Department of Pathology, SUNY Upstate Medical University, Syracuse, NY, USA.
Nephrol Dial Transplant. 2011 Nov;26(11):3616-26. doi: 10.1093/ndt/gfr085. Epub 2011 Mar 25.
Nephrogenic systemic fibrosis (NSF) is a systemic disorder of patients with severe renal insufficiency who have received gadolinium (Gd)-based magnetic resonance contrast agents (GBCAs). The causative association with Gd exposure was strengthened by the demonstration of Gd in various tissues of NSF patients, predominantly at the bulk chemical level. The distribution of Gd at the histologic level of organs other than skin has not been reported previously.
We analysed tissues from an autopsy case with verified advanced NSF by light microscopy and scanning electron microscopy/energy-dispersive X-ray spectroscopy. Furthermore, we reviewed published literature to compare the histological and histochemical findings in NSF patients and chronic renal failure (CRF) patients without NSF.
Insoluble Gd-phosphate deposits were detected in the skin, liver, lungs, intestinal wall (ileum), kidney, lymph node, skeletal muscle, dura mater and cerebellum of the NSF autopsy case, primarily in vascular walls. Some, but not all, Gd deposits were seen in fibrotic areas. Literature review highlighted that non-specific tissue fibrosis and calcification are frequent findings in tissues of patients with CRF with and without NSF.
Vascular and extracellular Gd deposits are found in multiple organs of NSF patients, associated with calcification, and often in fibrotic areas. Gd deposits are not seen in patients with CRF unexposed to GBCAs but rarely may be seen in GBCA-exposed patients without clinical signs of NSF. Apart from diagnostic findings in skin, fibrosis of muscle and dura may be more prominent in NSF patients. Our findings should stimulate further investigation of mechanisms of fibrosis and pathologic calcification.
肾源性系统性纤维化（NSF）是一种严重肾功能不全患者的全身性疾病，这些患者曾接受过钆（Gd）基磁共振对比剂（GBCA）治疗。Gd 在 NSF 患者的各种组织中均有发现，主要以大量化学物质的形式存在，这一发现进一步证实了 Gd 暴露与该病之间的因果关联。此前，尚未有关于 Gd 在皮肤以外器官的组织学水平分布的报道。
我们通过光镜和扫描电子显微镜/能量色散 X 射线光谱分析，对经证实患有晚期 NSF 的尸检病例进行组织分析。此外，我们还查阅了已发表的文献，以比较 NSF 患者和无 NSF 的慢性肾衰竭（CRF）患者的组织学和组织化学发现。
在 NSF 尸检病例的皮肤、肝脏、肺部、肠壁（回肠）、肾脏、淋巴结、骨骼肌、硬脑膜和小脑中，均检测到不溶性 Gd-磷酸盐沉积物，主要位于血管壁。并非所有 Gd 沉积物都出现在纤维化区域，但有些出现在纤维化区域。文献综述强调，非特异性组织纤维化和钙化是伴有或不伴有 NSF 的 CRF 患者组织中常见的发现。
在 NSF 患者的多个器官中均发现血管和细胞外 Gd 沉积物，与钙化有关，且常出现在纤维化区域。未接触 GBCA 的 CRF 患者的组织中未观察到 Gd 沉积物，但在接触 GBCA 且无 NSF 临床症状的患者中偶尔可能观察到。除了皮肤的诊断发现外，肌肉和硬脑膜的纤维化可能在 NSF 患者中更为突出。我们的研究结果应促使人们进一步研究纤维化和病理性钙化的发病机制。
