title: Review of the Tuberous Sclerosis Renal Guidelines from the 2012 Consensus Conference: Current Data and Future Study.
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.
authors: Sussex Kidney Unit, Royal Sussex County Hospital, Brighton, UK.
authors: J Chris
authors: JC
authors: Kingswood
authors: John J
authors: JJ
authors: Bissler
authors: Klemens
authors: K
authors: Budde
authors: John
authors: J
authors: Hulbert
authors: Lisa
authors: L
authors: Guay-Woodford
authors: Julian R
authors: JR
authors: Sampson
authors: Matthias
authors: M
authors: Sauter
authors: Jane
authors: J
authors: Cox
authors: Uday
authors: U
authors: Patel
authors: Frances
authors: F
authors: Elmslie
authors: Chris
authors: C
authors: Anderson
authors: Bernard A
authors: BA
authors: Zonnenberg
mesh_terms: D000328:Adult; D018207:Angiomyolipoma / Q000150:complications* / Q000188:drug therapy / Q000401:mortality / Q000503:physiopathology; D032921:Consensus; D006801:Humans; D007680:Kidney Neoplasms / Q000150:complications* / Q000188:drug therapy / Q000401:mortality / Q000503:physiopathology; D017410:Practice Guidelines as Topic; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D014402:Tuberous Sclerosis / Q000150:complications* / Q000401:mortality / Q000503:physiopathology
chemical_list: C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases