此項研究包括體內(nèi)和體外試驗兩部分。在體內(nèi)研究中，慢性腎病患者被隨機(jī)分為阿托伐他汀組（造影劑暴露前24小時內(nèi)給予80 mg阿托伐他??；202例）和對照組（208例）。所有患者均接受大劑量N-乙酰半胱氨酸和碳酸氫鈉溶液治療。以造影劑暴露后24小時內(nèi)胱蛋白酶抑制劑C濃度升高10%以上定義CIAKI。體外研究評估了阿托伐他汀預(yù)治療對造影劑介導(dǎo)修飾胞內(nèi)通路的影響；該通路可決定腎小管細(xì)胞凋亡或存活。

結(jié)果顯示，阿托伐他汀組和對照組的CIAKI發(fā)生率分別為4.5%（9/202）和17.8%（37/208；P=0.005）。在阿托伐他汀組中，伴和未伴糖尿病的中度慢性腎病患者均出現(xiàn)CIAKI發(fā)生率降低。體外研究顯示，阿托伐他汀預(yù)治療可通過減少激酶活化預(yù)防造影劑誘導(dǎo)的腎細(xì)胞凋亡，并可恢復(fù)由Akt和ERK通路介導(dǎo)的細(xì)胞存活信號。

The role of statins in the prevention of contrast-induced acute kidney injury (CIAKI) is controversial.

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).

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.