Weiss Raphael, Meersch Melanie, Gerke Mena, Wempe Carola, Schäfers Michael, Kellum John A, Zarbock Alexander
From the Departments of Anesthesiology, Intensive Care and Pain Medicine.
Nuclear Medicine, University Hospital Münster, Münster, Germany.
Anesth Analg. 2023 Nov 1;137(5):1029-1038. doi: 10.1213/ANE.0000000000006288. Epub 2022 Nov 29.
Acute kidney injury (AKI) is a common complication after cardiac surgery and is associated with increased morbidity and mortality. However, no specific treatment options are available, emphasizing the need for preventive measures. The aim of this study was to clarify the effect of glutamine on [TIMP2]*[IGFBP7] levels at the end of the intervention period.
In a randomized clinical, double-blind pilot study, 64 eligible cardiac surgery patients at high risk for AKI identified by high urinary [TIMP2][IGFBP7] were randomized, and body weight-adapted intravenous glutamine or saline-control was administered continuously for 12 hours postoperatively. The primary outcome was urinary [TIMP2][IGFBP7] at the end of the 12-hour study period. Secondary outcomes included kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) at 12 hours, overall AKI rates at 72 hours, free days through day 28 of mechanical ventilation and vasoactive medication, renal recovery at day 90, requirement of renal replacement therapy and mortality each at days 30, 60, and 90, length of intensive care unit (ICU) and hospital stay, and major adverse kidney events consisting of mortality, dialysis dependency, and persistent renal dysfunction (serum creatinine ≥2× compared to baseline value) at day 90 (major adverse kidney event; MAKE 90 ).
Sixty-four patients (mean age, 68.38 [standard deviation {SD} ± 10.48] years; 10 of 64 women) were enrolled and randomized. Patients received coronary artery bypass graft surgery (32/64), valve surgery (18/64), coronary artery bypass graft and valve surgery (6/64), or other procedures (8/64). Mean on-pump time was 68.38 (standard deviation ± 10.48) minutes. After glutamine administration, urinary [TIMP-2]*[IGFBP7] was significantly lower in the glutamine compared to the control group (primary end point, intervention: median, 0.18 [Q1, Q3; 0.09, 0.29], controls: median, 0.44 [Q1, Q3; 0.14, 0.79]; P = .01). In addition, [KIM-1] and [NGAL] were also significantly lower in the glutamine group. The overall AKI rate within 72 hours was not different among groups: (intervention 11/31 [35.5%] versus control 8/32 [25.0%]; P = .419; relative risk [RR], 0.86% [95% confidence interval {CI}, 0.62-1.20]). There were no differences regarding secondary end points.
Glutamine significantly decreased markers of kidney damage in cardiac surgery patients at high risk for AKI. Future trials have to be performed to investigate whether the administration of glutamine might be able to reduce the occurrence of AKI after cardiac surgery.
急性肾损伤（AKI）是心脏手术后常见的并发症，与发病率和死亡率增加相关。然而，目前尚无特定的治疗方案，因此强调预防措施的必要性。本研究的目的是阐明谷氨酰胺对干预期末[TIMP2]*[IGFBP7]水平的影响。
在一项随机临床双盲试验性研究中，64例经高尿[TIMP2][IGFBP7]确定为AKI高危的符合条件的心脏手术患者被随机分组，术后持续12小时静脉输注根据体重调整剂量的谷氨酰胺或生理盐水作为对照。主要结局指标是12小时研究期末的尿[TIMP2][IGFBP7]。次要结局指标包括12小时时的肾损伤分子-1（KIM-1）和中性粒细胞明胶酶相关脂质运载蛋白（NGAL）、72小时时的总体AKI发生率、机械通气和血管活性药物使用至第28天的无使用天数、第90天时的肾功能恢复情况、第30天、60天和90天时肾脏替代治疗的需求和死亡率、重症监护病房（ICU）住院时间和总住院时间，以及第90天时由死亡率、透析依赖和持续性肾功能不全（血清肌酐较基线值升高≥2倍）组成的主要不良肾脏事件（MAKE 90）。
64例患者（平均年龄68.38[标准差{SD}±10.48]岁；64例中有10例女性）入组并随机分组。患者接受冠状动脉搭桥手术（32/64）、瓣膜手术（18/64）、冠状动脉搭桥和瓣膜手术（6/64）或其他手术（8/64）。平均体外循环时间为68.38（标准差±10.48）分钟。给予谷氨酰胺后，谷氨酰胺组的尿[TIMP-2]*[IGFBP7]显著低于对照组（主要终点，干预组：中位数0.18[四分位数间距{IQR}；0.09，0.29]，对照组：中位数0.44[IQR；0.14，0.79]；P = 0.01）。此外，谷氨酰胺组的[KIM-1]和[NGAL]也显著降低。72小时内的总体AKI发生率在各组间无差异：（干预组11/31[35.5%]与对照组8/32[25.0%]；P = 0.419；相对危险度[RR]，0.86%[95%置信区间{CI}，0.62 - 1.20]）。次要终点方面无差异。
谷氨酰胺显著降低了AKI高危心脏手术患者的肾损伤标志物水平。未来必须开展试验，以研究给予谷氨酰胺是否能够降低心脏手术后AKI的发生率。
