肝移植术后高尿酸血症发病率及危险因素分析:单中心回顾性研究

Risk factors of hyperuricemia after liver transplantation:a single center retrospective analysis

目的探讨肝移植术后高尿酸血症发病率及危险因素。方法对2018年1月至2019年5月于南京大学医学院附属鼓楼医院行肝脏移植的164例肝移植受者进行回顾性分析。收集的人口统计学和生物化学数据包括性别、年龄、体重指数、术前血尿酸、肝移植手术时间、术中出血量、术中尿量、血尿酸、术后第1周平均他克莫司全血谷浓度、他克莫司全血谷浓度变异度,移植后1周、1个月、3个月、6个月肌酐清除率(creatinine clearance rate,CCr)。根据肝移植术后6个月血尿酸水平将患者分为正常组和高尿酸血症组,比较各组患者上述指标的差异。采用Logistic多因素回归分析肝移植受者高尿酸血症的影响因素。结果最终共纳入81例患者,术后6个月高尿酸血症发生率为48.15%(39/81),高尿酸血症组男性比例显著高于正常组[84.62%(33/39)vs 64.28%(27/42);χ^(2)=4.35,P=0.04]。高尿酸组患者的肾脏滤过功能显著低于正常组患者[术后1周CCr:93.67 ml/min vs 135.05 ml/min,术后1个月CCr1:(105.39±40.86)ml/min vs(127.54±55.04)ml/min,术后6个月CCr6:82.64 ml/min vs 99.34 ml/min;P均<0.05]。Logistic多因素回归分析表明术中尿量(OR=1.001,95%CI:1.0002~1.0018,P=0.0176)和肝移植术后1周平均他克莫司全血谷浓度(OR=1.4158,95%CI:1.0256~1.9546,P=0.0346)是肝移植受者发生高尿酸血症的独立危险因素,女性(OR=0.1936,95%CI:0.0368~0.8212,P=0.0482)和肝移植术后第6个月肌酐清除率(OR=0.9059,95%CI:0.8461~0.9698,P=0.0045)为保护性因素。在女性肝移植受者中,高尿酸组患者术后1周平均他克莫司全血谷浓度[(9.51±2.42)ng/ml vs(6.34±2.30)ng/ml]显著高于正常组(P<0.05)。在男性性肝移植受者中,高尿酸组患者CCr6显著低于正常组(82.64 ml/min vs 115.34 ml/min;U=204.00,P<0.001)。Logistic多因素回归分析表明,对于女性肝移植受者,肝移植术后1周平均他克莫司全血谷浓度是发生高尿酸血症的独立危险因素(OR=1.83,95%CI:1.02~3.29,P=0.04),对于男性肝移植受者,术中尿量是发生高尿酸血症的独立危险因素(OR=1.00,95%CI:1.00~1.00,P=0.03),肝移植术后第6个月肌酐清除率(CCr6)为保护性因素(OR=0.94,95%CI:0.89~0.99,P=0.03)。肝移植术后第1周平均他克莫司全血谷浓度(M)M≥7.1 ng/ml的女性患者高尿酸血症发生率显著高于M<7.1 ng/ml女性患者[66.67%(4/6)vs 13.33%(2/15),P=0.03]。结论精细化液体管理,避免容量不足导致的急性肾损伤、维持女性肝移植受者M<7.1 ng/ml可能有助于降低高尿酸血症的发生率,提高肝移植受者生存率和生活质量。

Objective To investigate the risk factors of hyperuricemia after liver transplantation and provide recommendations for preventing hyperuricemia after liver transplantation.Methods Total of 164 liver transplant recipients in Nanjing Drum Tower Hospital,the Affiliated Hospital of Nanjing University Medical School from January 2018 to May 2019 were retrospectively analyzed.The demographic and biochemical data,including gender,age,body mass index,preoperative blood uric acid,duration of liver transplantation operation,intraoperative blood loss,intraoperative urine volume,blood uric acid,average whole blood trough concentration of tacrolimus in the first week after surgery,variation of tacrolimus whole blood trough concentration and creatinine clearance rate(CCr)in the first week,1 month,3 months and 6 months after transplantation were collected.According to the serum uric acid level of 6 months after liver transplantation,the patients were divided into normal group and hyperuricemia group.Multivariate Logistic regression was used to analyze the influencing factors of hyperuricemia in liver transplant recipients.Results A total of 81 patients were eventually enrolled and the incidence of hyperuricemia at 6 months after liver transplantation was 48.15%(39/81).The proportion of male in hyperuricemia group was significantly higher than that in normal group[84.62%(33/39)vs 64.28%(27/42);χ^(2)=4.35,P=0.04].Renal filtration function of patients in hyperuricemia group were significantly lower than those in normal group[1 week after operation CCr:93.67 ml/min vs 135.05 ml/min,1 month after operation CCr1:(105.39±40.86)ml/min vs(127.54±55.04)ml/min,6 month after operation CCr6:82.64 ml/min vs 99.34 ml/min;all P<0.05].Logistic regression showed that the risk factors of hyperuricemia for liver transplantation recipients were intraoperative volume of urine(OR=1.001,95%CI:1.0002~1.0018,P=0.0176)and mean trough concentration of tacrolimus 1 week after liver transplantation(OR=1.4158,95%CI:1.0256~1.9546,P=0.0346),female(OR=0.1936,95%CI:0.0368~0.8212,P=0.0482)and creatinine clearance at the 6 months after liver transplantation(OR=0.9059,95%CI:0.8461~0.9698,P=0.0045)were protective factors.For female liver transplant recipients,the mean trough concentration of tacrolimus of patients in hyperuricemia group was significantly higher than that in normal group at 1 week[(9.51±2.42)ng/ml vs(6.34±2.30)ng/ml;P<0.05].For male liver transplant recipients,CCr6 of patients in hyperuricemia group was significantly lower than those in normal group(82.64 ml/min vs 115.34 ml/min;P<0.05).Logistic regression showed that for female liver transplant recipients,the mean trough concentration of tacrolimus 1 week after liver transplantation was an independent risk factor for hyperuricemia(OR=1.83,95%CI:1.02~3.29,P=0.04).For male liver transplant recipients,intraoperative urine volume was an independent risk factor for hyperuricemia(OR=1.00,95%CI:1.00~1.00,P=0.03)and CCr6 was a protective factor(OR=1.00,95%CI:1.00~1.00,P=0.03).The incidence of hyperuricemia in female patients with M≥7.1 ng/ml was significantly higher than that with M<7.1 ng/ml[66.67%(4/6)vs 13.33%(2/15),P=0.03].Conclusions Precision fluid management to avoid acute kidney injury caused by excessive output and maintaining M<7.1 ng/ml in female liver transplantation recipients may help to reduce the incidence of hyperuricemia and improve the survival rate and quality of life of liver transplantation recipients.