Zhu Lili, Shi Dongwu
Department of Critical Care Medicine, Shanxi People's Hospital, Taiyuan 030012, Shanxi, China. Corresponding author: Shi Dongwu, Email:
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2016 Aug;28(8):718-22. doi: 10.3760/cma.j.issn.2095-4352.2016.08.010.
OBJECTIVE: To evaluate the early diagnosis value of blood neutrophil gelatinase-associated lipocalin (NGAL) and interleukin-18 (IL-18) in patients with sepsis-induced acute kidney injury (AKI). METHODS: A prospective case controlled study was conducted. Fifty-six patients with sepsis but without renal disease admitted to intensive care unit (ICU) of Shanxi People's Hospital from April 2014 to April 2015 were enrolled. Blood lactic acid and acute physiology and chronic health evaluation II (APACHE II) score at ICU admission were recorded. The urine output, blood urea nitrogen (BUN), serum creatinine (SCr), NGAL, IL-18 and tumor necrosis factor-α (TNF-α) were continuously monitored for 48 hours. The patients were divided into AKI group and non-AKI group according to the diagnostic criteria of Kidney Disease: Improving Global Outcomes (KDIGO). The changes trend in above parameters between the two groups at different time points were compared. The early diagnostic value of NGAL, IL-18, and SCr for sepsis-induced AKI was evaluated by receiver operating characteristic curve (ROC). RESULTS: Compared with non-AKI group, with the time prolongation after ICU admission, the traditional parameters reflecting AKI urine output in sepsis-induced AKI group was decreased gradually, BUN and SCr were gradually increased, and a statistically significant difference was found at 12 hours between the two groups [BUN (mmol/L): 11.8±3.5 vs. 8.2±3.5, SCr (μmol/L): 88.6±11.3 vs. 74.0±11.0, both P < 0.01]; but the new indicators NGAL and IL-18 reflecting AKI had a statistically significant difference at 6 hours [NGAL (μg/L): 426.7±90.7 vs. 382.3±67.9, IL-18 (ng/L): 75.7±9.3 vs. 70.9±7.3, both P < 0.05]. It was shown that in AKI group, NGAL and IL-18 compared with BUN and SCr increased at least 6 hours ahead of schedule. The area under ROC curve (AUC) of 6-hour NGAL and IL-18 in patients with sepsis-induced AKI were 0.821 [95% confidence interval (95%CI) = 0.713-0.931] and 0.719 (95%CI = 0.584-0.853) respectively, superior to SCr (AUC = 0.677, 95%CI = 0.528-0.825). The cutoff value of NGAL was 363.58 μg/L, and the sensitivity and specificity were 88.0% and 86.7% respectively. CONCLUSIONS: NGAL and IL-18 in the early prediction of sepsis patients with AKI are better than SCr, and NGAL was most sensitive. Therefore, NGAL can be used as an early biomarker for the diagnosis of AKI in patients with sepsis.
目的：评估血中性粒细胞明胶酶相关脂质运载蛋白（NGAL）和白细胞介素-18（IL-18）在脓毒症诱导的急性肾损伤（AKI）患者中的早期诊断价值。 方法：进行一项前瞻性病例对照研究。纳入2014年4月至2015年4月期间入住山西省人民医院重症监护病房（ICU）的56例患有脓毒症但无肾脏疾病的患者。记录入住ICU时的血乳酸和急性生理与慢性健康状况评分II（APACHE II）。连续48小时监测尿量、血尿素氮（BUN）、血清肌酐（SCr）、NGAL、IL-18和肿瘤坏死因子-α（TNF-α）。根据改善全球肾脏病预后组织（KDIGO）的诊断标准将患者分为AKI组和非AKI组。比较两组在不同时间点上述参数的变化趋势。通过受试者工作特征曲线（ROC）评估NGAL、IL-18和SCr对脓毒症诱导的AKI的早期诊断价值。 结果：与非AKI组相比，脓毒症诱导的AKI组入住ICU后随着时间延长，反映AKI的传统参数尿量逐渐减少，BUN和SCr逐渐升高，两组在12小时时有统计学显著差异[BUN（mmol/L）：11.8±3.5对8.2±3.5，SCr（μmol/L）：88.6±11.3对74.0±11.0，均P<0.01]；但反映AKI的新指标NGAL和IL-18在6小时时有统计学显著差异[NGAL（μg/L）：426.7±90.7对382.3±67.9，IL-18（ng/L）：75.7±9.3对70.9±7.3，均P<0.05]。结果表明，在AKI组中，NGAL和IL-18较BUN和SCr至少提前6小时升高。脓毒症诱导的AKI患者中6小时NGAL和IL-18的ROC曲线下面积（AUC）分别为0.821[95%置信区间（95%CI）=0.713-0.931]和0.719（95%CI=0.584-0.853），优于SCr（AUC=0.677，95%CI=0.528-0.825）。NGAL的截断值为363.58μg/L，敏感性和特异性分别为88.0%和86.7%。 结论：NGAL和IL-18在脓毒症患者AKI的早期预测方面优于SCr，且NGAL最敏感。因此，NGAL可作为脓毒症患者AKI诊断的早期生物标志物。
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