Predictive value of composite inflammatory markers combined with T-cell cytokines for the prognosis of sepsis patients complicated with severe acute kidney injury
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摘要: 目的 探讨合并严重急性肾损伤的脓毒症患者外周血复合炎性标志物及血清T细胞因子特征及联合预测患者预后的价值。方法 选取2022年6月—2024年7月在衡水市第二人民医院急诊科收治的合并严重急性肾损伤的脓毒症患者195例作为研究组，另外选择同期治疗的50例脓毒症患者作为单纯脓毒症组、行体检的50例健康人作为对照组。研究组患者根据28 d内是否死亡划分为死亡组(49例)和存活组(146例)。对比不同组患者间一般人口学资料、外周血复合炎性标志物[中性粒细胞/淋巴细胞比值(neutrophil-to-lymphocyte ratio，NLR)、血小板/淋巴细胞比值(platelet-to-lymphocyte ratio，PLR)、系统免疫炎症指数(systemic immune-inflammation index，SII)、全身炎症反应指数(systemic inflammatory response index，SIRI)]及血清T细胞因子[肿瘤坏死因子α(tumor necrosis factor-α，TNF-α)、白细胞介素1(interleukin-1，IL-1)、IL-6、IL-17、IL-35]水平的差异。通过单因素、多因素logistic回归分析评价单因素分析中P＜0.05的指标与合并严重急性肾损伤的脓毒症患者短期死亡的相关性；通过受试者工作特征曲线(receiver operating characteristic curve，ROC)、曲线下面积(area under the curve，AUC)评价各危险因素独立及联合预测合并严重急性肾损伤的脓毒症患者短期死亡的效能；通过校准曲线和决策曲线(decision curve analysis，DCA)评价联合预测模型的拟合度和净收益。结果 研究组患者NLR、PLR、SII、SIRI、TNF-α、IL-1、IL-6、IL-17、IL-35均显著高于单纯脓毒症组和对照组(P＜0.05)，死亡组患者SOFA评分、APACHEⅡ评分、SII、SIRI、IL-1、IL-17、IL-35均显著高于存活组(P＜0.05)；单因素及多因素logistic回归分析提示SII、SIRI、IL-1、IL-17、IL-35均与合并严重急性肾损伤的脓毒症患者短期死亡存在显著相关性(P＜0.05)；ROC曲线分析表明SII、SIRI、IL-1、IL-17、IL-35独立及联合预测合并严重急性肾损伤的脓毒症患者短期死亡风险的AUC均较高(P＜0.05)。Delong检验表明联合预测AUC显著大于SII、SIRI、IL-1、IL-17、IL-35独立预测的AUC(Z=3.664、3.451、4.013、3.448、3.378，P＜0.05)。校准曲线分析表明基于SII、SIRI、IL-1、IL-17、IL-35的联合预测模型拟合度较好(Hosmer-Lemeshow，P=0.481)，DCA分析提示二者联合预测在阈值概率0~0.850均可提供最大净收益。结论 合并严重急性肾损伤的脓毒症患者SII、SIRI、IL-1、IL-17、IL-35水平较高均与短期死亡风险密切相关，基于上述指标的预测模型在辅助判断合并严重急性肾损伤的脓毒症患者短期死亡风险中具有较高价值。Abstract: Objective To explore the characteristics of peripheral blood composite inflammatory markers and serum T-cell cytokines in sepsis patients with severe acute kidney injury, and the value of their combined use in predicting the patients' prognosis.Methods From June 2022 to July 2024, 195 cases of patients with sepsis complicated by severe acute kidney injury admitted to Hengshui Second People's Hospital were selected as the study group. Additionally, 50 cases of patients with sepsis who received treatment during the same period were chosen as the pure sepsis group, and 50 healthy individuals who underwent physical examinations were selected as the control group. Among the patients in the study group, 49 cases belonged to the deceased group while 146 cases were in the survival group, based on their survival status within 28 days. The analysis encompassed the comparison of demographic characteristics, peripheral blood composite inflammatory markers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammatory index (SII), systemic inflammatory response index (SIRI), and serum T-cell factors, such as tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), IL-6, IL-17, IL-35, between different groups. Univariate and multivariate logistic regression analyses were carried out to investigate the association between indicators identified with a significance level of P < 0.05 in the univariate analysis and short-term mortality outcomes in patients with