氨氯地平和培哚普利预防放射造影剂肾毒性前瞻性随机临床研究(英文)

Prevention of radiocontrast-media-induced nephrotoxicity by perindopril and amlodipine in humans

目的 研究培哚普利和氨氯地平对放射造影剂肾毒性的保护作用 ,并探讨一氧化氮 (NO)在造影剂肾毒性发病机制中的作用。方法 2 97例静脉肾盂造影患者被随机分为 3组 ,即氨氯地平组、培哚普利组和对照组。注射 76 %泛影葡胺前 1h ,双盲法随机分别给予氨氯地平 (5mg)、培哚普利 (4mg)或安慰剂 ,造影前 2 4h和造影后 4 8h测内生肌酐清除率 (CrCl) ,并检测造影前后 2 4h尿中NO、白蛋白、N -乙酰基 - β -氨基葡萄糖苷酶 (NAG)及视黄醇结合蛋白 (RBP)含量。造影后 4 8h血清肌酐较基础值增高 2 5 %或 0 .5ml/dl定义为造影剂肾毒性。结果 安慰剂组尿中白蛋白、RBP、NAG显著升高 (P <0 .0 5 ) ,NO显著降低 (P <0 .0 5 ) ;造影后 4 8hCcr下降 (P <0 .0 5 )。培哚普利组Ccr、尿中NO、白蛋白、NAG和RBP的含量均无明显变化 (P >0 .0 5 )。氨氯地平组Ccr ,尿NO和RBP的含量亦无明显变化 (P >0 .0 5 )。但尿NAG含量增高 (P <0 .0 5 )。氨氯地平和培哚普利组尿RBP水平和造影剂肾毒性发生率均较对照组低 (P <0 .0 5 )。结论 造影前口服单剂量氨氯地平或者培哚普利均能有效预防造影剂肾毒性 ,NO可能在造影剂肾毒性发病机制中起重要作用。

Objective:To investigate the protective role of perindopril and amlodipine in radiocontrast-media-induced nephrotoxicity in humans. Urinary nitric oxide (NO) was also measured to assess its potential pathophysiologic role.Methods:Two hundreds and ninety-seven patients being scheduled for intravenous pyelography were enrolled in this study. One hour before injection of the contrast agent meglumine diatrizoate, patients randomly received amlodipine, perindopril, or placebo in a blind manner. We measured the creatinine clearance (CrCl) on the day before and 2 days after exposure to contrast media. Urinary excretion of NO, albumin, N-acetyl-β-glucosaminidase (NAG) and retinol-binding protein (RBP) was also determined 1 day before and after contrast exposure. A 25% or 0.5?mg/ml increase in serum creatinine 48 hours after radiocontrast administration was defined as contrast nephrotoxicity.Results:In the placebo group, exposure to contrast significantly increased urinary excretion of albumin, RBP and NAG (P<0.05). Urinary excretion of NO decreased significantly (P< 0.05). 48 hours after contrast administration, CrCl decreased (P<0.05). In patients receiving perindopril, exposure to contrast did not change urinary excretion of NO, RBP, NAG and CrCl (P>0.05). In the amlodipine group, contrast exposure did not change CrCl and urinary excretion of NO and RBP (P> 0.05), but urinary excretion of NAG increased (P< 0.05). In patients receiving perindopril or amlodipine, urine RBP was lower than that in the control group (P<0.05), contrast media-associated nephropathy was significantly reduced (P<0.05).Conclusions:A single dose of amlodipine or perindopril per os before radio-contrast administration can effectively prevent radiocontrast-media-induced nephrotoxicity. NO may play a role in the pathogenesis of radio-contrast induced nephrotoxicity.