中华急诊医学杂志  2021, Vol. 30 Issue (7): 848-855   DOI: 10.3760/cma.j.issn.1671-0282.2021.07.010
接受不同他汀治疗的冠状动脉旁路移植术后发生急性肾损伤的影响因素分析
庞广辉1 , 田阳2 , 欧知宏3 , 张秀辉1 , 周忠启4 , 李俊生5 , 李峥嵘5     
1. 山东大学附属临沂市人民医院心脏血管外科 276003;
2. 兰陵县人民医院胸心外科 277799;
3. 山东大学附属临沂市人民医院心血管内科 276003;
4. 山东大学附属临沂市人民医院肾内科 276003;
5. 山东大学附属临沂市人民医院药学部 276003
摘要: 目的 对比研究瑞舒伐他汀和阿托伐他汀对冠状动脉旁路移植术(coronary artery bypass grafting,CABG)患者急性肾损伤(acute kidney injury,AKI)发生的影响,并分析CABG术后AKI的影响因素。方法 回顾性收集2014年5月至2020年5月年龄大于18周岁、在山东大学附属临沂市人民医院心脏外科接受CABG术的550例患者为研究对象。根据患者术前是否常规应用瑞舒伐他汀或阿托伐他汀分为瑞舒伐他汀组(n=322)、阿托伐他汀组(n=125)和非他汀组(n=103)。收集患者的人口统计学资料、CABG前后的临床资料和实验室检查结果。比较三组患者的尿素氮(blood urea nitrogen,BUN)、血清肌酐(serum creatinine,Scr)、肌酐清除率(creatinine clearance rate,Ccr)以及术后AKI发生情况; 采用单因素分析和二分类Logistic回归分析探讨他汀对CABG术患者发生AKI的影响。结果 与术前相比,550例患者术后BUN差异无统计学意义(P > 0.05),Scr升高,Ccr降低,差异均有统计学意义(P < 0.01)。瑞舒伐他汀组术后BUN降低,差异有统计学意义(P < 0.01),Scr、Ccr无显著变化(P > 0.05);阿托伐他汀组术后Scr升高,差异有统计学意义(P < 0.01),BUN、Ccr差异无统计学意义(P > 0.05);非他汀组术后BUN、Scr升高,Ccr降低,差异均有统计学意义(P < 0.01)。瑞舒伐他汀组和阿托伐他汀组术后BUN、Scr均低于非他汀组,差异均有统计学意义(均P < 0.01);Ccr高于非他汀组,差异有统计学意义(P < 0.01)。瑞舒伐他汀组BUN、Scr和阿托伐他汀组差异均无统计学意义(P > 0.05),Ccr高于阿托伐他汀组,差异有统计学意义(P < 0.05)。三组间BUN、Scr、Ccr差异有统计学意义(χ2值分别为48.925、22.677、34.426,均P < 0.01)。550例患者中AKI发生率为15.1%(83/550),其中瑞舒伐他汀组9.6%(31/322),阿托伐他汀组16.0%(20/125),非他汀组31.1%(32/103)。瑞舒伐他汀组和阿托伐他汀组AKI发生率均低于非他汀组,差异有统计学意义(χ2值分别为28.412、7.282,P < 0.01)。多因素回归分析发现高血压病史(OR=3.555,95%CI:1.959~6.451,P < 0.01)、NHYA心功能Ⅲ/Ⅳ(OR=2.438,95%CI:1.187~5.008,P=0.015)、血清肌酐水平升高(OR=1.018,95%CI:1.003~1.032,P=0.016)、术中采用体外循环(OR=2.936,95%CI:1.454~5.927,P=0.003)是CABG术后发生AKI的独立危险因素; 而术前常规他汀治疗(OR=0.490,95%CI:0.247~0.974,P=0.042)和血清白蛋白水平(OR=0.920,95%CI:0.856~0.990,P=0.026)是CABG术后发生AKI的保护因素。结论 CABG术后发生AKI常见,术前常规应用瑞舒伐他汀或阿托伐他汀以及术前高血清白蛋白水平均可以保护肾功能,降低术后AKI发生率,是CABG术后AKI的保护因素,而高血压病史、NHYA心功能Ⅲ/Ⅳ、术前血清肌酐水平升高、术中采用体外循环是CABG术后发生AKI的独立危险因素。
关键词: 瑞舒伐他汀    阿托伐他汀    冠状动脉旁路移植    急性肾损伤    
Analysis of influencing factors of acute kidney injury in coronary artery bypass grafting patients treated with different statins
Pang Guanghui1 , Tian Yang2 , Ou Zhihong3 , Zhang Xiuhui1 , Zhou Zhongqi4 , Li Junsheng5 , Li Zhengrong5     
1. Department of Cardiovascular Surgery, Linyi People's Hospital, Shandong University, Linyi 276003, China;
2. Department of Cardiothoracic Surgery, Lanling People's Hospital, Lanling, 277799, China;
3. Department of Cardiology, Linyi People's Hospital, Shandong University, Linyi 276003, China;
4. Department of Nephrology, Linyi People's Hospital, Shandong University, Linyi 276003, China;
5. Department of Pharmacy, Linyi People's Hospital, Shandong University, Linyi 276003, China