sepsis complicated by severe acute kidney injury. The predictive performance of each risk factor for short-term mortality was evaluated through receiver operating characteristic (ROC) curves and calculation of the area under the curve (AUC). Furthermore, the calibration curves and decision curve analysis (DCA) were utilized to assess the goodness-of-fit and net benefit of the combined prediction model.Results In the study group, the levels of NLR, PLR, SII, SIRI, TNF-α, IL-1, IL-6, IL-17, and IL-35 were found to be significantly elevated compared to those in the pure sepsis group and control group (P < 0.05). It was observed that the deceased group had significantly higher SOFA scores, APACHE Ⅱ scores, SII, SIRI, IL-1, IL-17, and IL-35 compared to the survival group (P < 0.05). Both univariate and multivariate logistic regression analyses showed strong associations between SII, SIRI, IL-1, IL-17, IL-35, and short-term mortality among sepsis patients with severe acute kidney injury (P < 0.05). The ROC curve analysis demonstrated high AUC values for SII, SIRI, IL-1, IL-17, and IL-35 in predicting the risk of short-term mortality in these patients (P < 0.05). Additionally, the combined prediction AUC obtained from the DeLong test was significantly greater than the AUCs of individual predictors (SII, SIRI, IL-1, IL-17, IL-35) (Z=3.664, 3.451, 4.013, 3.448, 3.378, P < 0.05). The calibration curve analysis indicated that the combined prediction model based on SII, SIRI, IL-1, IL-17, and IL-35 was well-fitted (Hosmer-Lemeshow, P=0.481), and the DCA analysis suggested that within a threshold probability range of 0 to 0.850, the combined prediction model provided the maximum net benefit.Conclusion Heightened concentrations of SII, SIRI, IL-1, IL-17, and IL-35 in individuals with sepsis complicated by severe acute kidney injury are strongly linked to the risk of short-term mortality. A predictive model incorporating these biomarkers demonstrated high clinical utility in assessing short-term mortality risk for these patients.
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Key words:
- sepsis /
- acute kidney injury /
- inflammatory markers /
- cytokines /
- mortality risk
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表 1 研究组、单纯脓毒症组和对照组的基本资料比较
X±S 指标 研究组(195例) 单纯脓毒症组(50例) 对照组(50例) F/χ2 P 年龄/岁 58.40±3.45 58.34±3.22 57.94±3.24 0.372 0.690 性别/例(%) 0.309 0.857 男 106(54.4) 25(50.0) 27(54.0) 女 89(45.6) 25(50.0) 23(46.0) BMI/(kg/m2) 23.28±1.31 23.35±1.31 22.94±1.13 1.642 0.195 吸烟史/例(%) 0.037 0.982 有 92(47.2) 23(46.0) 23(46.0) 无 103(52.8) 27(54.0) 27(54.0) 饮酒史/例(%) 0.195 0.907 有 76(39.0) 20(40.0) 18(36.0) 无 119(61.0) 30(60.0) 32(64.0) 基础疾病史/例(%) 1.682 0.947 高血压 40(20.5) 12(24.0) 11(22.0) 糖尿病 33(16.9) 9(18.0) 10(20.0) 冠心病 41(21.1) 10(20.0) 7(14.0) 无 81(41.5) 19(38.0) 22(44.0) 
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表 2 死亡组和存活组的基本资料比较
