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中华肾病研究电子杂志

中华肾病研究电子杂志 ›› 2020, Vol. 09 ›› Issue (05) : 193 -201. doi: 10.3877/cma.j.issn.2095-3216.2020.05.001

所属专题： 文献；

论著

肝移植术后早期急性肾损伤的危险因素及与预后的关系
白明传1, 邬步云1, 许雪强1, 毛慧娟1,†()   
  1. 1. 210029　南京，南京医科大学第一附属医院（江苏省人民医院）肾内科
  • 收稿日期:2020-04-14 出版日期:2020-10-28
  • 通信作者: 毛慧娟
  • 基金资助:
    国家自然基金面上项目(81970639); 2017年江苏省卫生和健康委员会科研项目(H2017023)

Risk factors and prognosis influence of early acute kidney injury after liver transplantation

Mingchuan Bai1, Buyun Wu1, Xueqiang Xu1, Huijuan Mao1,†()   

  1. 1. Department of Nephrology, First Affiliated Hospital of Nanjing Medical University(Jiangsu Province Hospital), Nanjing 210029, Jiangsu Province, China
  • Received:2020-04-14 Published:2020-10-28
  • Corresponding author: Huijuan Mao
  • About author:
    Corresponding author: Mao Huijuan, Email:
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引用本文：

白明传, 邬步云, 许雪强, 毛慧娟. 肝移植术后早期急性肾损伤的危险因素及与预后的关系[J/OL]. 中华肾病研究电子杂志, 2020, 09(05): 193-201.

Mingchuan Bai, Buyun Wu, Xueqiang Xu, Huijuan Mao. Risk factors and prognosis influence of early acute kidney injury after liver transplantation[J/OL]. Chinese Journal of Kidney Disease Investigation(Electronic Edition), 2020, 09(05): 193-201.

目的

观察肝移植术后患者早期急性肾损伤(acute kidney injury，AKI)的发生情况，探讨其危险因素及预后影响。

方法

回顾性分析2015年10月至2017年11月在南京医科大学第一附属医院肝脏外科进行肝移植术的患者的临床资料。应用改善全球肾脏病预后组织(Kidney Disease: Improving Global Outcomes，KDIGO)2012年修订的AKI诊断和分期标准观察肝移植术后AKI的发生情况，并根据AKI情况将患者分为两组：急性肾损伤和非急性肾损伤组，使用Logistic回归分析患者术后AKI的危险因素。应用Kaplan-Meier生存曲线分析患者术后30 d、90 d及1年的预后。

结果

本研究共纳入146例肝移植患者，术后67例发生AKI(45.9%)，其中AKI 1期占70.1%，AKI 2期占22.4%，AKI 3期占7.5%；其中7例患者接受肾脏替代治疗(renal replacement therapy，RRT)(10.4%)。相比于非AKI患者及AKI 1期的患者，AKI 2～3期患者30 d及90 d生存率明显下降。多因素Logistic回归分析表明，术前血清肌酐(serum creatinine，Scr)升高、国际标准化比值(international normalized ratio，INR)升高、术后天门冬氨酸氨基转移酶(aspartate aminotransferase，AST)升高及术后24 h血红蛋白降低为AKI发生的独立危险因素，并且基于AST峰值评估的肝脏缺血再灌注损伤(hepatic ischemia-reperfusion injury，HIRI)的严重程度与AKI的发生有关。

结论

肝移植术后AKI发生率高，并且与患者短期的预后有关。关注AKI发生的危险因素，有助于进一步采取积极有效的干预措施，对提高肝移植术后预后有着重要的意义。

关键词: 肝移植, 急性肾损伤, 危险因素, 预后
Objective

To observe the occurrence of early acute kidney injury (AKI) in patients after liver transplantation, in order to explore its risk factors and prognostic effects.

Methods

A retrospective analysis was made of the clinical data of patients who underwent liver transplantation at the Department of Liver Surgery, the First Affiliated Hospital of Nanjing Medical University from October 2015 to November 2017. The AKI diagnosis and staging criteria of Kidney Disease: Improving Global Outcomes (KDIGO) in 2012 were used to observe the occurrence of AKI after liver transplantation. The patients were divided into two groups according to the situation of AKI: AKI group and non-AKI group. The risk factors of AKI after operation were analyzed by logistic regression method. Kaplan-Meier survival curve was used to analyze the prognosis of patients of 30 days, 90 days, and 1 year after operation.