Abstract: Objective To compare the effects of rosuvastatin and atorvastatin on coronary artery bypass grafting (CABG) on the incidence of acute kidney injury (AKI), and assess the independent risk factors of AKI. Methods We retrospectively collected 550 patients aged 18 years or older who underwent CABG from May 2014 to May 2020. They were divided into the rosuvastatin group (n=322), atorvastatin group (n=125) and non statins group (n=103) according to whether rosuvastatin or atorvastatin was routinely used before operation. Demographic data, clinical data before and after CABG and laboratory results were collected. Blood urea nitrogen (BUN), serum creatinine (Scr), creatinine clearance rate (Ccr) and incidence of postoperative AKI were compared among the three groups. Univariate analysis and binary logistic regression analysis were used to investigate the effect of statins on AKI in patients undergoing CABG. Results Compared with preoperation, BUN showed no significant change (P > 0.05), while Scr was increased and Ccr was decreased significantly (both P < 0.01); BUN in the rosuvastatin group was decreased significantly (P < 0.01), whereas Scr and Ccr had no significant change (P > 0.05); Scr in the atorvastatin group was increased significantly (P < 0.01), but there was no significant difference in BUN and Ccr (P > 0.05). BUN and Scr in the non statins group were increased significantly (both P < 0.01), while Ccr was decreased significantly (P < 0.01). After operation, BUN and Scr in the rosuvastatin group and atorvastatin group were significantly lower than those in the non statins group (all P < 0.01); Ccr was significantly higher than that in the non statins group (P < 0.01). BUN and Scr were not significantly different between the rosuvastatin and atorvastatin groups (P > 0.05), but Ccr was significantly higher than that in the atorvastatin group (P < 0.05). There were significant differences in BUN, Scr and Ccr among the three groups (χ2=48.925, 22.677 and 34.426, all P < 0.01). The incidence of AKI among 550 patients was 15.1% (83/550), of which 9.6% (31/322) in the rosuvastatin group, 16.0% (20/125) in the atorvastatin group and 31.1% (32/103) in the non statins group. The incidence of AKI in the rosuvastatin and atorvastatin groups was significantly lower than that in the non statins group (χ2=28.412, 7.282, P < 0.01). Multivariate regression analysis showed that hypertension (OR=3.555, 95%CI: 1.959-6.451, P < 0.01), NHYAⅢ/Ⅳ (OR=2.438, 95%CI: 1.187-5.008, P=0.015), and increased serum creatinine level (OR=1.018, 95%CI: 1.003-1.032, P=0.016), and intraoperative cardiopulmonary bypass (OR=2.936, 95%CI: 1.454-5.927, P=0.003) were independent risk factors for AKI after CABG, while preoperative conventional statin therapy (OR=0.490, 95%CI: 0.247-0.974, P=0.042) and increased serum albumin level (OR=0.920, 95%CI: 0.856-0.990, P=0.026) were protective factors for AKI after CABG. Conclusions The incidence of AKI after CABG is common. Rosuvastatin or atorvastatin and increased preoperative serum albumin level can protect renal function and reduce the incidence of AKI, which are the protective factors of AKI after CABG. The hypertension, NHYAⅢ/Ⅳ, increased preoperative serum creatinine level and cardiopulmonary bypass are the independent risk factors of AKI after CABG.
Key words: Rosuvastatin    Atorvastatin    Coronary artery bypass grafting    Acute kidney injury    

