Diagnostic value of TLR4 and NGAL and uKIM-1 in patients with sepsis complicated with acute kidney injury
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摘要: 目的 分析Toll样受体4(toll like receptor 4，TLR4)、中性粒细胞明胶酶相关脂质运载蛋白(neutrophil gelatinase-associated lipocalin，NGAL)、尿液肾损伤分子-1(urinary kidney injury molecules-1，uKIM-1)在脓毒症患者并发急性肾损伤(acute kidney injury，AKI)中的诊断价值。 方法 选取简阳市人民医院2020年10月—2023年2月收治的脓毒症患者181例。根据是否发生AKI分为AKI组83例(AKIⅠ期30例、AKIⅡ期38例、AKIⅢ期15例)、非AKI组98例。比较AKI组、非AKI组的TLR4、NGAL、uKIM-1水平。采用单因素、多因素logistic回归分析影响脓毒症患者并发AKI的危险因素。对比不同AKI分期的血肌酐(serum creatinine, Scr)、肾小球滤过率(eGFR)、降钙素原、尿量、SOFA评分、TLR4、NGAL、uKIM-1水平。采用Pearson分析TLR4、NGAL、uKIM-1水平与Scr、eGFR、降钙素原、尿量、SOFA评分的相关性。绘制ROC曲线分析TLR4、NGAL、uKIM-1单一及联合检测脓毒症患者并发AKI的诊断价值。 结果 AKI组TLR4、NGAL、uKIM1、降钙素原水平及SOFA评分高于非AKI组，尿量低于非AKI组，差异有统计学意义(P＜0.05)；两组Scr、eGFR比较，差异无统计学意义(P>0.05)。logistic回归结果显示：降钙素原、尿量、TLR4、NGAL、uKIM-1水平上升是影响脓毒症患者并发AKI的危险因素(P＜0.05)。3组间Scr、eGFR比较，差异无统计学意义(P>0.05)；AKI Ⅲ期降钙素原、尿量、SOFA评分、TLR4、NGAL、uKIM-1水平均高于AKI Ⅰ期、AKI Ⅱ期，AKI Ⅱ期降钙素原、尿量、SOFA评分、TLR4、NGAL、uKIM-1水平高于AKI Ⅰ期，差异有统计学意义(P＜0.05)。TLR4、NGAL、uKIM-1水平与Scr、eGFR均无相关性(P>0.05)。TLR4、NGAL、uKIM-1水平分别与降钙素原、SOFA评分呈正相关，与尿量呈负相关(P＜0.05)。TLR4、NGAL、uKIM-1联合检测脓毒症患者并发AKI的灵敏度、特异度、AUC(95%CI)分别为0.783、0.969、0.900(0.849~0.950)。 结论 脓毒症患者并发AKI存在TLR4、NGAL、uKIM-1水平升高，三者对于判定AKI发生及病情发展具有重要意义，且三者联合检测脓毒症患者并发AKI诊断价值更高。Abstract: Objective To analyze the diagnostic value of toll like receptor 4(TLR4), neutrophil gelatinase-associated lipocalin(NGAL)and urinary kidney injury molecules-1(uKIM-1)in patients with sepsis complicated with acute kidney injury(AKI). Methods 181 patients with sepsis admitted to our hospital from October 2020 to February 2023 were selected. According to whether AKI occurred, they were divided into AKI group with 83 cases(30 cases in AKI stage I, 38 cases in AKI stage Ⅱ, and 15 cases in AKI stage Ⅲ) and the non-AKI group with 98 cases. The TLR4, NGAL, and uKIM-1 levels between the AKI group and the non-AKI group were compared. The levels of serum creatinine(Scr), eGFR, procalcitonin, urine volume, sequential organ failure assessment(SOFA) score, TLR4, NGAL and uKIM-1 in different AKI stages were compared. Pearson was used to analyze the correlation between TLR4, NGAL and uKIM-1 levels and Scr, eGFR, procalcitonin, urine volume and SOFA score. Draw ROC curves to analyze the diagnostic value of TLR4, NGAL, uKIM-1 single and combined detection of AKI in sepsis patients. Results The levels of TLR4, NGAL, uKIM-1, procalcitonin and SOFA score in the AKI group were higher than those in the non-AKI group, and the urine volume was lower than that in the non-AKI group, statistically significant(P < 0.05).There was no significant difference in Scr and eGFR between the two groups (P>0.05). logistic regression results showed that, the increased levels of procalcitonin, urine volume, TLR4, NGAL and uKIM-1 were risk factors for AKI in patients with sepsis, statistically significant(P < 0.05). There was no significant difference in Scr and eGFR among the three groups(P>0.05). The levels of procalcitonin, urine volume, SOFA score, TLR4, NGAL and uKIM-1 in AKI Ⅲ stage were higher than those in AKI Ⅰ and AKI Ⅱ stage, while the levels of procalcitonin, urine volume, SOFA score, TLR4, NGAL and uKIM-1 in AKI Ⅱ stage were higher than those in AKI Ⅰ stage, statistically significant(P < 0.05). The levels of TLR4, NGAL and uKIM-1 were not correlated with Scr and eGFR(P>0.05). The levels of TLR4, NGAL and uKIM-1 were positively correlated with procalcitonin, urine volume and SOFA score, respectively(P < 0.05). The sensitivity, specificity, and AUC(95%CI) of TLR4, NGAL, and uKIM-1 in jointly detecting septic patients with AKI were 0.783, 0.969 and 0.900 (0.849-0.950), respectively. Conclusion The increased levels of TLR4, NGAL and uKIM-1 exist in patients with sepsis complicated with AKI, which are of great significance in determining the occurrence and progression of AKI. The combined detection of these three factors has higher diagnostic value for sepsis patients with concurrent AKI.
