title: Treatment of Renal Angiomyolipoma and Other Hamartomas in Patients with Tuberous Sclerosis Complex.
abstract: Tuberous sclerosis complex is an autosomal dominant genetic disease characterized by growth of benign tumors (hamartomas) in multiple organs, especially the kidneys, brain, heart, lungs, and skin. Tuberous sclerosis complex is usually caused by a mutation in either thetuberous sclerosis complex 1ortuberous sclerosis complex 2gene, resulting in constitutive activation of mammalian target of rapamycin signaling. Currently, mammalian target of rapamycin inhibitors are recommended in adult patients with tuberous sclerosis complex for the treatment of asymptomatic, growing renal angiomyolipoma that are >3 cm in diameter and pediatric or adult patients with brain lesions (subependymal giant cell astrocytoma) that either are growing or are not amenable to surgical resection. Clinical evidence suggests that systemic administration of a mammalian target of rapamycin inhibitor may provide concurrent improvements in multiple lesions and symptoms of tuberous sclerosis complex. With the major paradigm shift in consensus guidelines toward screening at diagnosis and ongoing monitoring and with the recent availability of an effective oral treatment, it is important that nephrologists have a thorough understanding of our role in the management of patients with tuberous sclerosis complex. Because the various manifestations of tuberous sclerosis complex typically emerge at different periods during patients' lifetimes, patients will need to be followed throughout their lives. Unlike brain and cardiac lesions, renal lesions are more likely to emerge as patients age and can grow at any time. Considerations regarding long-term medication administration for the potential control of multiple tuberous sclerosis complex manifestations will need to be addressed; these include the most appropriate starting dose, appropriate doses for tumor shrinkage versus prevention of regrowth, and management of adverse events. Best practices and potential obstacles for nephrologists treating patients with tuberous sclerosis complex who have multiple manifestations are considered.
authors.affiliation: Renal Disease and Hypertension, Pediatric Nephrology and Hypertension, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Texas.
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Samuels
mesh_terms: D018207:Angiomyolipoma / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004621:Embolization, Therapeutic; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D058990:Molecular Targeted Therapy; D009154:Mutation; D009392:Nephrectomy; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D016896:Treatment Outcome; D014402:Tuberous Sclerosis / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D047368:Tumor Burden / Q000187:drug effects; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases
keywords: mTOR; multidisciplinary approach; renal angiomyolipoma; tuberous sclerosis