心脏手术相关性急性肾损伤(cardiac surgery­-associated acute kidney injury,CSA-AKI)是指发生在心脏外科术后的急性肾功能损害,是冠状动脉旁路移植术(coronary artery bypass grafting,CABG)术后常见而严重的并发症,不但显著延长患者滞留ICU时间和住院时间[1]、显著增加患者住院费用[2],而且显著增加患者死亡风险[2-3]。因此,早期预防并降低CABG术后急性肾损伤(acute kidney injury,AKI)的发生对降低CABG术后病死率极为重要。

他汀类药物凭借其降脂和独立于降脂作用外的抗炎、抗氧化、改善血管功能等作用被认为具有肾脏保护作用[4-5]。笔者前期研究也显示,对于行CABG的患者,术前常规应用瑞舒伐他汀可保护肾功能,降低术后AKI发生率[6]。但不同种类的他汀对CABG患者术后AKI的影响是否一致尚不明确。本研究回顾性分析CABG患者围手术期的临床资料,分析阿托伐他汀或瑞舒伐他汀对CABG患者围手术期AKI的影响并对AKI的影响因素进行分析,以期对CABG术后AKI的防治提供依据。

1 资料与方法 1.1 一般资料

纳入2014年5月至2020年5月在山东大学附属临沂市人民医院心外科住院治疗并行CABG的成年冠心病患者进行回顾性队列研究。排除标准:⑴年龄 < 18岁; ⑵估算术前肾小球滤过率 < 30 mL/min; ⑶CABG术后48 h内和术前缺失至少一次血清肌酐(serum creatinine,Scr)值; ⑷合并其他心脏手术; ⑸住院期间曾服用阿托伐他汀和瑞舒伐他汀之外的其他他汀类药物; ⑹术后住院时间 < 48 h或术后48 h内死亡; ⑺术前有严重肝功能不全病史; ⑻终末期肾脏疾病或肾脏移植患者; ⑼病史资料不完整。

本研究共纳入550例行CABG治疗患者。本研究由临沂市人民医院医学科学伦理委员会批准(医学伦审第YX30062号)。

1.2 研究分组与数据收集

根据患者术前是否服用他汀类药物和他汀类药物种类分为阿托伐他汀组、瑞舒伐他汀组和非他汀组,阿托伐他汀组患者术前常规服用阿托伐他汀20 mg/次,1次/d,时间≥5 d,并持续应用至术后时间≥48 h; 瑞舒伐他汀组患者术前常规服用瑞舒伐他汀10 mg/次,1次/d,时间≥5 d,并持续应用至术后时间≥48 h; 非他汀组患者术前未服用他汀或停用他汀时间≥5 d,术后48 h内未服用任何他汀类药物。

收集患者的各项资料,包括临床特征:性别、年龄、体质量、合并症、纽约心脏协会(NHYA)心功能分级、手术情况、围手术期用药等; 实验室资料:术前血清尿素氮、Scr、甘油三酯、总胆固醇、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、空腹血糖水平、血清白蛋白水平等。

根据Cockcroft-Gault公式估算两组患者术前及术后肌酐清除率(Ccr)。

1.3 AKI诊断标准

根据AKIN的标准,将AKI定义为48 h内Scr上升≥26.4 μmol/L,或较基础值增加≥50%和(或)尿量 < 0.5 mL/(kg·h)达6 h[7]。以术前最近一次Scr水平为基线值; 以患者术后48 h内Scr水平为术后Scr值,如有多次结果则取最高值。

