普罗布考预防对比剂肾损害的随机化临床研究

目的 对比剂诱导的急性肾损害(contrast induced acute kidney injury,CIAKI)是医源性急性肾功能衰竭的主要原因之一,本项前瞻性、随机化临床试验,旨在探讨围手术期使用普罗布考能否降低冠状动脉介入性诊断及治疗术后的急性肾损害.方法 连续筛选2007年11月1日至2008年4月31日在天津医科大学第二医院心脏科因不稳定性心绞痛入院,拟行冠状动脉造影和(或)冠状动脉介入治疗术的患者205例.随机分入普罗布考组(102例)及对照组(103例).普罗布考组患者于术前及术后3 d服用普罗布考500 mg,2次/d.介入术中使用低渗非离子型对比剂-碘海醇.术后全部患者立即接受水化治疗12 h(1 ml·kg-1·h-1).入院时及术后3 d连续监测肾功能.术后72 h内血清肌酐(Scr)较基线值增高25%或44.2 μol/L(0.5 mg/a)定义为CIAKI.结果 两组患者大部分基线指标差异无统计学意义.总CIAKI发生率为11.22%.多因素回归分析显示,基线Scr≥132.6 μmol/L(OR=21.11,95%CI 1.95～56.06,P＜0.001)、肌酐清除率(Ccr)＜60 ml/min(OR=4.19,95%CI 1.94～9.05,P＜0.001)、心功能＞Ⅱ级(NYHA)(OR=6.23,95%CI 2.73～14.21,P＜0.001)、糖尿病(OR=2.049,95%GI 1.19～5.25,P＜0.001)、年龄≥70岁(OR=3.52,95%CI 1.66～7.43,P＜0.001)、冠状动脉造影显示的冠状动脉钙化(OR=4.29,95%CI 1.99～9.24,P＜0.001)等因素与CIAKI相关.普罗布考组CIAKI发生率较对照组轻度下降(7.84%比14.56%),但差异无统计学意义.普罗布考组与对照组相比,术后Scr峰值[(101.62±42.98)μmol/L比(117.67±68.77)μmol/L,P=0.047]及其与基线Scr的差值(△Scr)[(13.49±19.61)μmol/L比(22.50±18.31)μmol/L,P=0.001]明显降低.结论 对不稳定性心绞痛接受冠状动脉造影和(或)冠状动脉介入治疗的患者在围手术期预防性使用普罗布考具有保护肾功能,减轻肾损害的作用.

Role of probucol in preventing contrast induced acute kidney injury after coronary interventional procedure: a randomized trial

Objective Contrast induced acute kidney injury (CIAKI) is a significant clinical problem. We, therefore, performed a prospective, randomized trial to investigate the role of probueol in the prevention of CIAKI in patients with unstable angina pectoris (UAP) undergoing percutaneous coronary angiography (CAG) and interventions (PCI). Methods We studied 205 patients with UAP, who underwent CAG or PCI prospectively. Patients were randomly assigned to probucol group (n = 102) and control group (n= 103). In the probucol group, the patients received probucol tablets 500 mg b. i. d for 3 days before and after intervcntion. All the patients, after intervention, underwent hydration with intravenous saline at a rate of 1 ml per kilogram of body weight per hour for 12 hours. Results Patients were well-matched with no significant differenced at baseline in majority measured parameters between two groups. CIAKI occurred in 23 of the 205 (11.22%) patients. Multivariate logistic regression was used to identify correlates of CIAKI and clinical data. CIAKI was most strongly associated with Scr≥132.6 μmol/L (OR =21.11,95% CI 1.95-56. 06, P＜0.001), Ccr ＜60 ml/min (OR =4.19, 95%(2/1.94-9.05, P ＜0.001), heart function ＞ class Ⅱ (OR = 6.23, 95% CI 2.73-14.21, P ＜ 0.001), Diabetes (OR = 2.049, 95% CI1.19-5.25, P ＜ 0.001), age ≥ 70 yrs (OR = 3.52, 95% CI 1.66-7.43, P ＜ 0.001), coronary artery calcification shown by CAG (OR =4.29, 95% CI 1.99-9.24, P ＜ 0.001). The rate of CIAKI in probueol groups was slightly lower compared with control group (7.84% vs. 14.56%), without significant difference. The post-procedure mean peak of Scr [(101.62±42. 98) μmol/L vs. (117.67 ～68.77) μmol/L, P =0.047] and the post-procedure increasing Ser from baseline (ASer) [(13.49 ± 19. 61) μmoL/L vs.(22.50 ± 18.31) μmol/L, P =0.001] in the probucol group decreased significantly compared with that of control group. Conclusion Prophylactic treatment with probueol 500 mg b. i. d during periproeedural stage in patients with UAP has preventing role against CIAK1 after cardiac catheterization.