Open AccessReview of the Tuberous Sclerosis Renal Guidelines from the 2012 Consensus Conference: Current Data and Future Study
Author(s) -
J. Chris Kingswood,
John J. Bissler,
Klemens Budde,
John C. Hulbert,
Lisa M. GuayWoodford,
Julian R. Sampson,
Matthias Sauter,
Jane A. Cox,
Uday Patel,
Frances Elmslie,
Chris Anderson,
Bernard A. Zonnenberg
Publication year - 2016
Publication title -
the nephron journals/nephron journals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.951
H-Index - 72
eISSN - 2235-3186
pISSN - 1660-8151
DOI - 10.1159/000448293
Subject(s) - tuberous sclerosis , medicine , angiomyolipoma , everolimus , sirolimus , lymphangioleiomyomatosis , asymptomatic , kidney disease , pi3k/akt/mtor pathway , nephrology , intensive care medicine , kidney , pathology , apoptosis , biochemistry , chemistry
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.