1.4 统计学方法

采用SPSS 20.0软件进行数据统计分析。计量资料先进行正态性检验,符合正态分布用均数±标准差(Mean±SD)表示,组间比较采用独立样本t检验; 非正态分布用中位数(四分位数)[M(QL, QU)]表示,组间比较采用Mann-Whitney U检验。计数资料采用频数(百分率或构成比)表示,组间比较采用χ2检验或Fisher精确概率检验。CABG术后AKI的危险因素经单因素分析后,单因素分析中P < 0.05的指标纳入二分类Logistic回归分析(Eenter法)。以P < 0.05为差异有统计学意义。

2 结果 2.1 研究对象基本特征

550例CABG术患者中,年龄为65.0岁(59.0,69.0)岁,最大85岁,最小40岁; 其中男性397例(72.2%),女性153例(27.8%); 合并症由高到低依次为高血压病277例(50.4%)、心肌梗死199例(36.2%)、糖尿病158例(28.7%)、NHYA心功能Ⅲ/Ⅳ 57例(10.4%)、脑梗死49例(8.9%)。基线血清尿素氮为5.1(4.3,6.4)mmol/L,血清肌酐为67.5(57.1,77.8)μmol/L,基线Ccr为90.4(72.7,108.7)mL/min。见表 1

表 1 三组患者临床资料比较 Table 1 Comparison of the general characteristics of patients among the three groups
指标 总计(n=550) 瑞舒伐他汀组(n=322) 阿托伐他汀组(n=125) 非他汀组(n=103) χ2/F P
年龄(岁)a 65.0(59.0, 69.0) 64.5(58.0, 69.0) 66.0(61.5, 70.0) 64.0(58.0, 69.0) 6.822 0.033
男/女 397/153 239/83 95/30 63/40 7.802 0.020
体质量(kg)a 67.0(60.0,75.0) 68.0(62.0, 75.0) 67.0(60.0, 75.0) 65.0(55.0, 70.0) 11.800 0.003
吸烟史(例,%) 362(65.8) 210(65.2) 87(69.6) 65(63.1) 1.183 0.554
饮酒史(例,%) 371(67.5) 219(68.0) 83(66.4) 69(67.0) 0.119 0.942
术前生化指标
  BUN(mmol/L)a 5.1(4.3, 6.4) 5.1(4.2, 6.3) 4.9(4.2, 6.1) 5.8(4.7, 7.4) 16.066 < 0.01
  Scr(μmol/L)a 67.5(57.1, 77.8) 67.0(57.0, 76.3) 67.6(57.9, 77.8) 69.4(56.9, 82.7) 1.462 0.481
  Ccr(mL/min)a 90.4(72.7, 108.7) 93.6(75.4, 111.7) 86.9(74.1, 105.4) 82.8(65.8, 104.7) 11.829 0.003
  TG(mmol/L)a 1.3(0.9, 1.8) 1.3(1.0, 1.8) 1.2(0.9, 1.8) 1.2(0.8, 1.7) 6.239 0.044
  CHO(mmol/L)b 4.2(3.6, 5.0) 4.3±1.0 4.4±1.1 4.3±1.1 2.980 0.052
  HDL-C(mmol/L)a 1.0(0.9, 1.2) 1.0(0.9, 1.1) 1.0(0.9, 1.2) 1.1(0.9, 1.4) 18.611 < 0.01
  LDL-C(mmol/L)b 2.6(2.1, 3.2) 2.7±0.8 2.6±0.8 2.8±0.8 1.326 0.266
  空腹血糖(mmol/L)a 5.4(4.9, 6.6) 5.5(4.9, 6.6) 5.6(5.0, 7.5) 5.2(4.6, 5.9) 14.540 0.001
  尿酸(mmol/L)a 322.8(271.8, 391.7) 325.7(275.5, 385.5) 304.6(267.0, 372.2) 335.0(277.0, 427.0) 6.424 0.040
  血清白蛋白(g/L)b 38.5±3.6 38.9±3.6 37.5±3.5 38.5±3.6 6.803 0.001
