Efficacy of preventive interventions for iodinated contrast-induced acute kidney injury evaluated by intrarenal oxygenation as an early marker.
Efficacy of preventive interventions for iodinated contrast-induced acute kidney injury evaluated by intrarenal oxygenation as an early marker.
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DOI：
10.1097/rli.0000000000000065
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发表时间：
2014-10
影响因子：
6.7
通讯作者：
Prasad PV
中科院分区：
文献类型：
--
作者：
Li LP;Thacker J;Lu J;Franklin T;Zhou Y;Papadopoulou MV;Solomon R;Prasad PV
本研究的目的是通过血氧水平依赖（BOLD）磁共振成像（MRI）结合尿中性粒细胞明胶酶相关脂钙蛋白（NGAL）测量，评估潜在的肾保护干预措施(如n -乙酰半胱氨酸（NAC；抗氧化剂）和速尿酰胺（利尿剂）对肾内氧合的影响。大鼠在接受NAC、速尿或安慰剂干预之前，分别给予一氧化氮合酶抑制剂L-NAME （10 mg/kg）和环氧合酶抑制剂吲哚美辛（10 mg/kg），以诱导发生碘造造剂诱导的急性肾损伤的风险。然后给予三种碘化造影剂（碘己醇、碘草酸酯或碘二沙醇）中的一种（每公斤体重1600毫克有机碘）。54只Sprague-Dawley大鼠根据所接受的干预和造影剂的不同，随机分为9组。在L-NAME、吲哚美辛、干预或安慰剂和碘化造影剂后，在西门子3.0-T扫描仪上使用多重梯度回忆回声序列获得血氧水平依赖的mri加权图像。数据采集和分析采用盲法进行。R2* (=1/T2*)地图在扫描仪上内嵌生成。采用一阶自回归方差-协方差混合效应生长曲线模型对时间数据进行分析。尿NGAL是急性肾损伤的标志物，在注射造影剂后的基线、2和4小时进行测量。与安慰剂组比较，速尿组肾外髓质内条R2*升高率明显低于安慰剂组（P < 0.05）。与对照组相比，NAC组大鼠R2*的增加率较低，但差异无统计学意义。尿NGAL R2*在给予碘沙醇后，呋塞米预处理大鼠的R2*几乎没有增加，而NAC或安慰剂预处理大鼠的R2*有显著增加（P < 0.05）。这是第一个使用BOLD MRI评估干预措施减轻造影剂有害影响的研究。通过NGAL评估，给予碘化造影剂后R2*的增加速率与急性肾损伤相关。需要进一步的研究来确定呋塞米和NAC的最佳剂量，以减轻造影剂的不良影响。由于NGAL已被证明可用于记录碘造影剂诱导的急性肾损伤，因此本研究中使用BOLD MRI和NGAL测量的方法可应用于人类。
The objective of this study was to evaluate the effects of potential renoprotective interventions such as the administration of N-acetylcysteine (NAC; antioxidant) and furosemide (diuretic) on intrarenal oxygenation as evaluated by blood oxygen level–dependent (BOLD) magnetic resonance imaging (MRI) in combination with urinary neutrophil gelatinase–associated lipocalin (NGAL) measurements. Rats received nitric oxide synthase inhibitor L-NAME (10 mg/kg) and cyclooxygenase inhibitor indomethacin (10 mg/kg) to induce the risk for developing iodinated contrast-induced acute kidney injury before receiving one of the interventions: NAC, furosemide, or placebo. One of the 3 iodinated contrast agents (iohexol, ioxaglate, or iodixanol) was then administered (1600-mg organic iodine per kilogram body weight). Fifty-four Sprague-Dawley rats were allocated in a random order into 9 groups on the basis of the intervention and the contrast agent received. Blood-oxygen-level–dependent MRI–weighted images were acquired on a Siemens 3.0-T scanner using a multiple gradient recalled echo sequence at baseline, after L-NAME, indomethacin, interventions or placebo, and iodinated contrast agents. Data acquisition and analysis were performed in a blind fashion. R2* (=1/T2*) maps were generated inline on the scanner. A mixed-effects growth curve model with first-order autoregressive variance-covariance was used to analyze the temporal data. Urinary NGAL, a marker of acute kidney injury, was measured at baseline, 2 and 4 hours after the contrast injection. Compared with the placebo-treated rats, those treated with furosemide showed a significantly lower rate of increase in R2* (P < 0.05) in the renal inner stripe of the outer medulla. The rats treated with NAC showed a lower rate of increase in R2* compared with the controls, but the difference did not reach statistical significance. Urinary NGAL showed little to no increase in R2* after administration of iodixanol in the rats pretreated with furosemide but demonstrated significant increase in the rats pretreated with NAC or placebo (P < 0.05). This is the first study to evaluate the effects of interventions to mitigate the deleterious effects of contrast media using BOLD MRI. The rate of increase in R2* after administration of iodinated contrast is associated with acute renal injury as evaluated by NGAL. Further studies are warranted to determine the optimum dose of furosemide and NAC for mitigating the ill effects of contrast media. Because NGAL has been shown to be useful in humans to document iodinated contrast-induced acute kidney injury, the method presented in this study using BOLD MRI and NGAL measurements can be translated to humans.