前证据表明，肿瘤坏死因子相关凋亡诱导配体（TRAIL）可能参与动脉粥样硬化途径和炎症反应的调节。因此，本研究的目的是：（i）确定 CKD 患者队列中的可溶性 TRAIL（sTRAIL）水平，（ii）评估 sTRAIL 与其他炎症生物标志物（C 反应蛋白和白蛋白）之间的关系，（iii）评估血清 sTRAIL 水平与死亡率风险之间的关系。

方法

对 130 名患者（平均年龄 +/- SD：67 +/- 12；62%为男性；8%为 CKD 2 期，26%为 3 期，27%为 4 期，8%为 5 期，31%为 5D 期）进行 sTRAIL 和所选生化参数检测，然后进行前瞻性死亡监测。

结果

CKD 5D 期患者的血清 sTRAIL 水平明显低于 CKD 2 期和 3 期（中位数：62pg/ml）或 4 期和 5 期（中位数：71pg/ml）患者（中位数：46pg/ml）。在未接受透析的患者中，血清 sTRAIL 与估计肾小球滤过率（GFR）之间无相关性（r²=0.017，P=0.22）。在多元回归分析中，体重指数（β=1.48，P=0.001）和血清 C 反应蛋白（CRP）水平（β=-8.841，P<0.0001）与血清 sTRAIL 独立相关。在随访期间（平均：772 +/- 286 天），36 名患者死亡（19 名死于心血管事件，8 名死于感染事件，9 名死于其他原因）。最低的 sTRAIL 水平（第一三分位数）与所有原因的生存最差相关（P=0.010）。Cox 回归分析（包括年龄、白蛋白和 CRP 作为协变量的非累积模型）证实了低血清 sTRAIL 水平（第一三分位数）是全因死亡率的独立预测因子。