Circulation:阿托伐他汀预治疗可降造影剂诱发急性肾损伤发生率

2013-01-22 Circulation CMT 高晓方 编译

  意大利学者的一项研究表明,造影剂应用前24小时内单次给予大剂量阿托伐他汀可有效降低造影剂诱发急性肾损伤(CIAKI)发生率。论文发表于《循环》[Circulation 2012, 126(25):3008]。   此项研究包括体内和体外试验两部分。在体内研究中,慢性肾病患者被随机分为阿托伐他汀组(造影剂暴露前24小时内给予80 mg阿托伐他汀;202例)和对照组

  意大利学者的一项研究表明,造影剂应用前24小时内单次给予大剂量阿托伐他汀可有效降低造影剂诱发急性肾损伤(CIAKI)发生率。论文发表于《循环》[Circulation 2012, 126(25):3008]。

  此项研究包括体内和体外试验两部分。在体内研究中,慢性肾病患者被随机分为阿托伐他汀组(造影剂暴露前24小时内给予80 mg阿托伐他汀;202例)和对照组(208例)。所有患者均接受大剂量N-乙酰半胱氨酸和碳酸氢钠溶液治疗。以造影剂暴露后24小时内胱蛋白酶抑制剂C浓度升高10%以上定义CIAKI。体外研究评估了阿托伐他汀预治疗对造影剂介导修饰胞内通路的影响;该通路可决定肾小管细胞凋亡或存活。

  结果显示,阿托伐他汀组和对照组的CIAKI发生率分别为4.5%(9/202)和17.8%(37/208;P=0.005)。在阿托伐他汀组中,伴和未伴糖尿病的中度慢性肾病患者均出现CIAKI发生率降低。体外研究显示,阿托伐他汀预治疗可通过减少激酶活化预防造影剂诱导的肾细胞凋亡,并可恢复由Akt和ERK通路介导的细胞存活信号。


Impact of a High Loading Dose of Atorvastatin on Contrast-Induced Acute Kidney Injury

Background
The role of statins in the prevention of contrast-induced acute kidney injury (CIAKI) is controversial.
Methods and Results
First, we investigated the in vivo effects of atorvastatin on CIAKI. Patients with chronic kidney disease enrolled in the Novel Approaches for Preventing or Limiting Events (NAPLES) II trial were randomly assigned to (1) the atorvastatin group (80 mg within 24 hours before contrast media [CM] exposure; n=202) or (2) the control group (n=208). All patients received a high dose of N-acetylcysteine and sodium bicarbonate solution. Second, we investigated the in vitro effects of atorvastatin pretreatment on CM-mediated modifications of intracellular pathways leading to apoptosis or survival in renal tubular cells. CIAKI (ie, an increase >10% of serum cystatin C concentration within 24 hours after CM exposure) occurred in 9 of 202 patients in the atorvastatin group (4.5%) and in 37 of 208 patients in the control group (17.8%) (P=0.005; odds ratio=0.22; 95% confidence interval, 0.07–0.69). CIAKI rate was lower in the atorvastatin group in both diabetics and nondiabetics and in patients with moderate chronic kidney disease (estimated glomerular filtration rate, 31–60 mL/min per 1.73 m2). In the in vitro model, pretreatment with atorvastatin (1) prevented CM-induced renal cell apoptosis by reducing stress kinases activation and (2) restored the survival signals (mediated by Akt and ERK pathways).
Conclusions
A single high loading dose of atorvastatin administered within 24 hours before CM exposure is effective in reducing the rate of CIAKI. This beneficial effect is observed only in patients at low to medium risk.

    

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    2013-01-24 sodoo

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