儿童活体肝移植术后早期急性肾损伤的危险因素和生存分析

Risk factors and survival analysis of early acute kidney injury after pediatric living donor liver transplantation

目的探讨儿童活体肝移植术后早期急性肾损伤(acute kidney injury,AKI)的危险因素和对受者预后的影响。方法回顾性分析2018年1月至2019年12月在天津市第一中心医院接受择期活体肝移植术的201例儿童受者的临床资料。并根据2012年改善全球肾脏病预后组织(KDIGO)标准诊断术后AKI并分级。根据移植术后7 d内是否发生AKI,将全部受者分为AKI组(64例)和非AKI组(137例)。比较两组受者的临床资料,将差异有统计学意义的单因素纳入二元logistic回归模型进行多因素分析,明确儿童活体肝移植术后早期AKI发生的独立危险因素。比较两组受者的术后机械通气时间、ICU停留时间、总住院时间、住院期间病死率和术后3年病死率等预后指标,并采用Kaplan-Meier法对不同AKI分级的儿童受者进行生存分析。结果本研究201例儿童活体肝移植受者中,有64例(31.8%)在术后7 d内发生AKI。其中,1级31例(48.4%),2级14例(21.9%),3级19例(29.7%)。单因素分析结果显示,两组受者的年龄、术前儿童终末期肝病评分、原发病是否为胆道闭锁、总胆红素、血清胱抑素C、手术时间和失血量差异有统计学意义(P<0.001、<0.001、0.002、<0.001、<0.001、<0.001和<0.001)。多因素分析结果显示,总胆红素(OR=1.154,95%CI:1.068~1.248,P<0.001)、血清胱抑素C(OR=2.532,95%CI:1.627~3.939,P<0.001)、手术时间(OR=1.174,95%CI:1.064~1.295,P=0.001)和失血量(OR=1.210,95%CI:1.095~1.337,P<0.001)是儿童活体肝移植受者术后7 d内发生AKI的独立危险因素。AKI组受者术后机械通气时间和ICU停留时间分别389 min和3 d,较非AKI组的178 min和2 d长,差异均有统计学意义(P值均<0.001);AKI组受者住院期间病死率为7.8%(6/64),较非AKI组的0.7%(1/137)高,差异有统计学意义(P=0.002)。住院期间非AKI组受者的存活率为99.3%(136/137);AKI组中发生1、2、3级AKI受者的存活率分别为96.8%(30/31)、92.9%(13/14)、78.9%(15/19)。术后3年非AKI组受者存活率为94.2%(129/137);AKI组中发生1、2、3级AKI受者的存活率分别为96.8%(30/31)、78.6%(11/14)、73.7%(14/19)。生存分析结果显示,术后7 d内非AKI组,AKI组中发生1、2级、3级AKI的受者在住院期间和术后3年的存活率均逐渐降低,差异有统计学意义(χ^(2)=21.102,P<0.001;χ^(2)=13.316,P=0.004)。结论AKI是儿童活体肝移植术后常见并发症,对受者预后产生不利影响。术前总胆红素和血清胱抑素C水平升高、手术时间延长和术中失血量增多会增加儿童受者术后早期发生AKI的风险。

Objective To explore risk factors of early acute kidney injury(AKI)after pediatric living donor liver transplantation(LT)and examine the effects on the prognosis of recipients.Methods From January 2018 to December 2019,the relevant clinical data were retrospectively reviewed for 201 pediatric recipients of elective living donor LT.Post-LT AKI recipients were diagnosed and categorized according to Kidney Disease:Improving Global Outcomes(KDIGO)criteria(2012).Based upon the presence or absence of AKI within 7 days post-LT,they were assigned into two groups of AKI(64 cases)and non-AKI(137 cases).Baseline profiles,preoperative results of major laboratory tests and operation-related parameters were compared between two groups.Univariate variables with statistical differences were included into binary Logistic regression model for multivariate analysis to identify the independent risk factors of early AKI post-LT.Prognostic data of recipients such as postoperative mechanical ventilation time,intensive care unit(ICU)stay time,total hospitalization stay,in-hospital mortality and 3-year postoperative mortality were compared between two groups.Survival analysis was conducted for pediatric recipients with different AKI grades.Results The incidence of AKI within 7 days post-LT was 31.8%(64/201).Univariate analysis revealed significant inter-group differences in age,preoperative PELD score,diagnosis of biliary atresia,total bilirubin,cystatin C,operative duration and volume of blood loss(P<0.001,P<0.001,P=0.002,P<0.001,P<0.001,P<0.001&P<0.001).Multi-factorial analysis showed that total bilirubin(OR=1.154,95%CI:1.068-1.248,P<0.001),cystatin C(OR=2.532,95%CI:1.627-3.939,P<0.001),operative duration(OR=1.174,95%CI:1.064-1.295,P=0.001)and volume of blood loss(OR=1.210,95%CI:1.095-1.337,P<0.001)were independent risk factors of AKI within 7 days post-LT.As compared with non-AKI group,postoperative mechanical ventilation time and ICU stay time became markedly extended(178 vs 389 min,P<0.001;2 vs 3 day,P<0.001)and mortality during hospitalization rose sharply(0.7%vs 7.8%,P=0.002)in AKI group.The survival rates of recipients during hospitalization in group non-AKI/AKI were 99.3%(136/137)and 96.8%(30/31,grade 1),92.9%(13/14,grade 2),78.9%(15/19,grade 3).The survival rates of recipients 3 years post-LT in group non-AKI/AKI were 94.2%(129/137)and 96.8%(30/31,grade 1),78.6%(11/14,grade 2),73.7%(14/19,grade 3).Results of survival analysis indicated that,in group non-AKI and AKI(geade 1,2,3),survival rate of recipients during hospitalization and 3 years post-LT declined gradually(χ^(2)=21.102,P<0.001;χ^(2)=13.316,P=0.004).Conclusion As one common complication after pediatric living donor LT,AKI adversely affects the prognosis of recipients.Elevated preoperative levels of total bilirubin and cystatin C,prolonged operative duration and greater volume of intraoperative blood loss may boost the postoperative risk of early AKI in pediatric recipients.