Results

A total of 146 patients undergoing liver transplantation were observed, among whom 67 patients presented AKI (45.9%), including AKI stage I (70.1%), stage II (22.4%), and stage Ⅲ (7.5%), and renal replacement therapy (RRT) treatment in 7 patients (10.4%). The 30 day and 90 day survival rates of patients with AKI stage Ⅱ-Ⅲ were significantly lower than those of patients with non-AKI and patients with AKI stage I. Multivariate logistic regression analysis showed that preoperative serum creatinine and international normalized ratio (INR), peak postoperative serum aspartate aminotransferase (AST), and hemoglobin were independent risk factors. And the severity of hepatic ischemia-reperfusion injury (HIRI) based on peak AST was associated with the occurrence of AKI.

Conclusion

The incidence of AKI was high after liver transplantation, which was related to short-term prognosis of the patients. Paying attention to the risk factors of AKI after liver transplantation will help to take further active and effective intervention measures, being of great significance for improving the prognosis of patients after liver transplantation.

Key words: Liver transplantation, Acute kidney injury, Risk factors, Prognosis
表1 肝移植术后AKI和非AKI患者的一般情况
指标 AKI组(n＝67) 非AKI组(n＝79) 统计量值 P值
年龄(岁) 50.46±11.16 48.24±10.73 -1.225 0.222
性别[例(%)]     0.296 0.586
  男性 51(76.12) 57(72.15)    
  女性 16(23.88) 22(27.85)    
体重(kg) 67.75±13.26 63.97±11.27 -1.859 0.065
身高(cm) 169.66±8.14 167.00±7.66 1.652 0.102
BMI(kg/m2) 23.84±3.83 22.58±3.35 1.716 0.089
吸烟[例(%)] 15(22.4) 12(15.2) 1.246 0.264
饮酒[例(%)] 11(16.4) 9(11.4) 0.774 0.379
合并高血压[例(%)] 9(13.4) 7(8.9) 0.777 0.378
合并糖尿病[例(%)] 8(11.9) 6(7.6) 0.759 0.369
Charlson共病评分 3.75±1.42 3.58±1.37 -0.708 0.480
MELD评分 13.94±5.93 11.18±4.37 -3.153 0.002
MELD-Na评分 18.62±6.20 15.28±5.03 -3.231 0.003
原发病[例(%)]     10.564 0.103
  肝硬化 33(49.3) 24(30.4) 0.369 0.985
    肝炎后肝硬化 22(32.8) 16(20.3)    
    胆汁淤积性肝硬化 5(7.5) 3(3.8)    
    酒精性肝硬化 2(3.0) 1(1.3)    
    自身免疫性肝硬化 1(1.5) 1(1.3)    
    原发性肝硬化 3(4.9) 3(3.4)    
  肝细胞性肝癌 26(38.8) 41(51.9)    
  爆发性肝炎 5(7.5) 3(3.8)    
  药物性肝损伤 0(0.0) 2(2.5)    
  胆管细胞癌 1(1.5) 3(3.8)    
  肝豆状核变性 2(3.0) 3(3.8)    
  其他 0(0) 3(3.8)    
预后资料        
  住院天数(d) 28.03±13.50 24.25 -1.477 0.142
  ICU天数(d) 4.31±3.78 2.99±7.62 -1.295 0.197
  出院肌酐(μmol/L) 71.50(52.70，92.30) 63.00(52.50，72.70) -2.687 0.007
表2 AKI和非AKI两组患者术前肾功能等指标的比较
术前指标 AKI组(n＝67) 非AKI组(n＝79) 统计量值 P值
