Early predictive value of high density lipoprotein cholesterol for secondary acute kidney injury in sepsis patients
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摘要:
目的 探讨脓毒症患者高密度脂蛋白胆固醇（HDL-C）水平的变化及其对该类患者继发急性肾损伤（AKI）的早期预测价值。 方法 采用回顾性病例系列研究方法。2019年6月—2021年6月，河北医科大学第二医院收治232例符合入选标准的脓毒症患者，其中男126例、女106例，年龄24~71岁。依据是否继发AKI，将患者分为非AKI组（158例）和AKI组（74例）。对比2组患者入院时性别、年龄、身体质量指数（BMI）、体温、心率、原发感染部位、合并基础疾病情况、急性生理学和慢性健康状况评价Ⅱ（APACHE Ⅱ）评分及脓毒症相关性器官功能衰竭评价（SOFA）评分，确诊脓毒症时检测的血清C反应蛋白（CRP）、降钙素原、肌酐、胱抑素C及HDL-C水平，对数据进行独立样本t检验、χ2检验。对2组比较差异有统计学意义的指标进行多因素logistic回归分析，筛选影响232例脓毒症患者继发AKI的独立危险因素，并以独立危险因素为基础构建联合预测模型。绘制独立危险因素与联合预测模型预测232例脓毒症患者继发AKI的受试者操作特征（ROC）曲线，计算曲线下面积（AUC）及最佳阈值与最佳阈值下的敏感度、特异度。采用Delong检验对前述AUC的质量进行比较，采用χ2检验对最佳阈值下的敏感度和特异度进行比较。 结果 2组患者性别、年龄、BMI、体温、心率、原发感染部位、合并基础疾病以及CRP水平均相近（P>0.05）；AKI组患者降钙素原、肌酐、胱抑素C、APACHE Ⅱ评分及SOFA评分均明显高于非AKI组（t值分别为-3.21、-16.14、-12.75、-11.13、-12.88， P<0.01），HDL-C水平显著低于非AKI组（t=6.33，P<0.01）。多因素logistic回归分析显示，肌酐、胱抑素C、HDL-C是232例脓毒症患者继发AKI的独立危险因素（比值比分别为2.45、1.68、2.12，95%置信区间分别为1.38~15.35、1.06~3.86、0.86~2.56，P<0.01）。肌酐、胱抑素C、HDL-C、联合预测模型预测232例脓毒症患者继发AKI的ROC的AUC分别为0.69、0.79、0.89、0.93（95%置信区间分别为0.61~0.76、0.72~0.85、0.84~0.92、0.89~0.96，P值均<0.01），最佳阈值分别为389.53 μmol/L、1.56 mg/L、0.63 mmol/L、0.48，最佳阈值下的敏感度分别为76.6%、81.4%、89.7%、95.5%，最佳阈值下的特异度分别为78.6%、86.7%、88.6%、96.6%。胱抑素C的AUC质量明显优于肌酐（z=2.34，P<0.05），HDL-C的AUC质量及最佳阈值下的敏感度、特异度均明显优于胱抑素C（z=3.33，χ2值分别为6.43、7.87，P<0.01）与肌酐（z=5.34，χ2值分别为6.32、6.41，P<0.01），联合预测模型的AUC质量及最佳阈值下的敏感度、特异度均明显优于肌酐、胱抑素C、HDL-C（z值分别6.18、4.50、2.06，χ2值分别5.31、7.23、3.99，6.56、7.34、4.00，P<0.05或P<0.01）。 结论 脓毒症继发AKI患者HDL-C水平较未继发AKI患者明显降低，该指标是脓毒症患者继发AKI的独立危险因素，其诊断价值优于肌酐和胱抑素C，前述3个指标联合对脓毒症患者继发AKI的预测价值更高。 Abstract:Objective To investigate the changes of high density lipoprotein cholesterol (HDL-C) in sepsis patients and its early predictive value for secondary acute kidney injury (AKI) in such patients. Methods A retrospective case series study was conducted. From June 2019 to June 2021, 232 sepsis patients who met the inclusion criteria were admitted to the Second Hospital of Hebei Medical University, including 126 males and 106 females, aged 24 to 71 years. According to whether complicating secondary AKI, the patients were divided into non-AKI group (n=158) and AKI group (n=74). Data of patients between the two groups were compared and statistically analyzed with independent sample t test or chi-square test, including the sex, age, body mass index (BMI), body temperature, heart rate, primary infection site, combined underlying diseases, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score and sepsis-related organ failure assessment (SOFA) score at admission, and the serum levels of C-reactive protein (CRP), procalcitonin, creatinine, cystatin C, and HDL-C measured at diagnosis of sepsis. The multivariate logistic regression analysis was performed on the indicators with statistically significant