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表 1 AKI组、非AKI组的TLR4、NGAL、uKIM-1水平
X±S 组别 例数 TLR4/(ng/mL) NGAL/(ng/mL) uKIM-1/(ng/mL) Scr/ (mg/dL) eGFR/(mL/min/1.73 m2) 降钙素原/(ng/mL) 尿量/(mL/24 h) SOFA评分/分 非AKI组 98 3.93±0.37 100.20±18.96 4.00±0.48 0.96±0.32 67.49±6.89 5.08±1.25 1 923.61±235.59 11.55±4.34 AKI组 83 5.28±1.63 148.57±38.25 5.99±1.83 1.04±0.30 66.56±7.27 7.55±2.97 1 480.22±323.57 13.05±5.36 t - 7.370 10.481 9.637 1.693 0.877 7.046 10.371 1.870 P - ＜0.001 ＜0.001 ＜0.001 0.092 0.381 ＜0.001 ＜0.001 0.039 
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表 2 logistic回归分析影响脓毒症患者并发AKI的危险因素
因素 单因素分析 多因素分析 β SE OR 95%CI P β SE OR 95%CI P 性别 -0.056 0.314 0.945 0.511~1.750 0.858 - - - - - 年龄 0.087 0.299 1.091 0.607~1.961 0.770 - - - - - BMI 0.264 0.300 1.302 0.723~2.342 0.379 - - - - - Scr 0.479 0.301 1.615 0.896~2.913 0.111 - - - - - eGFR -0.259 0.299 0.772 0.429~1.388 0.388 - - - - - 降钙素原 2.413 0.369 11.172 5.418~23.038 ＜0.001 1.600 0.532 4.953 1.744~14.060 0.003 尿量 2.645 0.366 14.083 6.877~28.842 ＜0.001 1.254 0.496 3.504 1.325~9.270 0.012 SOFA评分 0.396 0.301 1.485 0.824~2.678 0.188 - - - - - TLR4 3.031 0.452 20.719 8.536~50.290 ＜0.001 1.826 0.629 6.211 1.809~21.329 0.004 NGAL 3.052 0.398 21.159 9.691~46.195 ＜0.001 1.600 0.524 4.952 1.775~13.818 0.002 uKIM-1 3.832 0.561 46.161 15.378~138.565 ＜0.001 2.129 0.738 8.406 1.979~35.712 0.004
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表 3 不同AKI分期的TLR4、NGAL、uKIM-1水平
X±S 组别 例数 Scr/(mg/dL) eGFR/(mL/min/1.73 m2) 降钙素/(ng/mL) 尿量/mL SOFA评分/分 TLR4/(ng/mL) NGAL/(ng/mL) uKIM-1/(ng/mL) AKI Ⅰ期 30 0.97±0.26 68.26±7.33 5.70±1.37 1 763.52±206.88 7.64±1.68 4.08±0.57 112.35±20.06 4.25±0.59 AKI Ⅱ期 38 1.07±0.30 66.00±7.20 7.10±1.681) 1 439.18±188.591) 14.26±2.751) 5.15±0.861) 158.36±24.181) 6.31±0.941) AKI Ⅲ期 15 1.11±0.35 64.58±7.08 12.38±2.771)2) 1 017.53±156.941)2) 20.80±3.341)2) 8.03±1.341)2) 196.22±26.231)2) 8.66±1.451)2) F - 1.66 1.51 69.04 78.33 441.66 101.63 74.80 112.19 P - 0.196 0.228 ＜0.001 ＜0.001 ＜0.001 ＜0.001 ＜0.001 ＜0.001 与AKI Ⅰ期比较，1)P＜0.05；与AKI Ⅱ期比较，2)P＜0.05。
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表 4 TLR4、NGAL、uKIM-1水平与Scr、eGFR、降钙素原、尿量、SOFA评分的相关性
指标 TLR4 NGAL uKIM-1 r P r P r P Scr 0.118 0.288 0.180 0.103 0.108 0.329 eGFR -0.196 0.076 -0.166 0.133 -0.204 0.064 降钙素原 0.649 ＜0.001 0.591 ＜0.001 0.721 ＜0.001 尿量 -0.626 ＜0.001 -0.695 ＜0.001 -0.719 ＜0.001 SOFA评分 0.705 ＜0.001 0.621 ＜0.001 0.708 ＜0.001
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表 5 TLR4、NGAL、uKIM-1单一及联合检测脓毒症患者并发AKI的诊断价值
变量 灵敏度 特异度 标准误 AUC 95%CI P TLR4 0.594 0.533 0.038 0.402 0.310~0.469 0.021 NGAL 0.601 0.579 0.042 0.410 0.328~0.483 0.018 uKIM-1 0.615 0.598 0.051 0.428 0.351~0.508 0.011 TLR4+NGAL+NLR 0.910 0.871 0.069 0.738 0.650~0.818 ＜0.001
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