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首页> 外文期刊>Investigative radiology >Impact of renal impairment on long-term retention of gadolinium in the rodent skin following the administration of gadolinium-based contrast agents.
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Impact of renal impairment on long-term retention of gadolinium in the rodent skin following the administration of gadolinium-based contrast agents.

机译：施用impairment类造影剂后，肾功能损害对of在啮齿动物皮肤中长期保留的影响。

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OBJECTIVE: Several publications have suggested a possible association between Gd-based contrast agents (GBCAs) and the development of nephrogenic systemic fibrosis, a rare but serious disease. To date, nephrogenic systemic fibrosis has been observed only in patients with severe renal insufficiency.The aim of this study was to determine the impact of a prolonged circulation time of GBCAs caused by reduced renal clearance on the long-term retention of Gd in the skin of rats after administration of different GBCAs. MATERIAL AND METHODS: Renally impaired Han Wistar Rats (5/6-nephrectomized rats) were injected with Omniscan, OptiMARK, Magnevist, or Gadovist. The contrast agents were administered once daily for 5 consecutive days into the tail vein at a dose of 2.5 mmol Gd/kg b.w. Skin biopsies were taken at various time points, and the gadolinium (Gd) concentration was determined by inductive coupled plasma mass spectrometry (ICP-MS) over an observation period of 168 days post injection (p.i.). RESULTS: Differences in the skin Gd concentrations were observed between the 4 investigated GBCAs. For the nonionic linear compounds, Omniscan and OptiMARK, high Gd concentrations were maintained in the skin over the observation period of up to 168 days p.i. For the ionic linear compound, Magnevist, comparatively lower Gd retention in the skin was observed over time. For the macrocyclic compound, Gadovist, the Gd values in the skin were even lower, and significantly lower than Gd values in the skin in Omniscan and OptiMARK treated animals. CONCLUSION: The results of this preclinical study support the use of 5/6-nephrectomized rats as a model for prolonged circulation time of GBCAs as seen in patients with severe renal impairment. Surgically induced severe renal impairment resulted in delayed clearance of the administered GBCAs in the study animals. The highest amount of Gd was observed in the skin after treatment with the nonionic linear GBCAs, whereas the lowest Gd values were observed after treatment with the macrocyclic agent. This suggests that the difference in the Gd values observed in rat skin tissue after treatment with the different GBCAs is caused of a different propensity of the different GBCAs to release Gd in vivo. However, the analytical method used does not distinguish between chelated and unchelated Gd.
机译：目的：几篇出版物提出基于Gd的造影剂（GBCA）与肾源性系统性纤维化（一种罕见但严重的疾病）的发展之间可能存在关联。迄今为止，仅在严重肾功能不全的患者中观察到了肾原性系统性纤维化。本研究的目的是确定肾清除率降低导致GBCAs循环时间延长对Gd在皮肤中长期保留的影响服用不同GBCA后的大鼠数量。材料与方法：给肾功能受损的汉Wistar大鼠（5/6肾切除的大鼠）注射Omniscan，OptiMARK，Magnevist或Gadovist。每天两次连续5天将造影剂以2.5 mmol Gd / kg b.w的剂量注入尾静脉。在不同时间点进行皮肤活检，并在注射后168天的观察期内通过电感耦合等离子体质谱（ICP-MS）测定g（Gd）的浓度（p.i.）。结果：在四个研究的GBCA之间观察到皮肤Gd浓度的差异。对于非离子线性化合物Omniscan和OptiMARK，在长达168天p.i的观察期内，皮肤中均保持了高Gd浓度。对于离子线性化合物Magnevist，随着时间的推移，观察到Gd在皮肤中的保留率相对较低。对于大环化合物Gadovist，皮肤中的Gd值甚至更低，并且显着低于Omniscan和OptiMARK处理过的动物的皮肤中Gd值。结论：这项临床前研究的结果支持使用5/6肾切除的大鼠作为GBCAs延长循环时间的模型，如重度肾功能不全患者所见。手术引起的严重肾功能损害导致研究动物中GBCA的清除延迟。用非离子型线性GBCAs处理后，皮肤中的Gd含量最高，而用大环剂处理后，Gd值最低。这表明在用不同的GBCAs治疗后在大鼠皮肤组织中观察到的Gd值的差异是由于不同的GBCAs在体内释放Gd的倾向不同引起的。但是，所使用的分析方法不能区分螯合的Gd和未螯合的Gd。

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