Abstract

Purpose

The kidney is a radiosensitive late-responding normal tissue. Injury is characterized by radiation nephropathy and decline of glomerular filtration rate (GFR). The current study aimed to compare two rapid and cost-effective methodologies of assessing GFR against more conventional biomarker measurements.

Methods

C57BL/6 mice were treated with bilateral focal X-irradiation (1x14Gy or 5x6Gy). Functional measurements of kidney injury were assessed 20 weeks post-treatment. GFR was estimated using a transcutaneous measurement of fluorescein-isothiocyanate conjugated (FITC)-sinistrin renal excretion and also dynamic contrast-enhanced CT imaging with a contrast agent (ISOVUE-300 Iopamidol).

Results

Hematoxylin and eosin (H&E) and Periodic acid-Schiff staining identified comparable radiation-induced glomerular atrophy and mesangial matrix accumulation after both radiation schedules, respectively, although the fractionated regimen resulted in less diffuse tubulointerstitial fibrosis. Albumin-to-creatinine ratios (ACR) increased after irradiation (1x14Gy: 100.4 ± 12.2 µg/mg; 6x5Gy: 80.4 ± 3.02 µg/mg) and were double that of nontreated controls (44.9 ± 3.64 µg/mg). GFR defined by both techniques was negatively correlated with BUN, mesangial expansion score, and serum creatinine. The FITC-sinistrin transcutaneous method was more rapid and can be used to assess GFR in conscious animals, dynamic contrast-enhanced CT imaging technique was equally safe and effective.

Conclusion

This study demonstrated that GFR measured by dynamic contrast-enhanced CT imaging is safe and effective compared to transcutaneous methodology to estimate kidney function.

中文翻译：

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小鼠辐射肾损伤的无创评估

 抽象的

 目的

肾脏是放射敏感的迟反应正常组织。损伤的特征是放射性肾病和肾小球滤过率（GFR）下降。当前的研究旨在比较两种快速且经济高效的 GFR 评估方法与更传统的生物标志物测量方法。

 方法

C57BL/6 小鼠接受双侧焦点 X 射线照射（1x14Gy 或 5x6Gy）。治疗后20周评估肾损伤的功能测量。通过经皮测量荧光素-异硫氰酸酯结合物 (FITC)-西尼斯特林肾排泄以及使用造影剂 (ISOVUE-300 碘帕醇) 的动态增强 CT 成像来估计 GFR。

 结果

苏木精和伊红 (H&E) 和高碘酸-希夫染色分别在两种放射方案后发现了类似的放射诱导的肾小球萎缩和系膜基质积累，尽管分次治疗导致弥漫性肾小管间质纤维化较少。照射后白蛋白与肌酐比率 (ACR) 增加（1x14Gy：100.4 ± 12.2 µg/mg；6x5Gy：80.4 ± 3.02 µg/mg），是未治疗对照组的两倍（44.9 ± 3.64 µg/mg）。两种技术定义的 GFR 与 BUN、系膜扩张评分和血清肌酐呈负相关。 FITC-sinistrin经皮方法更快速，可用于评估清醒动物的GFR，动态增强CT成像技术同样安全有效。

 结论

这项研究表明，与经皮方法相比，通过动态对比增强 CT 成像测量 GFR 来评估肾功能是安全有效的。