PDF(Pubmed)
Abstract：
Tuberous sclerosis complex (TSC) is an autosomal dominant disease characterized by the development of hamartomas in the central nervous system, heart, skin, lungs, and kidneys and other manifestations including seizures, cortical tubers, radial migration lines, autism and cognitive disability. The disease is associated with pathogenic variants in the TSC1 or TSC2 genes, resulting in the hyperactivation of the mTOR pathway, a key regulator of cell growth and metabolism. Consequently, the hyperactivation of the mTOR pathway leads to abnormal tissue proliferation and the development of solid tumors. Kidney involvement in TSC is characterized by the development of cystic lesions, renal cell carcinoma and renal angiomyolipomas, which may progress and cause pain, bleeding, and loss of kidney function. Over the past years, there has been a notable shift in the therapeutic approach to TSC, particularly in addressing renal manifestations. mTOR inhibitors have emerged as the primary therapeutic option, whereas surgical interventions like nephrectomy and embolization being reserved primarily for complications unresponsive to clinical treatment, such as severe renal hemorrhage. This review focuses on the main clinical characteristics of TSC, the mechanisms underlying kidney involvement, the recent advances in therapy for kidney lesions, and the future perspectives.
摘要：
结节性硬化症（TSC）是一种常染色体显性疾病，其特征是中枢神经系统错构瘤的发展，心,皮肤,肺,肾脏和其他表现，包括癫痫发作，皮质块茎，径向迁移线，自闭症和认知障碍。该疾病与TSC1或TSC2基因的致病变异有关，导致mTOR通路的过度激活，细胞生长和新陈代谢的关键调节剂。因此,mTOR通路的过度激活导致异常的组织增殖和实体瘤的发展。肾脏受累于TSC的特点是囊性病变的发展，肾细胞癌和肾血管平滑肌脂肪瘤，可能会进展并引起疼痛，出血,肾功能丧失.在过去的几年里,TSC的治疗方法发生了明显的转变，特别是在解决肾脏表现。mTOR抑制剂已成为主要的治疗选择，而像肾切除术和栓塞术这样的手术干预措施主要用于对临床治疗无反应的并发症，如严重的肾出血。本文就TSC的主要临床特点进行综述,肾脏受累的潜在机制，肾脏病变治疗的最新进展，和未来的前景。