BUN(mmol/L) 5.48±3.66 4.71±1.81 -1.658 0.100
Scr(μmol/L) 67.61±20.84 60.90±16.69 -2.161 0.032
Ccr(ml/min) 115.31±44.46 118.72±32.40 0.534 0.594
eGFR[ml/(min·1.73 m2)] 126.68±39.93 138.24±43.49 1.663 0.099
AST(U/L) 52.05(37.68，100.18) 60.10(37.90，127.90) -0.268 0.789
ALT(U/L) 42.00(25.78，77.33) 51.50(28.20，81.80) -0.542 0.588
PT(s) 18.52±7.21 15.72±4.91 -2.760 0.009
INR 1.59±0.78 1.28±0.55 -2.804 0.008
Hb(g/L) 113.85±23.96 120.27±25.00 1.568 0.119
红血球压积(%) 33.37±9.21 36.19±9.69 1.793 0.075
血小板(×109/L) 82.92±62.94 104.03±94.10 1.554 0.122
收缩压(mmHg) 127.48±14.53 125.66±17.36 0.680 0.498
舒张压(mmHg) 76.06±11.28 77.65±11.53 -0.836 0.404
表3 AKI和非AKI两组患者术中情况比较
术中指标 AKI组(n＝67) 非AKI组(n＝79) 统计量值 P值
手术方式[例(%)]     0.115 0.735
  经典原位式 38(56.7) 47(59.5)    
  改良背驼式 29(43.3) 32(40.5)    
手术时间(min) 420.0(366.0，489.0) 399.0(350.0，480.0) -1.000 0.318
无肝期(min) 63.17±23.73 61.78±20.24 0.256 0.799
出血量(ml) 2200(1200，3200) 1500(1000，2400) -2.646 0.008
出血情况[例(%)]     4.449 0.108
  <1 500 ml 19(28.4) 31(39.2)    
  1 500～3 000 ml 31(47.3) 38(48.1)    
  >3 000 ml 17(18.5) 10(12.7)    
腹水量(ml) 200(0，500) 100(0，800) -1.413 0.158
腹水情况[例(%)]     4.136 0.247
  无 22(32.8) 35(44.3)    
  <1 000 ml 31(46.3) 33(41.8)    
  1 000～2 000 ml 4(6.0) 6(7.6)    
  >2 000 ml 10(14.9) 5(6.3)    
RBC输注量(ml) 1 850(1 200，2 600) 1 600(800，2 400) -2.087 0.037
RBC输注情况[例(%)]     7.076 0.029
  <1 500 ml 19(28.4) 39(49.4)    
  1 500～3 000 ml 37(55.2) 33(41.8)    
  >3 000 ml 11(16.4) 7(8.9)    
血浆输入量(ml) 1 150(800，1 770) 1000(700，1 440) -2.038 0.042
血浆输注情况[例(%)]     6.839 0.077
  <1 000 ml 28(41.8) 42(53.2)    
  1 000～2 000 ml 29(43.3) 34(43.0)    
  >2 000 ml 10(14.9) 3(3.8)    
冷沉淀输入量(ml) 225.0(200，418.75) 225.0(0，250.0) -1.632 0.103
冷沉淀输注情况[例(%)]     4.014 0.134
  <150 ml 15(22.4) 24(30.4)    
  150～300 ml 33(49.3) 43(54.4)    
  >300 ml 19(28.4) 12(15.2)    
表4 AKI组和非AKI组术后相关指标及支持治疗情况
术中指标 AKI组(n＝67) 非AKI组(n＝79) 统计量值 P值
峰值AST (U/L) 1907(808，3397) 1100(638，2178) -3.097 0.002
峰值ALT(U/L) 837(486，1742) 564(335，1082) -2.429 0.015
总胆红素(μmol/L) 77.50(51.60，114.25) 62.15(45.15，95.33) -1.157 0.247
直接胆红素(μmol/L) 52.40(35.00，78.35) 43.00(27.03，54.13) -1.920 0.055
胆固醇(mmol/L) 2.06±0.74 2.21±0.73 1.254 0.212
血清白蛋白(g/L) 36.43±6.15 38.40±5.39 2.049 0.042
初次动脉血气分析        
  PaO2 (mmHg) 201.0(148.0，265.0) 197.5(153.5，257.5) -0.624 0.533
  PaCO2 (mmHg) 38.40±6.95 38.09±5.63 -0.293 0.770
  pH 7.41±0.07 7.42±0.07 -1.196 0.234
  Lac 2.90(1.70，4.15) 2.55(1.63，4.18) -0.780 0.436
