Abstract：
Renal-related disease is the most common cause of tuberous sclerosis complex (TSC)-related death in adults, and renal angiomyolipomas can lead to complications that include chronic kidney disease (CKD) and hemorrhage. International TSC guidelines recommend mammalian target of rapamycin (mTOR) inhibitors as first-line therapy for management of asymptomatic, growing angiomyolipomas >3 cm in diameter. This review discusses data regarding patient outcomes that were used to develop current guidelines for embolization of renal angiomyolipomas and presents recent data on 2 available mTOR inhibitors - sirolimus and everolimus - in the treatment of angiomyolipoma. TSC-associated renal angiomyolipomas can recur after embolization. Both sirolimus and everolimus have shown effectiveness in reduction of angiomyolipoma volume, with an acceptable safety profile that includes preservation of renal function with long-term therapy. The authors propose a hypothesis for mTORC1 haploinsufficiency as an additional mechanism for CKD and propose that preventive therapy with mTOR inhibitors might have a role in reducing the number of angiomyolipoma-related deaths. Because mTOR inhibitors target the underlying pathophysiology of TSC, patients might benefit from treatment of multiple manifestations with one systemic therapy. Based on recent evidence, new guidelines should be considered that support the earlier initiation of mTOR inhibitor therapy for the management of renal angiomyolipomas to prevent future serious complications, rather than try to rescue patients after the complications have occurred.
摘要：
肾脏相关疾病是成人结节性硬化症（TSC）相关死亡的最常见原因，肾血管平滑肌脂肪瘤可导致并发症，包括慢性肾脏疾病（CKD）和出血。国际TSC指南推荐哺乳动物雷帕霉素靶蛋白（mTOR）抑制剂作为无症状治疗的一线治疗，生长的血管平滑肌脂肪瘤直径>3厘米。这篇综述讨论了用于制定当前肾血管平滑肌脂肪瘤栓塞指南的患者预后数据，并介绍了两种可用的mTOR抑制剂西罗莫司和依维莫司治疗血管平滑肌脂肪瘤的最新数据。TSC相关的肾血管平滑肌脂肪瘤在栓塞后可复发。西罗莫司和依维莫司均显示出减少血管平滑肌脂肪瘤体积的有效性，具有可接受的安全性，包括通过长期治疗保留肾功能。作者提出了mTORC1单倍体功能不足作为CKD的额外机制的假设，并提出mTOR抑制剂的预防性治疗可能在减少血管平滑肌脂肪瘤相关死亡的数量中发挥作用。因为mTOR抑制剂靶向TSC的潜在病理生理学,患者可能从一项全身治疗的多种表现中获益.根据最近的证据,应考虑新的指南，支持早期开始mTOR抑制剂治疗肾血管平滑肌脂肪瘤，以预防未来的严重并发症，而不是在并发症发生后试图抢救患者。
