血磷水平对接受持续性肾脏替代治疗脓毒性急性肾损伤患者预后的影响

The influence of serum phosphate level on the prognosis of septic patients with acute kidney injury requiring continuous renal replacement therapy

目的探讨血磷水平与接受持续性肾脏替代治疗(CRRT)的脓毒性急性肾损伤(AKI)患者预后的关系。方法收集2013年1月至2019年9月在海南医学院第二附属医院ICU住院并行CRRT治疗的脓毒性AKI患者的临床资料进行回顾性分析。根据患者CRRT后28 d转归分为存活组和死亡组,比较两组患者CRRT前的一般情况、疾病组成、实验室指标、生命体征、急性生理学与慢性健康状况评分系统Ⅱ(APACHEⅡ)评分、序贯器官衰竭评估(SOFA)评分及血磷水平。分析血清磷水平与APACHEⅡ评分和SOFA评分的相关性。按血磷水平四分位数间距分为Q1(≤1.29 mmol/L)、Q2(1.30~1.78 mmol/L)、Q3(1.79~2.22 mmol/L)及Q4(≥2.23 mmol/L)四个区间,比较不同区间28 d病死率的差异。采用Kaplan-Meier生存曲线分析不同区间患者28 d累积生存率。采用多因素Cox比例风险回归模型分析接受CRRT的脓毒性AKI患者28 d死亡的独立危险因素。结果共纳入758例接受CRRT的脓毒性AKI患者,其中473例(62.4%)患者死亡(死亡组),285例(37.6%)患者存活(存活组)。与存活组比较,死亡组患者较少伴有高血压、糖尿病及慢性阻塞性肺疾病(COPD)。死亡组患者APACHEⅡ评分、SOFA评分、白细胞计数、C-反应蛋白、血磷水平及应用机械通气与血管活性药物比率明显高于存活组[APACHEⅡ评分(分):28.4±8.0 vs.25.7±7.4,SOFA评分(分):12.9±3.2 vs.10.5±3.5,白细胞计数(×109/L):10.9(4.8,18.2)vs.12.2(8.9,19.3),C-反应蛋白(mg/L):110.4(30.7,129.6)vs.93.2(20.7,118.6),血磷(mmol/L):1.9±0.7 vs.1.7±0.7,机械通气:83.9%vs.70.9%,血管活性药物:66.8%vs.56.9%],而体质量指数(BMI)、平均动脉压(MAP)、血肌酐、白蛋白水平及CRRT前6 h尿量明显降低[BMI(kg/m2):23.3±4.6 vs.24.1±4.0,MAP(mm Hg):75.9±13.7 vs.80.9±15.0,血肌酐(μmol/L):198.9(144.1,274.9)vs.226.3(148.1,313.8),白蛋白(g/L):25.1±5.5 vs.27.2±6.1,尿量(mL):25.0(0,76.3)vs.53.5(15,130.0)],差异有统计学意义(P<0.01或0.05)。相关性分析显示,血磷水平与APACHEⅡ评分(r=0.160,P<0.001)和SOFA评分(r=0.094,P=0.008)呈明显正相关。Q1、Q2、Q3及Q4四个区间的28 d病死率分别为54.3%、59.6%、61.3%及75.9%,差异有统计学意义(χ^2=19.674,P<0.001)。Kaplan-Meier生存曲线显示区间越高的患者生存状况越差(χ^2=32.147,P<0.001)。多因素Cox比例风险回归模型分析显示,高APACHEⅡ评分(HR=1.014,95%CI 1.001~1.027,P=0.030)、高SOFA评分(HR=1.160,95%CI 1.123~1.198,P<0.001)、Q3(HR=1.403,95%CI 1.083~1.816,P=0.010)、Q4(HR=1.988,95%CI 1.530~2.548,P≤0.001)及应用血管活性药物(HR=1.001,95%CI 1.000~1.002,P=0.038)为接受CRRT治疗的脓毒性AKI患者28 d死亡的独立危险因素,而高BMI(HR=0.977,95%CI 0.956~0.998,P=0.035)、高MAP(HR=0.988,95%CI 0.981~0.994,P<0.001)、高CRRT前6 h尿量(HR=0.998,95%CI 0.997~0.999,P=0.005)、高血肌酐(HR=0.817,95%CI 0.758~0.880,P<0.001)及高白蛋白(HR=0.747,95%CI 0.634~0.879,P<0.001)为独立保护因素。结论血磷水平与接受CRRT治疗的脓毒性AKI患者病情严重程度密切相关,高血磷水平是其28 d死亡的独立危险因素。

