Coca Steven G, Garg Amit X, Thiessen-Philbrook Heather, Koyner Jay L, Patel Uptal D, Krumholz Harlan M, Shlipak Michael G, Parikh Chirag R
Section of Nephrology, Yale University School of Medicine, Program of Applied Translational Research, Veterans Affairs Connecticut Healthcare System, New Haven, Connecticut;
Division of Nephrology, Department of Medicine, Western University, London, Ontario, Canada;
J Am Soc Nephrol. 2014 May;25(5):1063-71. doi: 10.1681/ASN.2013070742. Epub 2013 Dec 19.
Urinary biomarkers of AKI provide prognostic value for in-hospital outcomes, but little is known about their association with longer-term mortality after surgery. We sought to assess the association between kidney injury biomarkers and all-cause mortality in an international, multicenter, prospective long-term follow-up study from six clinical centers in the United States and Canada composed of 1199 adults who underwent cardiac surgery between 2007 and 2009 and were enrolled in the Translational Research in Biomarker Endpoints in AKI cohort. On postoperative days 1-3, we measured the following five urinary biomarkers: neutrophil gelatinase-associated lipocalin, IL-18, kidney injury molecule-1 (KIM-1), liver fatty acid binding protein, and albumin. During a median follow-up of 3.0 years (interquartile range, 2.2-3.6 years), 139 participants died (55 deaths per 1000 person-years). Among patients with clinical AKI, the highest tertiles of peak urinary neutrophil gelatinase-associated lipocalin, IL-18, KIM-1, liver fatty acid binding protein, and albumin associated independently with a 2.0- to 3.2-fold increased risk for mortality compared with the lowest tertiles. In patients without clinical AKI, the highest tertiles of peak IL-18 and KIM-1 also associated independently with long-term mortality (adjusted hazard ratios [95% confidence intervals] of 1.2 [1.0 to 1.5] and 1.8 [1.4 to 2.3] for IL-18 and KIM-1, respectively), and yielded continuous net reclassification improvements of 0.26 and 0.37, respectively, for the prediction of 3-year mortality. In conclusion, urinary biomarkers of kidney injury, particularly IL-18 and KIM-1, in the immediate postoperative period provide additional prognostic information for 3-year mortality risk in patients with and without clinical AKI.
急性肾损伤(AKI)的尿液生物标志物可为住院结局提供预后价值,但对于它们与术后长期死亡率之间的关联却知之甚少。我们试图在一项国际多中心前瞻性长期随访研究中评估肾脏损伤生物标志物与全因死亡率之间的关联,该研究来自美国和加拿大的六个临床中心,共有1199名在2007年至2009年间接受心脏手术且被纳入AKI队列生物标志物终点转化研究的成年人。在术后第1至3天,我们测量了以下五种尿液生物标志物:中性粒细胞明胶酶相关脂质运载蛋白、白细胞介素-18、肾损伤分子-1(KIM-1)、肝脏脂肪酸结合蛋白和白蛋白。在中位随访3.0年(四分位间距为2.2至3.6年)期间,139名参与者死亡(每1000人年55例死亡)。在临床AKI患者中,与最低三分位数相比,尿中性粒细胞明胶酶相关脂质运载蛋白、白细胞介素-18、KIM-1、肝脏脂肪酸结合蛋白和白蛋白峰值的最高三分位数与死亡风险独立相关,增加2.0至3.2倍。在无临床AKI的患者中,白细胞介素-18和KIM-1峰值的最高三分位数也与长期死亡率独立相关(白细胞介素-18和KIM-1的调整后风险比[95%置信区间]分别为1.2[1.0至1.5]和1.8[1.4至2.3]),并且在预测3年死亡率方面,连续净重新分类改善分别为0.26和0.37。总之,术后即刻的肾脏损伤尿液生物标志物,尤其是白细胞介素-18和KIM-1,可为有或无临床AKI的患者提供3年死亡风险的额外预后信息。