合并疾病(例,%)
  高血压病 277(50.4) 169(52.5) 72(57.6) 36(35.0) 12.985 0.002
  心肌梗死 199(36.2) 132(41.0) 55(44.0) 12(11.7) 33.382 < 0.01
  糖尿病 158(28.7) 101(31.4) 38(30.4) 19(18.4) 6.583 0.037
  脑梗死 49(8.9) 31(9.6) 13(10.4) 5(4.0) 2.634 0.268
NHYA心功能Ⅲ/Ⅳ(例,%) 57(10.4) 21(6.5) 12(9.6) 24(19.2) 23.753 < 0.01
术前1周内血管造影(例,%) 205(37.3) 64(19.9) 40(32.0) 37(29.6) 13.976 0.001
术前用药(例,%)
  ACEI/ARB 219(39.8) 129(40.1) 55(44.0) 35(34.0) 2.385 0.303
  钙拮抗剂 168(30.5) 99(30.7) 41(32.8) 28(27.2) 0.854 0.652
  利尿剂 202(36.7) 119(37.0) 44(35.2) 39(37.9) 0.190 0.909
  胰岛素 95(17.3) 58(18.0) 21(16.8) 16(15.5) 0.361 0.835
术中情况
  桥血管数量(支)a 4.0(3.0, 4.0) 4.0(3.0, 4.0) 3.0(3.0, 4.0) 4.0(3.0, 4.0) 10.563 0.005
  术中失血(mL)a 350.0(300.0, 400.0) 350.0(300.0, 400.0) 300.0(275.0, 400.0) 400.0(300.0, 400.0) 10.955 0.004
  手术持续时间(h)a 3.5(3.0, 4.0) 3.5(3.0, 4.0) 3.5(3.0, 4.0) 4.0(3.5, 4.5) 12.576 0.002
  体外循环(例,%) 128(23.3) 51(15.8) 19(15.2) 58(56.3) 77.488 < 0.01
  呼吸机时间 > 24 h(例,%) 229(41.6) 128(39.8) 53(42.4) 48(46.6) 1.546 0.462
术后早期用药(例,%)
  血管活性药物≥3种 233(42.4) 135(41.9) 51(40.8) 47(45.6) 0.601 0.741
  洋地黄类药物 123(22.4) 67(20.8) 30(24.0) 26(25.2) 1.134 0.567
  利尿剂 433(78.7) 251(78.0) 99(79.2) 83(80.6) 0.344 0.842
  ACEI/ARB 114(20.7) 64(20.0) 26(20.8) 24(23.3) 0.558 0.757
注:BUN为血清尿素氮; Scr为血清肌酐; Ccr为肌酐清除率; TG为甘油三酯; CHO为总胆固醇; HDL-C为高密度脂蛋白胆固醇; LDL-C为低密度脂蛋白胆固醇; NHYA为纽约心脏协会; ACEI为血管紧张素转换酶抑制剂; ARB为血管紧张素Ⅱ受体拮抗剂。aM(QL, QU); b为Mean±SD

术后48 h内共有83例(15.1%)患者发生AKI。

2.2 3组患者围手术期肾功能变化分析比较

与术前比较,550例患者术后BUN无显著变化(Z=-0.445,P=0.657),Scr升高,差异有统计学意义(Z=-5.066,P < 0.01),Ccr降低,差异有统计学意义(Z=-3.137,P < 0.01)。瑞舒伐他汀组BUN降低,差异有统计学意义(Z=-2.988,P=0.003),Scr和Ccr均降低,但差异均无统计学意义(Z值分别为1.535、-0.044,P=0.125、0.965)。术后阿托伐他汀组BUN升高,差异无统计学意义(Z =1.013,P=0.311),Scr升高,差异有统计学意义(Z=2.645,P=0.008),Ccr降低,但差异无统计学意义(Z=-1.757,P=0.079)。非他汀组BUN、Scr升高,差异均有统计学意义(Z 值分别为4.279、5.231,P < 0.01),Ccr降低,差异有统计学意义(Z =-4.810,P < 0.01)。见表 2

