From the Departments of *Radiology and Radiological Sciences; †Neurosurgery and Hematology/Oncology, and ‡Pathology, Medical University of South Carolina, Charleston, SC; §Departments of Radiology and Neurological Surgery, University of Washington, Seattle, WA; ∥Department of Physical Medicine & Rehabilitation and ¶Dermatology & Dermatologic Surgery, Medical University of South Carolina; and #National Institute of Standards and Technology, Chemical Sciences Division, Charleston, SC.
Invest Radiol. 2016 May;51(5):280-9. doi: 10.1097/RLI.0000000000000266.
The aim of this study was to assess gadolinium deposition in the skin of a patient with normal renal function, based on estimated glomerular filtration rate values greater than 59 mL/min/1.73 m(2) after exposure to large cumulative doses of gadolinium-based contrast agents (GBCAs).
The patient underwent 61 contrasted brain MRI scans over the course of 11 years. Skin biopsies from the forearm and lower extremity were analyzed with inductively coupled plasma mass spectrometry (ICP-MS), laser ablation ICP-MS, and hydrophilic interaction liquid chromatography ICP-MS.
The ICP-MS demonstrated high levels of gadolinium deposition (14.5 ± 0.4 μg/g), similar to previously reported gadolinium levels within the skin of patients with nephrogenic systemic fibrosis. The laser ablation ICP-MS demonstrated deposition of gadolinium within the deep layers of skin. Speciation analysis using hydrophilic interaction liquid chromatography ICP-MS demonstrated the presence of intact gadolinium-chelate species, although most of the gadolinium present could not be further characterized. Light microscopy demonstrated increased CD34 immunoreactivity in the connective tissue septations of the subcutaneous adipose tissue. The patient had no history of skin disorders and did not have a history of nephrogenic systemic fibrosis but did have severe joint contractures of unknown etiology.
Our results, in contradiction to published literature, suggest that in patients with normal renal function, exposure to GBCAs in extremely high cumulative doses can lead to significant gadolinium deposition in the skin. This finding is in line with more recent reports of gadolinium deposition in the brain of patients with normal renal function. Future studies are required to address possible clinical consequences of gadolinium deposition in the skin, brain, and potentially other organs in patients with normal renal function. We recommend, in addition to following current US Food and Drug Administration and American College of Radiology guidelines based on estimated glomerular filtration rate values, that caution be used when administering large cumulative doses of GBCAs and that total cumulative dose of each agent administered is recorded in the patient's medical record.
本研究旨在评估一名肾功能正常患者的皮肤中钆沉积情况,该患者在接受大剂量累积钆对比剂(GBCA)后估算肾小球滤过率(eGFR)值大于 59 mL/min/1.73 m2。
患者在 11 年期间共进行了 61 次对比增强脑 MRI 扫描。对前臂和下肢的皮肤活检标本进行电感耦合等离子体质谱(ICP-MS)、激光烧蚀 ICP-MS 和亲水相互作用液相色谱 ICP-MS 分析。
ICP-MS 显示皮肤中存在高水平的钆沉积(14.5 ± 0.4 μg/g),与先前报道的伴有肾源性系统性纤维化患者皮肤中的钆水平相似。激光烧蚀 ICP-MS 显示钆沉积在皮肤的深层。亲水相互作用液相色谱 ICP-MS 形态分析显示存在完整的钆螯合物,但大部分的钆无法进一步表征。光镜显示皮下脂肪组织结缔组织间隔的 CD34 免疫反应性增强。患者无皮肤疾病史,也无肾源性系统性纤维化病史,但有原因不明的严重关节挛缩。
与已发表文献相反,我们的结果表明,在肾功能正常的患者中,暴露于极高累积剂量的 GBCA 可导致皮肤中出现显著的钆沉积。这一发现与最近报道的肾功能正常患者脑内钆沉积相一致。需要进一步的研究来阐明肾功能正常患者皮肤、脑内以及潜在其他器官内钆沉积的可能临床后果。我们建议,除了遵循目前基于 eGFR 值的美国食品药品监督管理局和美国放射学院的指南外,在给予大剂量累积 GBCA 时应谨慎,并在患者的病历中记录每次给予的每种药物的总累积剂量。