首页|基于尿组织金属蛋白酶抑制物2与胰岛素样生长因子结合蛋白7的急性肾损伤风险预测模型构建及其在重症患者中的早期预测价值

基于尿组织金属蛋白酶抑制物2与胰岛素样生长因子结合蛋白7的急性肾损伤风险预测模型构建及其在重症患者中的早期预测价值

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目的 基于尿组织金属蛋白酶抑制物2(TIMP2)与胰岛素样生长因子结合蛋白7(IGFBP7)建立重症患者急性肾损伤(AKI)早期风险预测模型列线图,并验证该模型的预测价值.方法 采用前瞻性观察性研究方法,选择2017年11月至2020年4月江苏省苏北人民医院重症监护病房(ICU)收治的急性呼吸衰竭或循环障碍患者.患者于入ICU 24 h内入组,收集患者基础资料及相关实验室检查指标;同时收集患者尿液,测定生物标志物TIMP2和IGFBP7水平,并计算二者乘积(TIMP2·IGFBP7).按照患者入组12 h内是否发生2级或3级AKI分为非AKI和AKI组,比较两组患者基线特征及尿TIMP2·IGFBP7水平;将单因素分析中P<0.1的指标纳入多因素Logistic回归分析,筛选重症患者12 h内发生2级或3级AKI的独立危险因素,建立风险预测模型列线图,并评价模型的应用价值.结果 最终共纳入206例重症患者,其中54例(占26.2%)在入组12 h内发生2级或3级AKI,152例(占73.8%)未发生.与非AKI组比较,AKI组患者体质量指数(BMI)、入组前血肌酐(SCr)、尿TIMP2·IGFBP7和使用血管活性药物比例更高,AKI额外暴露(入组前使用肾毒性药物)更常见.多因素Logistic 回归分析显示,BMI[优势比(OR)=1.23,95%可信区间(95%CI)为 1.10~1.37,P=0.000]、入组前 SCr(OR=1.01,95%CI 为 1.00~1.02,P=0.042)、使用肾毒性药物(OR=2.84,95%CI 为 1.34~6.03,P=0.007)及尿TIMP2·IGFBP7(OR=2.19,95%CI为1.56~3.08,P=0.000)是重症患者发生2级或3级AKI的独立危险因素.基于上述独立危险因素构建AKI风险预测模型列线图;Bootstrap验证结果显示其在内部验证中表现出良好的区分度及校准度.受试者工作特征曲线(ROC曲线)分析显示,单独尿TIMP2·IGFBP7预测重症患者12 h内发生2级或3级AKI的ROC曲线下面积(AUC)为0.74(95%CI为0.66~0.83),最佳截断值为1.40(μg/L)2/1 000(敏感度为66.7%,特异度为85.0%),且纳入尿TIMP2·IGFBP7模型的预测效能明显优于未纳入尿TIMP2·IGFBP7模型[AUC(95%CI):0.85(0.79~0.91)比 0.77(0.70~0.84),P=0.005],净重新分类指数(NRI)为 0.29(95%CI为 0.08~0.50,P=0.008),综合判别改善指数(IDI)为 0.13(95%CI 为 0.07~0.19,P<0.001).结论 基于尿TIMP2·IGFBP7建立的AKI风险预测模型具有较高的临床价值,有望用于早期预测重症患者AKI的发生.
Construction of a risk predictive model of acute kidney injury based on urinary tissue inhibitor of metalloproteinase 2 and insulin-like growth factor-binding protein 7 and its early predictive value in critically ill patients
Objective To establish a risk predictive model nomogram of acute kidney injury(AKI)in critically ill patients by combining urinary tissue inhibitor of metalloproteinase 2(TIMP2)and insulin-like growth factor-binding protein 7(IGFBP7),and to verify the predictive value of the model.Methods A prospective observational study was conducted.The patients with acute respiratory failure or circulatory disorder admitted to the intensive care unit(ICU)of Northern Jiangsu People's Hospital from November 2017 to April 2020 were enrolled.The patients were enrolled within 24 hours of ICU admission,and their general conditions and relevant laboratory test indicators were collected.At the same time,urine was collected to determine the levels of biomarkers TIMP2 and IGFBP7,and TIMP2·IGFBP7 was calculated.Patients were divided into non-AKI and AKI groups according to whether grade 2 or 3 AKI occurred within 12 hours after enrollment.The general clinical data and urinary TIMP2·IGFBP7 levels of patients between the two groups were compared.The indicators with P<0.1 in univariate analysis were included in the multivariate Logistic regression analysis to obtain the independent risk factors for grade 2 or 3 AKI within 12 hours in critical patients.An AKI risk predictive model nomogram was established,and the application value of the model was evaluated.Results A total of 206 patients were finally enrolled,of whom 54(26.2%)developed grade 2 or 3 AKI within 12 hours of enrollment,and 152(73.8%)did not.Compared with the non-AKI group,the patients in the AKI group had higher body mass index(BMI),pre-enrollment serum creatinine(SCr),urinary TIMP2·IGFBP7 and proportion of using vasoactive drugs,and additional exposure to AKI(use of nephrotoxic drugs before enrollment)was more common.Multivariate Logistic regression analysis showed that BMI[odds ratio(OR)=1.23,95%confidence interval(95%CI)was 1.10-1.37,P=0.000],pre-enrollment SCr(OR=1.01,95%CI was 1.00-1.02,P=0.042),use of nephrotoxic drugs(OR=2.84,95%CI was 1.34-6.03,P=0.007)and urinary TIMP2·IGFBP7(OR=2.19,95%CI was 1.56-3.08,P=0.000)was an independent risk factor for the occurrence of grade 2 or 3 AKI in critical patients.An AKI risk predictive model nomogram was constructed based on the independent risk factors of AKI.Bootstrap validation results showed that the model had good discrimination and calibration in internal validation.Receiver operator characteristic curve(ROC curve)analysis showed that the area under the ROC curve(AUC)of urinary TIMP2·IGFBP7 alone in predicting grade 2 or 3 AKI within 12 hours in critical patients was 0.74(95%CI was 0.66-0.83),the optimal cut-off value was 1.40(μg/L)2/1 000(sensitivity was 66.7%,specificity was 85.0%),and the predictive performance of the model incorporating urinary TIMP2·IGFBP7 was significantly better than that of the model without urinary TIMP2·IGFBP7[AUC(95%CI):0.85(0.79-0.91)vs.0.77(0.70-0.84),P=0.005],net reclassification index(NRI)was 0.29(95%CI was 0.08-0.50,P=0.008),integrated discrimination improvement(IDI)was 0.13(95%CI was 0.07-0.19,P<0.001).Conclusion The AKI risk predictive model based on urinary TIMP2·IGFBP7 has high clinical value and is expected to be used to early predict the occurrence of AKI in critically ill patients.

Acute kidney injuryTissue inhibitor of metalloproteinase 2Insulin-like growth factor-binding protein 7Nomogram

王海霞、牟洪宾、许晓兰、郑瑞强

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扬州大学附属苏北人民医院(江苏省苏北人民医院)重症医学科,江苏扬州 225001

扬州大学附属苏北人民医院(江苏省苏北人民医院)血液净化中心,江苏扬州 225001

急性肾损伤 组织金属蛋白酶抑制物2 胰岛素样生长因子结合蛋白7 列线图

江苏省医学重点学科建设项目(十四五)

JSDW202217

2024

中华危重病急救医学
中华医学会

中华危重病急救医学

CSTPCD北大核心
影响因子:3.049
ISSN:2095-4352
年,卷(期):2024.36(4)