Zhang William R, Garg Amit X, Coca Steven G, Devereaux Philip J, Eikelboom John, Kavsak Peter, McArthur Eric, Thiessen-Philbrook Heather, Shortt Colleen, Shlipak Michael, Whitlock Richard, Parikh Chirag R
Program of Applied Translational Research, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut;
Division of Nephrology, Department of Medicine, Western University, London, Ontario, Canada; Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada;
J Am Soc Nephrol. 2015 Dec;26(12):3123-32. doi: 10.1681/ASN.2014080764. Epub 2015 Apr 8.
Inflammation has an integral role in the pathophysiology of AKI. We investigated the associations of two biomarkers of inflammation, plasma IL-6 and IL-10, with AKI and mortality in adults undergoing cardiac surgery. Patients were enrolled at six academic centers (n = 960). AKI was defined as a ≥ 50% or ≥ 0.3-mg/dl increase in serum creatinine from baseline. Pre- and postoperative IL-6 and IL-10 concentrations were categorized into tertiles and evaluated for associations with outcomes of in-hospital AKI or postdischarge all-cause mortality at a median of 3 years after surgery. Preoperative concentrations of IL-6 and IL-10 were not significantly associated with AKI or mortality. Elevated first postoperative IL-6 concentration was significantly associated with higher risk of AKI, and the risk increased in a dose-dependent manner (second tertile adjusted odds ratio [OR], 1.61 [95% confidence interval (95% CI), 1.10 to 2.36]; third tertile adjusted OR, 2.13 [95% CI, 1.45 to 3.13]). First postoperative IL-6 concentration was not associated with risk of mortality; however, the second tertile of peak IL-6 concentration was significantly associated with lower risk of mortality (adjusted hazard ratio, 0.75 [95% CI, 0.57 to 0.99]). Elevated first postoperative IL-10 concentration was significantly associated with higher risk of AKI (adjusted OR, 1.57 [95% CI, 1.04 to 2.38]) and lower risk of mortality (adjusted HR, 0.72 [95% CI, 0.56 to 0.93]). There was a significant interaction between the concentration of neutrophil gelatinase-associated lipocalin, an established AKI biomarker, and the association of IL-10 concentration with mortality (P = 0.01). These findings suggest plasma IL-6 and IL-10 may serve as biomarkers for perioperative outcomes.
炎症在急性肾损伤（AKI）的病理生理学中起着不可或缺的作用。我们研究了两种炎症生物标志物——血浆白细胞介素-6（IL-6）和白细胞介素-10（IL-10）——与接受心脏手术的成年人发生AKI及死亡率之间的关联。研究在六个学术中心招募了患者（n = 960）。AKI被定义为血清肌酐较基线水平升高≥50%或≥0.3 mg/dl。术前和术后IL-6及IL-10浓度被分为三分位数，并评估其与术后中位3年时院内发生AKI或出院后全因死亡率结局之间的关联。术前IL-6和IL-10浓度与AKI或死亡率无显著关联。术后首次IL-6浓度升高与AKI风险显著相关，且风险呈剂量依赖性增加（第二三分位数校正比值比[OR]为1.61[95%置信区间（95%CI）为1.10至2.36]；第三三分位数校正OR为2.13[95%CI为1.45至3.13]）。术后首次IL-6浓度与死亡风险无关；然而，IL-6浓度峰值的第二三分位数与较低的死亡风险显著相关（校正风险比为0.75[95%CI为0.57至0.99]）。术后首次IL-10浓度升高与AKI风险显著相关（校正OR为1.57[95%CI为1.04至2.38]），与死亡风险较低相关（校正风险比为0.72[95%CI为0.56至0.93]）。已确定的AKI生物标志物中性粒细胞明胶酶相关脂质运载蛋白的浓度与IL-10浓度和死亡率之间的关联存在显著交互作用（P = 0.01）。这些发现表明血浆IL-6和IL-10可能作为围手术期结局的生物标志物。
