Transcutaneous assessment of renal function in conscious rats with a device for measuring FITC-sinistrin disappearance curves

Transcutaneous assessment of renal function in conscious rats with a device for measuring FITC-sinistrin disappearance curves
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DOI:
10.1038/ki.2011.31
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发表时间:
2011-06-01
影响因子:
19.6
通讯作者:
Gretz, Norbert
Gretz, Norbert
中科院分区:
医学1区
文献类型:
--
作者:
Schock-Kusch, Daniel;Xie, Qing;Gretz, Norbert

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尿液或血浆清除量的测定被认为是测量肾小球滤过率(GFR)的金标准。在这里,我们描述了一种技术,可以根据经皮测量的异硫氰酸荧光素(FITC)-左旋司汀的消除动力学来确定肾功能,FITC标记的活性药物成分是GFR的商业标记物。一种低成本的设备可在480 nm处经皮激发FITC-左旋斯特林,并在520 nm处检测透过皮肤的发射光。射频传输允许远程监测和实时分析FITC-左旋司汀的排泄,作为肾功能的标志。由于小型化,整个设备可以安装在自由活动的大鼠的背部,不需要采集血液样本或进行实验室分析。作为原理的证明,比较了自由活动的健康大鼠、单侧肾切除所致的肾功能减退的大鼠和伴有囊性肾病的PKD/MHM大鼠的FITC-左旋司特林的经皮和血浆消除动力学。结果显示,在所有动物组中,消除半衰期和GFR值具有高度可比性。Bland-Altman酶学分析与经皮测得的GFR相比,每100克体重的平均偏差(偏差)为0.01,a-0.30~0.33ml/min,95%的限值符合。因此,使用这种装置,可以可靠地测量自由活动的大鼠的肾功能,而不需要麻醉和对肾功能的影响。《国际肾脏》(2011年)79,12541258;doi:10.1038/ki.2011.31;2011年3月2日在线发布
Determination of the urinary or plasma clearance of exogenous renal markers, such as inulin or iohexol, is considered to be the gold standard for glomerular filtration rate (GFR) measurement. Here, we describe a technique allowing determination of renal function based on transcutaneously measured elimination kinetics of fluorescein isothiocyanate (FITC)-sinistrin, the FITC-labeled active pharmaceutical ingredient of a commercially available marker of GFR. A low cost device transcutaneously excites FITC-sinistrin at 480 nm and detects the emitted light through the skin at 520nm. A radio-frequency transmission allows remote monitoring and real-time analysis of FITC-sinistrin excretion as a marker of renal function. Due to miniaturization, the whole device fits on the back of freely moving rats, and requires neither blood sampling nor laboratory assays. As proof of principle, comparative measurements of transcutaneous and plasma elimination kinetics of FITC-sinistrin were compared in freely moving healthy rats, rats showing reduced kidney function due to unilateral nephrectomy and PKD/Mhm rats with cystic kidney disease. Results show highly comparable elimination half-lives and GFR values in all animal groups. Bland-Altman analysis of enzymatically compared with transcutaneously measured GFR found a mean difference (bias) of 0.01 and a -0.30 to 0.33 ml/min per 100 g body weight with 95% limit of agreement. Thus, with this device, renal function can be reliably measured in freely moving rats eliminating the need for and influence of anesthesia on renal function. Kidney International (2011) 79, 1254-1258; doi:10.1038/ki.2011.31; published online 2 March 2011