表 2 3组患者围手术期肾功能变化比较[M(QL, QU)] Table 2 Comparison of the changes in renal function among the three groups [M(QL, QU)]
组别 BUN(mmol/L) Scr(μmol/L) Ccr(mL/min)
瑞舒伐他汀组(n=322)
  术前 5.1(4.2, 6.3) 67.0(57.0, 76.3) 93.6(75.4, 111.7)
  术后 4.6(3.7, 6.0)ab 66.8(53.5, 82.0)b 92.1(71.0, 112.4)bc
阿托伐他汀组(n=125)
  术前 4.9(4.2, 6.1) 67.6(57.9, 77.8) 86.9(74.1, 105.4)
  术后 4.8(4.0, 6.7)b 68.4(57.8, 83.6)ab 86.3(64.2, 106.2)b
非他汀组(n=103)
  术前 5.8(4.7, 7.4) 69.4(56.9, 82.7) 82.8(65.8, 104.7)
  术后 7.0(4.8, 9.7)a 77.5(61.0, 114.7)a 70.3(45.2, 93.5)a
总计(n=550)
  术前 5.1(4.3, 6.4) 67.5(57.1, 77.8) 90.4(72.7, 108.7)
  术后 4.9(3.9, 6.9) 68.5(56.1, 85.1)a 87.4(65.2, 109.0)a
注:BUN为血清尿素氮; Scr为血清肌酐; Ccr为肌酐清除率; 组内与术前比较,aP < 0.05;与非他汀组比较,bP < 0.05;与阿托伐他汀组比较,cP < 0.05

术后,瑞舒伐他汀组BUN、Scr均低于非他汀组,差异均有统计学意义(Z值分别为-6.904、-4.701,均P < 0.01),Ccr高于非他汀组,差异有统计学意义(Z=-5.759,P < 0.01);阿托伐他汀组BUN、Scr均低于非他汀组,差异均有统计学意义(Z值分别为- 4.959、- 3.116,均P < 0.01);Ccr高于非他汀组,差异有统计学意义(Z=-3.464,P=0.001);瑞舒伐他汀组BUN低于阿托伐他汀组,差异无统计学意义(Z=-1.519,P=0.129),Scr低于阿托伐他汀组,差异无统计学意义(Z=-1.390,P=0.165),Ccr高于阿托伐他汀组,差异有统计学意义(Z=-2.164,P=0.030)。三组间BUN、Scr、Ccr差异有统计学意义(χ2值分别为48.925、22.677、34.426,均P < 0.01)。见表 2

2.3 3组患者术后AKI发生情况分析比较

550例患者中有83例术后发生AKI,总体AKI发生率为15.1%(83/550)。瑞舒伐他汀组患者术后AKI发生率为9.6%(31/322),阿托伐他汀组患者术后AKI发生率为16.0%(20/125),非他汀组患者术后AKI发生率为31.1%(32/103)。瑞舒伐他汀组和阿托伐他汀组AKI发生率均低于非他汀组,差异有统计学意义(χ2值分别为28.412、7.282,P < 0.01);瑞舒伐他汀组AKI发生率低于阿托伐他汀组,但差异无统计学意义(χ2=3.618,P=0.057);三组间AKI发生率比较差异有统计学意义(χ2=28.101,P < 0.01)。

2.4 CABG术后AKI的影响因素

单因素logistic分析发现,合并高血压病、心肌梗死病史、NHYA心功能Ⅲ/Ⅳ,术前血清尿素氮、血清肌酐、血尿酸、血清白蛋白,手术时间、术中失血量、桥血管数量、体外循环、使用他汀等是CABG术后AKI的影响因素(均P < 0.05),见表 3

