钆喷酸葡胺和钆特酸对大鼠肾脏的影响：一项比较研究。

Effects of Gadodiamide and Gadoteric Acid on Rat Kidneys: A Comparative Study.

机构信息

Recep Tayyip Erdogan University Faculty of Medicine, Department of Radiology, Rize, Turkey.

Recep Tayyip Erdogan University Faculty of Medicine, Department of Histology and Embryology, Rize, Turkey.

出版信息

J Magn Reson Imaging. 2019 Feb;49(2):382-389. doi: 10.1002/jmri.26266. Epub 2018 Sep 13.

DOI:10.1002/jmri.26266

PMID:30209850

Abstract

BACKGROUND

Gadolinium-based contrast agents are complex chelates to provide contrast in NRI. However, recent studies have highlighted the deposition of free Gd ion in various tissues.

PURPOSE

To evaluate the histopathological and immunohistochemical changes on rat kidney tissue following both macrocyclic (gadoteric acid) and linear (gadodiamide) agents under the hypothesis that gadolinium-based contrast agents (GBCA) lead to toxic, free Gd accumulation in tissues.

STUDY TYPE

The local Animal Care Committee approved the prospective animal study.

ANIMAL MODEL

Thirty-two healthy Sprague-Dawley male rats were administered 2 mmol/kg gadodiamide and gadoteric acid for the first 4 days for 5 weeks. Group 1 received no drug (control, n = 8) and Group 2 (n = 8) was administered 0.1 ml/kg saline. Group 3 was administered 0.1 mmol/kg gadodiamide and Group 4 (n = 8) was administered 2 mmol/kg gadoteric acid.

ASSESSMENT

Biochemical, histopathological, and immunohistochemical changes in testis kidney tissue were evaluated at the end of 10 weeks.

STATISTICAL TESTS

Differences between groups were analyzed using the nonparametric Kruskal-Wallis test followed by one-way analysis of variance and the Tamhane test, also followed by Turkey's HSD test.

RESULTS

Gadolinium increased serum urea, Ca , and Caspase-3 positive tubular cell number. Larger Bowman capsules shrank proximal and distal tubules were revealed in the gadodiamide and gadoteric acid groups compared to the control group (P < 0.05). Histopathologic examination showed significantly more interstitial fibrosis, amyloid deposits, and vasocongestion in the gadodiamide group than the gadoteric acid and control groups, while the gadoteric acid group demonstrated significantly more leukocytic infiltration with atrophied proximal and distal tubules than the gadodiamide and control groups (P < 0.05).

DATA CONCLUSION

GBCA administration causes significant histopathologic changes in kidney tissue. This study advocates additional investigation to assess the in vivo safety of GBCAs.

LEVEL OF EVIDENCE

1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:382-389.

摘要

背景

钆基对比剂是提供 NRI 对比的复杂螯合物。然而，最近的研究强调了游离 Gd 离子在各种组织中的沉积。

目的

评估大环（钆特酸）和线性（钆喷酸葡胺）制剂对大鼠肾脏组织的组织病理学和免疫组织化学变化，假设钆基对比剂（GBCA）导致组织中有毒的游离 Gd 积累。

研究类型

当地动物护理委员会批准了这项前瞻性动物研究。

动物模型

32 只健康的 Sprague-Dawley 雄性大鼠在前 4 天内给予 2mmol/kg 钆喷酸葡胺和钆特酸，每周 5 次。第 1 组未给予药物（对照组，n=8），第 2 组（n=8）给予 0.1ml/kg 生理盐水。第 3 组给予 0.1mmol/kg 钆喷酸葡胺，第 4 组（n=8）给予 2mmol/kg 钆特酸。

评估

在第 10 周末评估睾丸肾脏组织的生化、组织病理学和免疫组织化学变化。

统计学检验

使用非参数 Kruskal-Wallis 检验分析组间差异，然后进行单因素方差分析和 Tamhane 检验，也进行 Turkey 的 HSD 检验。

结果

钆增加了血清尿素、钙和 Caspase-3 阳性肾小管细胞的数量。与对照组相比，钆喷酸葡胺和钆特酸组的肾小球囊明显缩小，近端和远端肾小管萎缩（P<0.05）。组织病理学检查显示，与钆特酸和对照组相比，钆喷酸葡胺组的间质纤维化、淀粉样沉积和血管充血明显更多，而与钆喷酸葡胺和对照组相比，钆特酸组的白细胞浸润和近端及远端肾小管萎缩明显更多（P<0.05）。