  BE -0.43±3.86 0.32±3.38 -1.189 0.237
  Hct% 29.00(26.00，32.50) 30.00(28.00，33.00) -1.421 0.155
收缩压(mmHg) 115.3±19.6 118.2±16.2 0.972 0.333
舒张压(mmHg) 65.8±12.8 65.9±11.1 -0.071 0.944
利尿剂[例(%)]     5.844 0.016
  未用 29(43.3) 50(63.3)    
  使用 38(56.7) 29(36.7)    
血管活性药物[例(%)]     5.214 0.022
  未用 41(61.2) 62(78.5)    
  使用 26(38.8) 17(21.5)    
qSOFA评分 1(0.0，2.0) 2(0.0，3.0) -1.998 0.046
机械通气时间[例(%)]     12.744 0.002
  <12 h 7(10.5) 21(26.6)    
  12～24 h 21(31.3) 34(43.0)    
  >24 h 39(58.2) 24(30.4)    
表5 AKI和非AKI两组术后3 d内相关指标及出入量情况
术后指标 AKI组(n＝67) 非AKI组(n＝79) 统计量值 P值
Scr(μmol/L)        
  24 h Scr 117.7±54.0 64.3±17.3 -8.017 <0.001
  48 h Scr 125.0±84.9 60.8±17.1 -7.766 <0.001
  72 h Scr 119.7±82.8 56.9±15.0 -8.004 <0.001
Hb(g/L)        
  24 h Hb 104.0(93.0，111.5) 107.0(97.0，134.0) 2.956 0.004
  48 h Hb 99.6±18.4 109.5±16.3 3.405 0.001
  72 h Hb 101.9±20.0 110.4±15.9 2.861 0.005
出入量(ml)        
  24 h尿量 1 330(830，2 087) 2 040(1 370，2 553) -5.505 <0.001
  48 h尿量 2 337±1 067 2 455±996 0.686 0.494
  72 h尿量 2 383±1 281 2 846±1 181 2.265 0.025
  24 h引流量 180(55，550) 180(42，465) -0.659 0.510
  48 h引流量 260(140，705) 190(20，640) -1.292 0.196
  72 h引流量 210(75，460) 210(15，605) -0.060 0.952
  24 h入量 2 512±1 279 2 773±1 019 0.108 0.172
  48 h入量 3 624(3 106，4 129) 3 180(2 756，3 677) -3.055 0.002
  72 h入量 3 257(2 960，3 919) 3 576 (2 756，3 677) -0.740 0.460
表6 AKI危险因素的多因素Logistic回归分析
变量 B值 OR值 95%CI P值
术前Scr (μmol/L) 0.028 1.029 1.007，1.050 0.009
术前INR 1.018 2.769 1.186，6.466 0.019
术后AST峰值(U/L) 0.000 1.000 1.000，1.001 0.002
术后24 h Hb (g/L) -0.028 0.972 0.950，0.994 0.014
表7 AKI危险因素的预测价值
指标 Cutoff值 敏感性(%) 特异性(%) AUC 95%CI P值
术前Scr (μmol/L) 55.15 76.1 51.9 0.602 0.510，0.694 0.034
术前INR 1.45 50.2 74.7 0.612 0.519，0.706 0.020
术后峰值AST(U/L) 3 044 35.8 91.1 0.649 0.558，0.740 0.002
术后24 h Hb (g/L) 112.5 77.6 43.0 0.621 0.530，0.712 0.012
联合预测 - 72.7 71.9 0.760 0.680，0.839 <0.001
图1 非AKI、AKI 1期与AKI 2～3期患者30 d、90 d及1年生存分析
表8 近5年研究中肝移植术后AKI发生的影响因素
作者 年份 研究人数 影响因素
Wyssusek等[16] 2015 97 BMI、MELD评分、术中去甲肾上腺素使用
Yoo等[17] 2016 304 男性、肺动脉高压、高血压
Zhou等[18] 2017 103 BMI、尿量、手术时间、术后血管加压素使用
Chen等[19] 2017 566 无肝期时间、术中高收缩压
Yin等[20] 2017 5 074 术前血清肌酐、术中失血、冷热缺血时间、多巴胺使用、CNIs暴露
Gomes等[21] 2018 400 术前碱性磷酸酶、直接胆红素、γ-谷氨酰转移酶和血清白蛋白水平
Cheng等[22] 2018 321 术前肝硬化、MELD评分、术中红细胞输注量
Chae等[23] 2018 272 术中血清脑钠肽水平、术中红细胞输注量、肝脏总缺血时间
张达利等[24] 2019 469 受体BMI、术前肌酐水平、阻断下腔静脉时间、手术时间、术后乳酸峰值、术后AST峰值
李喆等[25] 2020 301 无肝期时间、术中应用2种以上的血管活性药物
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