总胆红素水平对脓毒症患者发生急性肾损伤的影响及其与短期预后的关联: 一项基于MIMIC-Ⅳ数据库的回顾性队列研究

The impact of total bilirubin levels on acute kidney injury in sepsis patients and its association with short-term outcomes: a retrospective cohort study based on the MIMIC-Ⅳ database

摘要:

目的探讨脓毒症患者总胆红素水平对脓毒症相关急性肾损伤(sepsis-associated acute kidney injury, SA-AKI)发生风险的影响，并分析其与患者短期预后的关联。 方法使用重症监护医疗信息数据库(Medical Information Mart for Intensive Care-Ⅳ, MIMIC-Ⅳ-2.2)数据进行回顾性队列研究。主要结局是在重症监护病房(intensive care unit, ICU)脓毒症患者7 d内新发的AKI及28 d全因死亡率，暴露是入住ICU的脓毒症患者24 h内总胆红素水平的初始测量。采用多因素Logistic回归模型和限制性立方样条(restricted cubic spline regression, RCS)分析评估总胆红素与SA-AKI发生风险的相关性，并且还进行了基于不同亚组的分层分析。使用Kaplan-Meier生存曲线分析患者28 d的生存率。 结果9 834例患者纳入本研究，其中SA-AKI患者7 159例。多因素Logistic回归模型调整相关混杂因素分析表明: 总胆红素作为连续变量时，在模型1中总胆红素每升高10 mg/L，SA-AKI风险升高10.2%(OR=1.102，95%CI: 1.074~1.131，P<0.001)；在模型2中总胆红素每升高10 mg/L，SA-AKI风险升高10.8%(OR=1.108，95%CI: 1.079~1.138，P<0.001)；在模型3中总胆红素每升高10 mg/L，SA-AKI风险升高5.4%(OR=1.054，95%CI: 1.021~1.087，P=0.001)。同样，当总胆红素水平按三分位数分类时，在各个模型中，随着三分位数增加，SA-AKI发生风险呈持续上升趋势。RCS曲线分析显示，总胆红素水平与SA-AKI发生风险呈线性关系。Kaplan-Meier生存曲线分析显示，随着总胆红素水平的升高，脓毒症患者28 d的生存率显著降低。 结论总胆红素水平与SA-AKI发生风险呈线性关系，且与短期不良预后显著相关，需要更大规模的前瞻性研究来证实这些发现。

Abstract:

ObjectiveTo investigate the impact of total bilirubin levels on the risk of sepsis-associated acute kidney injury(SA-AKI) in patients with sepsis and analyze its association with short-term prognosis. MethodsIt was a retrospective cohort study and the data were obtained from the Medical Information Mart for Intensive Care-Ⅳ(MIMIC-Ⅳ-2.2) database. The primary outcomes were the incidence of new-onset AKI within 7 days and 28-day all-cause mortality in sepsis patients admitted to the intensive care unit(ICU), and the exposure was the initial measurement of total bilirubin levels within 24 hours of admission to the ICU in patients with sepsis. Multivariate logistic regression model and restricted cubic spline regression(RCS) analysis were used to evaluate the association between total bilirubin and the risk of SA-AKI, and stratified analysis based on different subgroups was performed. The 28-day survival rate was analyzed using Kaplan-Meier survival curve. ResultsA total of 9 834 patients were included in the study, and 7 159 patients developed SA-AKI. Multivariate logistic regression model with adjustment for correlation confounders showed that: when total bilirubin was used as a continuous type variable, the risk of SA-AKI increased by 10.2% for every 10 mg/L increase in total bilirubin in model 1(OR=1.102, 95%CI: 1.074-1.131, P<0.001); the risk of SA-AKI increased by 10.8% for every 10 mg/L increase in total bilirubin in model 2(OR=1.108, 95%CI: 1.079-1.138, P<0.001); the risk of SA-AKI increased by 5.4% for every 10 mg/L increase in total bilirubin in model 3(OR=1.054, 95%CI: 1.021-1.087, P=0.001). Similarly, when total bilirubin was categorized by tertiles, the risk of SA-AKI continued to increase with the increase of the tertiles of total bilirubin in each model. The RCS curve analysis showed a linear relationship between total bilirubin level and the risk of SA-AKI. In addition, Kaplan-Meier survival curve analysis showed that the 28-day survival rate was significantly reduced with the increase of total bilirubin levels in patients with sepsis. ConclusionTotal bilirubin levels exhibit a linear relationship with the risk of SA-AKI and are significantly associated with poor short-term prognosis. Larger prospective studies are required to confirm these findings.