IL-18联合肾损伤分子-1预测ICU接受CRRT治疗的AKI患者28d病死率

Interleukin-18 combined with kidney injury molecule-1 predict 28-day mortality in patients with acute kidney injury treated with continuous renal replacement therapy in intensive care unit

目的探讨白细胞介素-18(IL-18)联合肾损伤分子-1(KIM-1)对重症医学科(ICU)行连续性肾脏替代治疗(CRRT)的急性肾损伤(AKI)患者28 d病死率的预测价值,并寻找CRRT的启动时机.方法采用前瞻性观察性研究方法,选择2017年6月至2018年2月河北医科大学第四医院ICU收治的行CRRT的AKI危重症患者,并根据改善全球肾脏病预后组织(KDIGO)指南定义分为AKI 2期组和AKI 3期组.记录所有入选患者的基本生命体征,机械通气患者的呼吸机参数.行CRRT前留取尿标本,采用酶联免疫吸附试验(ELISA)检测IL-18和KIM-1水平.电话随访患者28 d生存情况;绘制受试者工作特征曲线(ROC),评估尿IL-18和KIM-1对预后的预测价值.结果研究期间共收治38例患者,排除ICU住院时间<3 d、慢性梗阻性肾脏疾病、腹腔内高压、留取尿标本前4 h内曾应用利尿剂、留取尿标本前已进行肾脏替代治疗患者,最终纳入30例,其中AKI 2期12例,AKI 3期18例.AKI 2期与AKI 3期两组患者间性别、年龄、身高、体重、基本生命体征、基础肾功能及病情严重程度等基础医学特征比较差异均无统计学意义.与AKI 2期组相比,AKI 3期组患者尿KIM-1水平明显升高〔ng/L :6 195.6(5 892.6,7 935.4)比5 487.5(4 769.8,6 353.4),P<0.01〕,但尿IL-18水平差异无统计学意义〔ng/L :52.1(48.1,62.6)比53.9(52.0,57.2),P>0.05〕.所有入选患者均完成28 d随访,AKI 2期组患者28 d全因病死率较AKI 3期组显著降低〔16.7%(2/12)比66.7%(12/18),P<0.05〕.ROC曲线分析显示,尿IL-18对行CRRT的AKI危重症患者28 d病死率的预测价值较小,KIM-1有一定预测价值,以二者联合预测价值更大,ROC曲线下面积(AUC)为0.786〔95%可信区间(95%CI)=0.598~0.914, P=0.001〕,其敏感度为50.0%,特异度为100%.结论尿IL-18联合KIM-1对AKI危重症患者预后有较高的预测价值;对于AKI危重症患者,AKI 2期时启动CRRT治疗较AKI 3期启动可显著降低28 d病死率.

Objective To investigate the predict value of interleukin-18 (IL-18) combine with kidney injury molecule-1 (KIM-1) on 28-day mortality in patients with acute kidney injury (AKI) undergoing continuous renal replacement therapy (CRRT) in intensive care unit (ICU), and to look for the start time of CRRT. Methods A prospective observational study was conducted. The consecutive AKI critical patients who underwent CRRT from June 2017 to February 2018 admitted to ICU of the Fourth Hospital of Hebei Medical University were enrolled. Patients were divided into AKI 2 stage and AKI 3 stage groups according to the guidelines for Kidney Disease: Improving Global Outcomes (KDIGO). Basic vital signs were recorded for all enrolled patients, and ventilator parameters were recorded for patients on ventilation. Urine specimens were collected before CRRT, and IL-18 and KIM-1 levels were measured by enzyme-linked immunosorbent assay (ELISA). The patients were followed up for 28 days. The receiver operating characteristic (ROC) curve was drawn to evaluate the predictive value of urinary IL-18 and KIM-1 for prognosis. Results During the study period, 38 patients were treated. The patients with ICU stayed for less than 3 days, chronic obstructive kidney disease, intra-abdominal hypertension (IAH), diuretics usage within 4 hours or renal replacement therapy before urine collection were excluded. Finally, 30 patients were enrolled, including 12 patients with AKI phase 2 and 18 patients with AKI phase 3. There was no significant difference in basic medical characteristics such as gender, age, height, weight, basic vital signs, basic renal function, or severity of disease between AKI 2 stage and AKI 3 stage groups. Compared with the AKI 2 stage group, the level of urine KIM-1 in the AKI 3 stage group was significantly increased [ng/L: 6195.6 (5892.6, 7935.4) vs. 5487.5 (4769.8, 6353.4), P < 0.01], but urine IL-18 level was not statistically significant [ng/L: 52.1 (48.1, 62.6) vs. 53.9 (52.0, 57.2), P > 0.05]. All patients were followed up for 28 days. The 28-day all-cause mortality rate of AKI 2 stage group was significantly lower than that of AKI 3 stage group [16.7%(2/12) vs. 66.7%(12/18), P < 0.05]. ROC curve analysis showed that urinary IL-18 had a small predictive value for the 28-day mortality of AKI patients undergoing CRRT, and KIM-1 had a certain predictive value, and the combined value of the combined detection was greater, and the area under ROC curve (AUC) was 0.786 [95% confidence interval (95%CI)= 0.598-0.914, P = 0.001] with a sensitivity of 50.0% and a specificity of 100%. Conclusions Urine IL-18 combined with urine KIM-1 has a high predictive value for the prognosis of patients with AKI. For critically ill patients with AKI, initiation of CRRT treatment in AKI 2 stage can significantly reduce the 28-day mortality as compared with that in AKI 3 stage.