differences between the two groups to screen the independent risk factors for developing secondary AKI in 232 sepsis patients, and the joint prediction model was established based on the independent risk factors. The receiver operating characteristic (ROC) curve of the independent risk factors and the joint prediction model predicting secondary AKI in 232 sepsis patients were drawn, and the area under the curve (AUC), the optimal threshold, and the sensitivity and specificity under the optimal threshold were calculated. The quality of the above-mentioned AUC was compared by Delong test, and the sensitivity and specificity under the optimal threshold were compared using chi-square test. Results The sex, age, BMI, body temperature, heart rate, primary infection site, combined underlying diseases, and CRP level of patients between the two groups were similar (P>0.05). The procalcitonin, creatinine, cystatin C, and scores of APACHE Ⅱ and SOFA of patients in AKI group were all significantly higher than those in non-AKI group (with t values of -3.21, -16.14, -12.75, -11.13, and -12.88 respectively, P<0.01), while the HDL-C level of patients in AKI group was significantly lower than that in non-AKI group (t=6.33, P<0.01). Multivariate logistic regression analysis showed that creatinine, cystatin C, and HDL-C were the independent risk factors for secondary AKI in 232 sepsis patients (with odds ratios of 2.45, 1.68, and 2.12, respectively, 95% confidence intervals of 1.38-15.35, 1.06-3.86, and 0.86-2.56, respectively, P<0.01). The AUCs of ROC curves of creatinine, cystatin C, HDL-C, and the joint prediction model for predicting secondary AKI in 232 sepsis patients were 0.69, 0.79, 0.89, and 0.93, respectively (with 95% confidence intervals of 0.61-0.76, 0.72-0.85, 0.84-0.92, and 0.89-0.96, respectively, P values all below 0.01); the optimal threshold were 389.53 μmol/L, 1.56 mg/L, 0.63 mmol/L, and 0.48, respectively; the sensitivity under the optimal threshold were 76.6%, 81.4%, 89.7%, and 95.5%, respectively; the specificity under the optimal threshold values were 78.6%, 86.7%, 88.6%, and 96.6%, respectively. The AUC quality of cystatin C was significantly better than that of creatinine (z=2.34, P<0.05), the AUC quality and sensitivity and specificity under the optimal threshold of HDL-C were all significantly better than those of cystatin C (z=3.33, with χ2 values of 6.43 and 7.87, respectively, P<0.01) and creatinine (z=5.34, with χ2 values of 6.32 and 6.41, respectively, P<0.01); the AUC quality and sensitivity and specificity under the optimal threshold of the joint prediction model were all significantly better than those of creatinine, cystatin C, and HDL-C (with z values of 6.18, 4.50, and 2.06, respectively, χ2 values of 5.31, 7.23, 3.99, 6.56, 7.34, and 4.00, respectively, P<0.05 or P<0.01). Conclusions HDL-C level in sepsis patients with secondary AKI is significantly lower than that in patients without secondary AKI. This is an independent risk factor for secondary AKI in sepsis patients with a diagnostic value being superior to that of creatinine and cystatin C. The combination of the aforementioned three indicators would have higher predicative valuable for secondary AKI in sepsis patients. -