Objective To investigate the relationship between serum phosphate level and the prognosis of septic patients with acute kidney injury(AKI)requiring continuous renal replacement therapy(CRRT).Methods The clinical data of septic patients with AKI requiring CRRT admitted to the Intensive Care Unit(ICU)of the Second Affiliated Hospital of Hainan Medical College from January 2013 to September 2019 were retrospectively analyzed.The patients were divided into survival group and death group according to the outcomes after 28-day CRRT.General information,disease composition,laboratory indexes,vital signs,the acute physiology and chronic health evaluationⅡ(APACHEⅡ)score,sequential organ failure assessment(SOFA)score and serum phosphate level before CRRT were compared between the two groups.The correlation of serum phosphate level with APACHEⅡscore and SOFA score was analyzed.Based on serum phosphate level,patients were classified into four quartiles[Q1(≤1.29 mmol/L),Q2(1.30-1.78 mmol/L),Q3(1.79-2.22 mmol/L)and Q4(≥2.23 mmol/L)],and 28-day mortality between different intervals was compared.Kaplan-Meier survival curve was performed to analyze 28-day cumulative survival rates in different intervals.The independent risk factors for the 28-day dead in septic patients with AKI requiring CRRT were analyzed by the Cox proportional hazards regression model.Results A total of 758 septic patients with AKI requiring CRRT were enrolled.Among them,473(62.4%)patients died(death group),and 285(37.6%)survived(survival group).Compared with the survival group,the death group had less hypertension,diabetes mellitus and chronic obstructive pulmonary disease(COPD).The APACHEⅡscore,SOFA score,leukocyte,C-reactive protein,serum phosphorus,the proportion of mechanical ventilation and vasoactive drugs in the dead group were significantly higher than those in the survival group[APACHEⅡ(score):28.4±8.0 vs.25.7±7.4,SOFA(score):12.9±3.2 vs.10.5±3.5,leukocyte(×109/L):10.9(4.8,18.2)vs.12.2(8.9,19.3),C-reactive protein(mg/L):110.4(30.7,129.6)vs.93.2(20.7,118.6),serum phosphorus(mmol/L):1.9±0.7 vs.1.7±0.7,mechanical ventilation:83.9%vs.70.9%,vasoactive drugs:66.8%vs.56.9%],while body mass index(BMI),mean arterial pressure(MAP),serum creatinine,albumin and urine volume during the first 6 h before CRRT were significantly lower than those in the survival group[BMI(kg/m2):23.3±4.6 vs.24.1±4.0,MAP(mm Hg):75.9±13.7 vs.80.9±15.0,serum creatinine(μmol/L):198.9(144.1,274.9)vs.226.3(148.1,313.8),albumin(g/L):25.1±5.5 vs.27.2±6.1,urine volume(mL):25.0(0,76.3)vs.53.5(15,130.0)],with statistically significant differences(all P<0.01 or 0.05).The correlation analysis showed that serum phosphorus was significantly positively correlated with APACHEⅡscore(r=0.160,P<0.001)and SOFA score(r=0.094,P=0.008).The 28-day mortality of Q1,Q2,Q3 and Q4 were 54.3%,59.6%,61.3%and 75.9%,respectively,with statistically significant differences(χ^2=19.674,P<0.001).Kaplan-Meier survival curve showed that the patients with higher interval had worse survival(χ^2=32.147,P<0.001).Multivariate Cox regression analysis indicated that high APACHEⅡscore(HR=1.014,95%CI 1.001-1.027,P=0.030),high SOFA score(HR=1.160,95%CI 1.123-1.198,P<0.001),Q3(HR=1.403,95%CI 1.083-1.816,P=0.010),Q4(HR=1.988,95%CI 1.530-2.548,P≤0.001)and using vasoactive drug(HR=1.001,95%CI 1.000-1.002,P=0.038)were independent risk factors for 28-day mortality in septic patients with AKI requiring CRRT,while high BMI(HR=0.977,95%CI 0.956-0.998,P=0.035),high MAP(HR=0.988,95%CI 0.981-0.994,P<0.001),high urine volume during the first 6 h before CRRT(HR=0.998,95%CI 0.997-0.999,P=0.005),high serum creatinine(HR=0.817,95%CI 0.758-0.880,P<0.001)and high albumin(HR=0.747,95%CI 0.634-0.879,P<0.001)were independent protective factors.Conclusion Serum phosphorus level is closely related to the severity in septic patients with AKI requiring CRRT,and high serum phosphorus level was independent risk factor for 28-day death.