Parikh Chirag R, Puthumana Jeremy, Shlipak Michael G, Koyner Jay L, Thiessen-Philbrook Heather, McArthur Eric, Kerr Kathleen, Kavsak Peter, Whitlock Richard P, Garg Amit X, Coca Steven G
Program of Applied Translational Research, Department of Medicine, Yale University School of Medicine, New Haven, Connecticut;
Department of Internal Medicine, Veterans Affairs Medical Center, West Haven, Connecticut.
J Am Soc Nephrol. 2017 Dec;28(12):3699-3707. doi: 10.1681/ASN.2017010055. Epub 2017 Aug 14.
Clinical AKI, measured by serum creatinine elevation, is associated with long-term risks of adverse cardiovascular (CV) events and mortality in patients after cardiac surgery. To evaluate the relative contributions of urine kidney injury biomarkers and plasma cardiac injury biomarkers in adverse events, we conducted a multicenter prospective cohort study of 968 adults undergoing cardiac surgery. On postoperative days 1-3, we measured five urine biomarkers of kidney injury (IL-18, NGAL, KIM-1, L-FABP, and albumin) and five plasma biomarkers of cardiac injury (NT-proBNP, H-FABP, hs-cTnT, cTnI, and CK-MB). The primary outcome was a composite of long-term CV events or death, which was assessed national health care databases. During a median 3.8 years of follow-up, 219 (22.6%) patients experienced the primary outcome (136 CV events and 83 additional deaths). Compared with patients without postsurgical AKI, patients who experienced AKI Network stage 2 or 3 had an adjusted hazard ratio for the primary composite outcome of 3.52 (95% confidence interval, 2.17 to 5.71). However, none of the five urinary kidney injury biomarkers were significantly associated with the primary outcome. In contrast, four out of five postoperative cardiac injury biomarkers (NT-proBNP, H-FABP, hs-cTnT, and cTnI) strongly associated with the primary outcome. Mediation analyses demonstrated that cardiac biomarkers explained 49% (95% confidence interval, 1% to 97%) of the association between AKI and the primary outcome. These results suggest that clinical AKI at the time of cardiac surgery is indicative of concurrent CV stress rather than an independent renal pathway for long-term adverse CV outcomes.
通过血清肌酐升高来衡量的临床急性肾损伤(AKI)与心脏手术后患者发生不良心血管(CV)事件和死亡的长期风险相关。为了评估尿肾损伤生物标志物和血浆心脏损伤生物标志物在不良事件中的相对作用,我们对968例接受心脏手术的成年人进行了一项多中心前瞻性队列研究。在术后第1至3天,我们测量了五种肾损伤尿生物标志物(白细胞介素-18、中性粒细胞明胶酶相关脂质运载蛋白、肾损伤分子-1、肝脏型脂肪酸结合蛋白和白蛋白)和五种心脏损伤血浆生物标志物(N末端B型利钠肽原、心脏型脂肪酸结合蛋白、高敏肌钙蛋白T、肌钙蛋白I和肌酸激酶同工酶)。主要结局是长期CV事件或死亡的复合结局,通过国家医疗保健数据库进行评估。在中位3.8年的随访期间,219例(22.6%)患者出现了主要结局(136例CV事件和83例额外死亡)。与无术后AKI的患者相比,经历急性肾损伤网络(AKI Network)2期或期的患者,其主要复合结局的调整后风险比为3.52(95%置信区间,2.17至5.71)。然而,五种尿肾损伤生物标志物中没有一种与主要结局显著相关。相比之下,五种术后心脏损伤生物标志物中有四种(N末端B型利钠肽原、心脏型脂肪酸结合蛋白、高敏肌钙蛋白T和肌钙蛋白I)与主要结局密切相关。中介分析表明,心脏生物标志物解释了AKI与主要结局之间关联的49%(95%置信区间,1%至97%)。这些结果表明,心脏手术时的临床AKI表明存在并发的CV应激,而非长期不良CV结局的独立肾脏途径。