Key words:
- Sepsis /
- Prognosis /
- Acute kidney injury /
- Forecasting /
- High density lipoprotein cholesterol /
- Creatinine /
- Cystatin C
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1 3种独立危险因素与联合预测模型预测232例脓毒症患者继发急性肾损伤的受试者操作特征曲线
注：HDL-C为高密度脂蛋白胆固醇；联合预测模型以肌酐、胱抑素C与HDL-C为基础
表1 2组脓毒症患者临床资料比较
组别 例数 性别（例） 年龄（岁， BMI（kg/m2， 体温（℃， 心率（次/min， 合并基础疾病（例） 高血压 冠心病 糖尿病 COPD 脑血管疾病 脑血管疾病 男 女 非AKI组 158 82 76 54±12 21.8±2.9 38.5±0.9 97±17 57 28 32 15 22 10 AKI组 74 44 30 55±9 22.5±3.6 38.8±0.8 101±18 22 13 21 10 13 8 统计量值 χ2=1.16 t=-0.71 t=-1.43 t=-1.60 t=-1.79 χ2=0.90 χ2=0.01 χ2=1.89 χ2=0.85 χ2=0.52 χ2=1.41 P值 0.323 0.477 0.153 0.109 0.073 0.375 0.977 0.182 0.370 0.555 0.292 注：AKI为急性肾损伤，BMI为身体质量指数，COPD为慢性阻塞性肺疾病，APACHE Ⅱ为急性生理学和慢性健康状况评价Ⅱ，SOFA为脓毒症相关性器官功能衰竭评价，CRP为C反应蛋白，HDL-C为高密度脂蛋白胆固醇 
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表2 232例脓毒症患者继发急性肾损伤的多因素logistic回归分析结果
因素 回归系数 标准误 比值比 95%置信区间 P值 降钙素原（ng/mL） 0.21 0.33 0.59 0.56~0.71 0.055 肌酐（μmol/L） 4.13 4.62 2.45 1.38~15.35 <0.001 胱抑素C（mg/L） 0.91 0.53 1.68 1.06~3.86 <0.001 HDL-C（mmol/L） 1.02 0.41 2.12 0.86~2.56 <0.001 APACHE Ⅱ评分（分） 0.07 0.02 0.96 0.91~1.53 0.083 SOFA评分（分） 0.28 0.15 1.31 0.78~1.72 0.112 注：HDL-C为高密度脂蛋白胆固醇，APACHE Ⅱ为急性生理学和慢性健康状况评价Ⅱ，SOFA为脓毒症相关性器官功能衰竭评价
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表3 3种独立危险因素与联合预测模型对232例脓毒症患者继发AKI预测的受试者操作特征曲线的曲线下面积质量及最佳阈值下敏感度和特异度比较
对比因素或模型 曲线下面积 敏感度 特异度 曲线下面积差值 标准误 95%置信区间 z值 P值 χ2值 P值 χ2值 P值 肌酐与胱抑素C 0.10 0.05 0.02~0.20 2.34 0.019 3.43 0.213 3.22 0.108 肌酐与HDL-C 0.20 0.04 0.13~0.28 5.34 0.001 6.32 0.001 6.41 0.001 肌酐与联合预测模型 0.24 0.04 0.17~0.32 6.18 0.001 5.31 0.001 6.56 0.001 胱抑素C与HDL-C 0.10 0.03 0.04~0.16 3.33 0.001 6.43 0.001 7.87 0.001 胱抑素C与联合预测模型 0.14 0.03 0.08~0.20 4.50 0.001 7.23 0.001 7.34 0.001 HDL-C与联合预测模型 0.04 0.02 0.01~0.07 2.06 0.039 3.99 0.028 4.00 0.023 注：AKI为急性肾损伤，HDL-C为高密度脂蛋白胆固醇；联合预测模型以肌酐、胱抑素C与HDL-C为基础
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脱细胞真皮基质（ADM） 重症监护病房（ICU） 动脉血氧分压（PaO2） 丙氨酸转氨酶（ALT） 白细胞介素（IL） 磷酸盐缓冲液（PBS） 急性呼吸窘迫综合征（ARDS） 角质形成细胞（KC） 反转录-聚合酶链反应（RT-PCR） 天冬氨酸转氨酶（AST） 半数致死烧伤面积（LA50） 全身炎症反应综合征（SIRS） 集落形成单位（CFU） 内毒素/脂多糖（LPS） 超氧化物歧化酶（SOD） 细胞外基质（ECM） 丝裂原活化蛋白激酶（MAPK） 动脉血氧饱和度（SaO2） 表皮生长因子（EGF） 最低抑菌浓度（MIC） 体表总面积（TBSA） 酶联免疫吸附测定（ELISA） 多器官功能障碍综合征（MODS） 转化生长因子（TGF） 成纤维细胞（Fb） 多器官功能衰竭（MOF） 辅助性T淋巴细胞（Th） 成纤维细胞生长因子（FGF） 一氧化氮合酶（NOS） 肿瘤坏死因子（TNF） 3-磷酸甘油醛脱氢酶（GAPDH） 负压伤口疗法（NPWT） 血管内皮生长因子（VEGF） 苏木精-伊红（HE） 动脉血二氧化碳分压（PaCO2） 负压封闭引流（VSD）
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