Division of Nephrology, Atlanta Veterans Administration Health Center, Emory University School of Medicine, Atlanta, Georgia, USA.
J Am Acad Dermatol. 2010 Feb;62(2):343-5. doi: 10.1016/j.jaad.2009.04.022.
Nephrogenic systemic fibrosis (NSF) is a fibrosing disorder that occurs in some patients with renal insufficiency. Exposure to gadolinium-based contrast agents (GdCA) has been associated with the development of NSF. No uniformly effective treatment options exist. We present immunohistochemical evidence to show that the proliferating fibrocytes of NSF express phospho-70-s6 kinase (PI-3-K), a protein downstream of PI-3-K, and the target of the drug rapamycin. In our patient, use of rapamycin resulted in rapid clinical improvement marked by reduced edema, reduced skin induration, and decreased pain. This suggests a possible role for PI-3-K and rapamycin (mTOR) pathways in the pathogenesis of NSF. Drugs that inhibit these pathways may be a target for future therapy. While our patient did attribute disease onset to GdCA exposure, used on a single occasion for abdominal imaging, he was also exposed to iron, calcium, and darbepoetin alpha at the time of imaging.
肾源性系统性纤维化（NSF）是一种纤维性疾病，发生于一些肾功能不全的患者。接触钆基造影剂（GdCA）与 NSF 的发生有关。目前尚无统一有效的治疗选择。我们提供免疫组化证据表明，NSF 的增殖成纤维细胞表达磷酸化-70- S6 激酶（PI-3-K），这是 PI-3-K 的下游蛋白，也是药物雷帕霉素的靶点。在我们的患者中，使用雷帕霉素导致了快速的临床改善，表现为水肿减轻、皮肤硬化减轻和疼痛减轻。这表明 PI-3-K 和雷帕霉素（mTOR）途径可能在 NSF 的发病机制中起作用。抑制这些途径的药物可能是未来治疗的靶点。虽然我们的患者确实将疾病发作归因于 GdCA 暴露，但仅在一次腹部成像时使用，但他在成像时也接触了铁、钙和达贝泊汀α。
