The circulating soluble TRAIL is a negative marker for inflammation inversely associated with the mortality risk in chronic kidney disease patients
The circulating soluble TRAIL is a negative marker for inflammation inversely associated with the mortality risk in chronic kidney disease patients
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DOI：
10.1093/ndt/gfq042
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发表时间：
2010-08-01
影响因子：
6.1
通讯作者：
Massy, Ziad A.
中科院分区：
文献类型：
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作者：
Liabeuf, Sophie;Barreto, Daniela V.;Massy, Ziad A.
背景慢性肾脏疾病（CKD）与动脉粥样硬化加速和炎症反应不足相关，这可能是该人群中观察到的高发病率和死亡率的原因。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制。因此，本研究的目的是（i）确定CKD患者队列中可溶性TRAIL（sTRAIL）的血清水平，（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，以及（iii）评估血清sTRAIL水平与死亡风险之间的关联。对130名患者（平均+/- SD年龄：67 +/- 12岁; 62%为男性; 8%为CKD 2期，26%为3期，27%为4期，8%为5期，31%为SD期）进行了sTRAIL和选定的生化参数检测，然后前瞻性监测死亡率。结果。CKD SD期患者的血清sTRAIL水平（中位数：46 pg/ml）显著低于CKD 2期和3期（中位数：62 pg/ml）或4期和5期（中位数：71 pg/ml）患者。透析前患者血清sTRAIL水平与肾小球滤过率（GFR）无相关性（r（2）= 0.017，P = 0.22）。多因素回归分析显示，体重指数（β = 1.48，P = 0.001）和血清C反应蛋白（β =-8.841，P < 0.0001）与血清sTRAIL水平独立相关。在随访期间（平均：772 ± 286天），36例患者死亡（19例死于心血管事件，8例死于感染事件，9例死于其他原因）。最低sTRAIL水平（第一个三分位数）与最差全因生存率相关（P = 0.010）。考克斯回归分析（非累积模型包括年龄、白蛋白和CRP作为协变量）证实低血清sTRAIL水平（第一个三分位数）是全因死亡率的独立预测因子。循环sTRAIL是炎症的阴性标志物，与CKD患者的死亡风险呈负相关。需要进一步的研究来更好地了解sTRAIL作为炎症标志物的作用，并确认其在CKD人群中的保护作用。
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 SD) were assayed for sTRAIL and the selected biochemical parameters and then prospectively monitored for mortality.Results. CKD stage SD 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.