Evaluation of intrarenal oxygenation in iodinated contrast-induced acute kidney injury-susceptible rats by blood oxygen level-dependent magnetic resonance imaging.
Evaluation of intrarenal oxygenation in iodinated contrast-induced acute kidney injury-susceptible rats by blood oxygen level-dependent magnetic resonance imaging.
复制标题
通过血氧水平依赖性磁共振成像评估碘对比度诱导的急性肾损伤敏感大鼠的肾内充氧。
DOI：
10.1097/rli.0000000000000031
复制
发表时间：
2014-06
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;Lu J;Zhou Y;Papadopoulou MV;Franklin T;Bokhary U;Solomon R;Sen A;Prasad PV
本研究的目的是评价对比剂诱导的急性肾损伤（CIAKI）敏感大鼠在使用4种具有不同理化性质的造影剂时，通过血氧水平依赖性（BOLD）磁共振成像评估的肾内氧合差异，并证明在该模型中采集尿中性粒细胞明胶酶相关脂质运载蛋白（NGAL）水平作为CIAKI标志物的可行性。我们的机构动物护理和使用委员会批准了这项研究。将66只SD大鼠分为CIAKI易感组（给予一氧化氮合酶抑制剂N-硝基-L-精氨酸甲酯[10 mg/kg]和环氧化酶抑制剂吲哚美辛[10 mg/kg]）和对照组（给予生理盐水）。然后给予4种碘化造影剂（碘酞酸盐、碘海醇、碘克沙酸盐或碘克沙醇）之一（1600 mg有机碘/kg体重）。在使用N-硝基-L-精氨酸甲酯（或生理盐水）、吲哚美辛（或生理盐水）和碘化造影剂（或安慰剂）后，在Siemens 3.0-T扫描仪上使用多梯度回波序列采集多个血氧水平依赖性磁共振图像。在扫描仪上内联生成R2*（R2* = 1/T2*）图。采用一阶自回归方差-协方差的混合效应生长曲线模型对时间数据进行分析。在2个亚组中，在注射造影剂后4小时测量尿NGAL，这是肾损伤的标志物（与血清肌酐不同）。在所有4个肾脏区域中观察到造影剂之间血氧水平依赖性磁共振成像结果的差异。然而，CIAKI敏感组的外髓内纹（ISOM）显示出最明显的变化，并且所有4种造影剂的R2* 随时间推移显著增加（P < 0.01）。在对照组中，仅碘克沙醇显示R2* 随时间增加（P < 0.05）。ISOM中NGAL和R2* 值的增加之间存在一致性。在对CIAKI易感的大鼠中，与接受安慰剂的大鼠相比，接受造影剂的大鼠肾脏ISOM的R2* 显著增加。ISOM中NGAL和R2* 值之间的一致性表明，注射造影剂后观察到的R2* 立即增加可能是肾损伤的最早生物标志物。需要进一步研究以确定与急性肾损伤相关的R2* 阈值，并说明R2* 对肾氧合状态的特异性。
The objectives of this study were to evaluate differences in intrarenal oxygenation as assessed by blood oxygen level–dependent (BOLD) magnetic resonance imaging in contrast-induced acute kidney injury (CIAKI)–susceptible rats when using 4 contrast media with different physicochemical properties and to demonstrate the feasibility of acquiring urinary neutrophil gelatinase–associated lipocalin (NGAL) levels as a marker of CIAKI in this model. Our institutional animal care and use committee approved the study. Sixty-six Sprague-Dawley rats were divided into CIAKI-susceptible groups (received nitric oxide synthase inhibitor N-nitro-L-arginine methyl ester [10 mg/kg] and cycloxygenase inhibitor indomethacin [10mg/kg]) and control groups (received saline instead). One of the 4 iodinated contrast agents (iothalamate, iohexol, ioxaglate, or iodixanol) was then administered (1600-mg organic iodine per kilogram of body weight). Multiple blood oxygen level–dependent magnetic resonance images were acquired on a Siemens 3.0-T scanner using a multiple gradient recalled echo sequence at baseline, after N-nitro-L-arginine methyl ester (or saline), indomethacin (or saline), and iodinated contrast agent (or placebo). R2* (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 kidney injury (unlike serum creatinine), was measured 4 hours after contrast injection in the 2 subgroups. Differences in blood oxygen level–dependent magnetic resonance imaging results between the contrast media were observed in all 4 renal regions. However, the inner stripe of the outer medulla (ISOM) showed the most pronounced changes in the CIAKI-susceptible group and R2* increased significantly (P < 0.01) over time with all 4 contrast media. In the control groups, only iodixanol showed an increase in R2* (P < 0.05) over time. There was an agreement between increases in NGAL and R2* values in ISOM. In rats susceptible to CIAKI, those receiving contrast media had significant increases in R2* in renal ISOM compared with those receiving placebo. The agreement between NGAL and R2* values in the ISOM suggests that the observed immediate increase in R2* after contrast injection may be the earliest biomarker of renal injury. Further studies are necessary to establish threshold values of R2* associated with acute kidney injury and address the specificity of R2* to renal oxygenation status.