表 3 冠状动脉旁路移植术患者术后发生AKI的单因素回归分析 Table 3 Univariate regression analysis of AKI in patients after coronary artery bypass grafting
因素 OR 95%CI P
性别 0.994 0.590~1.674 0.981
年龄 0.996 0.966~1.027 0.809
体质量 0.996 0.975~1.017 0.709
高血压病 2.037 1.253~3.314 0.004
糖尿病 1.407 0.858~2.308 0.176
NHYA心功能Ⅲ/Ⅳ 3.689 2.015~6.755 < 0.01
心肌梗死 0.511 0.299~0.873 0.014
使用他汀类药物 0.286 0.172~0.475 < 0.01
体外循环 4.185 2.579~6.791 < 0.01
1周内造影史 1.134 0.671~1.915 0.639
血清尿酸 1.003 1.001~1.006 0.004
空腹血糖 1.008 0.913~1.114 0.870
血尿素氮 1.259 1.134~1.398 < 0.01
血清肌酐 1.026 1.015~1.037 < 0.01
血清白蛋白 0.935 0.876~0.998 0.044
高密度脂蛋白胆固醇 1.880 0.831~4.253 0.129
术中失血量 1.004 1.002~1.005 < 0.01
手术时间 1.435 1.102~1.869 0.007
桥血管数量 1.557 1.137~2.131 0.006

多因素回归分析发现高血压病(OR=3.555,95%CI:1.959~6.451,P < 0.01)、NHYA心功能Ⅲ/Ⅳ(OR=2.438,95%CI:1.187~5.008,P=0.015)、血清肌酐(OR=1.018,95%CI:1.003~1.032,P=0.016)、体外循环(OR=2.936,95%CI:1.454~5.927,P=0.003)是CABG术后发生AKI的独立危险因素; 而使用他汀(OR=0.490,95%CI:0.247~0.974,P=0.042)和血清白蛋白(OR=0.920,95%CI:0.856~0.990,P=0.026)是CABG术后AKI的保护因素,见表 4

表 4 冠状动脉旁路移植术患者术后AKI的多因素回归分析 Table 4 Multivariate regression analysis of AKI in patients after coronary artery bypass grafting
因素 B SE OR 95%CI χ2 P
高血压病 1.268 0.304 3.555 1.959~6.451 17.408 < 0.01
NHYA心功能Ⅲ/Ⅳ 0.891 0.367 2.438 1.187~5.008 5.883 0.015
心肌梗死 -0.332 0.326 0.717 0.379~1.358 1.042 0.307
使用他汀 -0.713 0.350 0.490 0.247~0.974 4.416 0.042
体外循环 1.077 0.358 2.936 1.454~5.927 9.026 0.003
血清尿酸 0.001 0.001 1.001 0.998~1.004 0.627 0.428
血尿素氮 0.039 0.075 1.039 0.897~1.204 0.262 0.608
血清肌酐 0.017 0.007 1.018 1.003~1.032 5.781 0.016
血清白蛋白 -0.083 0.037 0.920 0.856~0.990 4.988 0.026
术中失血量 0.001 0.001 1.001 0.998~1.004 0.538 0.463
手术时间 -0.107 0.197 0.899 0.611~1.323 0.292 0.589
桥血管数量 0.210 0.201 1.233 0.832~1.829 1.088 0.297
3 讨论

AKI是临床常见的肾脏急危重症,是心脏外科术后死亡的独立危险因素之一[8],近年来AKI已成为全球关注的公共卫生问题[9]。由于AKI定义标准及所选择患者人种、手术方式等因素的差异,文献报道的CABG术后AKI的发生率有所差异。近几年国内外的一些研究结果显示,CABG术后AKI发生率在5.7%~39%[3, 10-18],本研究中应用AKIN的AKI标准,CABG术后AKI的总体发生率为15.1%。

CSA-AKI的发生机制复杂,目前尚不十分明确,目前国内外学者普遍认为肾脏低灌注所致的缺血性肾小管(特别是近端小管)损伤和坏死是肾损伤最常见原因[19],而在AKI发生过程中,炎症和血管内皮功能障碍的激活起着至关重要的作用[20],他汀类药物通过抑制胆固醇合成、抗炎和抗氧化的多效性成为心脑血管疾病治疗的基石,可以明显改善相关疾病的预后。多项随机对照研究和Meta分析均显示,术前应用他汀治疗可以减少经皮冠状动脉造影术后的AKI[21-24],但目前术前常规他汀治疗对CABG围手术期AKI的影响还存在争议,相关研究结果并不一致[6, 10, 15, 20, 25-27]

