氨氯地平和培哚普利预防放射造影剂肾毒性前瞻随机临床研究

Effect of Perindopril or amlodipine on prevention of radiocontrast-media-induced nephrotoxicity

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 ,双盲法随机分别单次获得氨氯地平 (5mg)、培哚普利 (4mg)或安慰剂 ,造影前 2 4h和造影后 4 8h抽血检测血清肌酐 (SCr) ,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)水平。造影后 4 8hSCr较基础值增高 2 5 %或 4 4 2 μmol/L定义为造影剂肾毒性。 结果 :安慰剂组患者尿中白蛋白、RBP、NAG水平显著升高 (P <0 0 5 ) ,NO水平显著降低 (P <0 0 5 ) ;造影后 4 8hSCr水平增高 (P<0 0 5 )。培哚普利组SCr、尿中NO、白蛋白、NAG和RBP的水平均无明显变化 (P >0 0 5 )。氨氯地平组SCr、尿NO和RBP的水平亦无明显变化 (P >0 0 5 )。但尿NAG水平增高 (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 :患者造影前口服单剂量氨氯地平或者培哚普利对造影剂肾毒性有一定预防作用 ,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. Methodology:Two hundred ninety seven patients for intravenous pyelography were randomly divided into three groups, namely amlodipine group, perindopril group, and placebo group, and each received amlodipine, perindopril, or placebo in a blind manner one hour before injection of the contrast agent meglumine diatrizoate respectively. We analyzed the changes of serum creatinine 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) were also determined 1 day before and 1 day after contrast exposure. 25% or 44 2 μmol/L increase of 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), while urinary excretion of NO decreased significantly ( P <0 05). 48 hours after contrast administration, the levels of serum creatinine increased ( P <0 05). In patients receiving perindopril, exposure to contrast did not change urinary excretion of NO, RBP or NAG and the levels of serum creatinine remained constant ( P >0 05). In the amlodipine group, contrast exposure did not change of serum creatinine and urinary excretion of NO, or RBP ( P >0 05), but urinary excretion of NAG increased ( P <0 05). Conclusion:A single dose of amlodipine or perindopril is an effective prophylaxis before radio contrast administration. NO may play an important role in the pathogenesis of radio contrast induced nephrotoxicity.