X±S 指标 死亡组(49例) 存活组(146例) t/χ2 P 年龄/岁 58.59±3.37 58.34±3.48 0.449 0.654 性别/例(%) 0.015 0.904 男 27(55.1) 79(54.1) 女 22(44.9) 67(45.9) BMI/(kg/m2) 23.23±1.47 23.29±1.26 0.249 0.804 吸烟史/例(%) 0.085 0.771 有 24(49.0) 68(46.6) 无 25(51.0) 78(53.4) 饮酒史/例(%) 0.001 0.974 有 19(38.8) 57(39.0) 无 30(61.2) 89(61.0) 基础疾病史/例(%) 1.449 0.484 高血压 18(36.7) 62(46.6) 糖尿病 18(36.7) 46(31.5) 冠心病 13(26.5) 32(21.9) SOFA评分/分 8.88±2.25 8.12±2.16 2.094 0.038 APACHEⅡ/分 23.80±3.07 22.94±2.10 2.187 0.030
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表 3 研究组、单纯脓毒症组和对照组间外周血复合炎性标志物及血清T细胞因子比较
X±S 观察指标 研究组(195例) 单纯脓毒症组(50例) 对照组(50例) F P NLR 11.03±1.67 9.43±1.36 1.80±0.13 782.889 ＜0.001 PLR 286.67±56.40 245.33±46.17 97.80±3.78 277.948 ＜0.001 SII 1 236.40±208.50 1 084.01±151.62 287.35±43.41 543.240 ＜0.001 SIRI 7.17±1.68 6.11±1.39 1.29±0.27 310.967 ＜0.001 TNF-α/(pg/mL) 138.77±21.80 126.46±20.96 10.14±2.05 853.962 ＜0.001 IL-1/(pg/mL) 134.31±20.99 116.20±18.14 9.26±2.13 895.631 ＜0.001 IL-6/(pg/mL) 112.20±15.63 101.00±15.18 13.38±3.03 968.307 ＜0.001 IL-17/(pg/mL) 79.21±16.00 70.13±13.83 7.41±1.34 509.858 ＜0.001 IL-35/(pg/mL) 149.21±24.60 133.51±20.20 10.82±1.95 815.910 ＜0.001
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表 4 死亡组和存活组间外周血复合炎性标志物及血清T细胞因子比较
X±S 指标 死亡组(49例) 存活组(146例) t P NLR 11.12±1.78 11.00±1.64 0.453 0.651 PLR 288.68±64.94 281.99±53.37 0.718 0.474 SII 1307.21±312.51 1212.64±153.53 2.795 0.006 SIRI 7.76±2.19 6.96±1.42 2.944 0.004 TNF-α/(pg/mL) 137.58±24.41 139.17±20.93 0.443 0.658 IL-1/(pg/mL) 141.13±23.63 132.02±19.59 2.671 0.008 IL-6/(pg/mL) 111.12±15.43 112.57±15.73 0.558 0.578 IL-17/(pg/mL) 84.15±16.49 77.55±15.54 2.533 0.012 IL-35/(pg/mL) 157.24±27.15 146.52±23.15 2.682 0.008
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表 5 合并严重急性肾损伤的脓毒症患者短期死亡风险的危险因素单因素logistic回归分析
指标 β SE Wald χ2 P OR(95%CI) SOFA评分 0.160 0.078 2.057 0.040 1.174(1.008~1.367) APACHEⅡ评分 0.149 0.070 2.144 0.032 1.161(1.013~1.330) SII 0.002 0.001 2.700 0.007 1.002(1.001~1.004) SIRI 0.288 0.102 2.825 0.005 1.334(1.092~1.629) IL-1 0.022 0.008 2.587 0.010 1.022(1.005~1.039) IL-17 0.026 0.011 2.466 0.014 1.027(1.005~1.048) IL-35 0.018 0.007 2.597 0.009 1.019(1.005~1.033)
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表 6 合并严重急性肾损伤的脓毒症患者短期死亡风险的危险因素多因素logistic回归分析
指标 β SE Wald χ2 P OR(95%CI) 常量 -18.938 3.441 -5.503 ＜0.001 0 SOFA评分 0.023 0.012 1.924 0.054 1.024(1.000~1.048) APACHEⅡ评分 0.002 0.001 1.725 0.085 1.002(1.000~1.003) SII 0.161 0.079 2.044 0.041 1.175(1.007~1.371) SIRI 0.287 0.118 2.441 0.015 1.333(1.058~1.679) IL-1 0.022 0.009 2.403 0.016 1.022(1.004~1.041) IL-17 0.207 0.090 2.298 0.022 1.230(1.031~1.467) IL-35 0.023 0.008 2.750 0.006 1.023(1.007~1.039)
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表 7 合并严重急性肾损伤的脓毒症患者短期死亡风险的危险因素多因素logistic回归分析
危险因素 AUC SE 95%CI P 截断值 灵敏度/% 特异度/% 约登指数 SII 0.596 0.062 0.474~0.718 0.045 1 458.13 44.90 94.52 0.394 SIRI 0.608 0.056 0.499~0.717 0.024 7.58 65.31 65.07 0.304 IL-1 0.512 0.048 0.418~0.606 0.026 127.23 pg/mL 93.88 17.12 0.110 IL-17 0.612 0.048 0.517~0.707 0.019 87.79 pg/mL 48.98 78.08 0.271 IL-35 0.620 0.050 0.521~0.719 0.012 162.61 pg/mL 51.02 80.14 0.312 联合 0.796 0.041 0.716~0.876 ＜0.001 - 61.22 91.78 0.530
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