本研究通过对550例行CABG术患者围手术期肾功能水平变化的回顾性分析发现,与术前比较,不论术前是否常规应用他汀类药物治疗,CABG患者术后普遍存在肾功能的降低,但术前常规瑞舒伐他汀或者阿托伐他汀治疗会延缓患者CABG术后肾功能下降趋势,显著降低围手术期AKI发生率。这与笔者之前的研究结果一致[6]。Layton等[10, 15]的两项回顾性调查分析也显示术前开始使用他汀类药物可以降低CABG术后AKI风险。但也有一些研究得到了不同的结果,来自中国医学科学院阜外医院的一项随机、对照、双盲研究[25]发现心脏外科围手术期使用他汀类药物,不但未能保护患者肾功能,反而使患者AKI发生率显著增加。一篇纳入18项随机对照研究的Meta分析也显示,围手术期使用他汀药物不能降低心脏手术后AKI风险[26],而且对于瓣膜置换术患者AKI有增加趋势。而一篇纳入18项研究涉及32 747例患者的Meta分析发现,CABG术前他汀类药物治疗虽然无法降低术后AKI风险,但是可以降低围手术期肾功能不全和术后肾脏替代治疗的风险[27]。Singh等[20]的Meta分析也显示,CABG术前他汀类药物治疗虽然对AKI发生率没有影响,但是可以显著降低术后肾脏替代治疗的发生率。不同研究结果的差异可能和不同的研究纳入的患者人种、年龄、术前肾脏功能、手术类型、AKI标准以及选用他汀类药物种类不同有关。

本研究发现高血压病、NHYA心功能Ⅲ/Ⅳ、术前血清肌酐水平升高、术中体外循环是CABG术后发生AKI的独立危险因素; 而围手术期常规使用他汀和术前高白蛋白水平是CABG术后AKI的保护因素。Hiew等[3]对1 260例单纯CABG术患者进行研究,发现年龄、胰岛素依赖型糖尿病、基线血清肌酐水平、近期心肌梗死、体外循环时间是AKI的独立危险因素。Barkhordari等[17]也证实年龄越大,体质量指数越高,术前肌酐水平越低,ICU输血越多,术中输血不足,体外循环时间越长是CABG患者发生AKI的危险因素。这也提示,临床在寻找降低CABG术后AKI风险策略的时候,应该对CABG后AKI的高危患者严格进行术前评估、围术期保护及严密监测肾功能,最大程度地降低CABG后AKI发生的风险。

本研究存在许多不足之处:⑴本研究为单中心的回顾性研究,样本量小,可能会使研究结果产生偏倚; ⑵他汀是目前冠心病治疗的基础药物,CABG术前未给予常规他汀治疗的患者在实际临床治疗过程中并不多见,致使非他汀组相对他汀治疗组患者较少,可能会对研究结果产生影响; ⑶本研究中三组患者年龄、男女比例、体质量、术前BUN、术前Ccr、术前1周内血管造影史、合并症、术中失血、手术持续时间等存在明显差异,可能对研究结果产生影响。

综上所述,本研究结果表明,CABG患者术前常规服用瑞舒伐他汀或阿托伐他汀,均可以保护患者肾功能,显著降低患者术后AKI发生率,围手术期常规使用他汀和术前血清白蛋白水平升高是CABG术后AKI的保护因素; 而高血压病、NHYA心功能Ⅲ/Ⅳ、术前血清肌酐水平升高、术中体外循环是CABG术后发生AKI的独立危险因素。考虑到本研究尚存在不足之处,下一步需要开展多中心随机对照试验来进一步证实他汀类药物对CABG术后AKI的影响,同时深入研究CABG术后发生AKI的危险因素,寻找降低CABG后AKI风险的综合防治策略。

利益冲突   所有作者均声明不存在利益冲突

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