Clinical and Molecular Insights into Tuberous Sclerosis Complex Renal Disease

Siroky, Brian J.; Yin, Hong; Bissler, John J.

doi:10.1007/s00467-010-1689-5

Cited by 48 publications

(41 citation statements)

References 116 publications

(118 reference statements)

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“…All components of angiomyolipomas, including the vascular cells, immature smooth-muscle-like spindle cells, epithelioid cells, and fat cells contain somatic mutations that, combined with their germline mutation, render the cells deficient in either tuberin or hamartin. Presumably, this deficiency disrupts the integrated control of cell growth leading to the angiomyolipoma [12] . A crosssectional study of TSC patients revealed an increase in angiomyolipomas during childhood and adolescence that then stabilized throughout adulthood [13] .…”

Section: Renal Angiomyolipomas In Tscmentioning

confidence: 99%

Tuberous sclerosis complex renal disease

Dixon¹,

Kingswood²,

Bissler³

2015

Oxford Medicine Online

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and intractable epilepsy), less than 40% of affected patients have all three features [3] . TSC most often presents with neurologic symptoms, and approximately 90% of affected individuals experience seizures and about half of patients experience cognitive impairment, autism, or other behavioral disorders. Renal manifestations are the second most common findings associated with TSC, with angiomyolipomas occurring in 80% and renal cystic disease in ϳ 50% of patients. Pulmonary involvement, specifically lymphangioleiomyomatosis (LAM), is the third most common cause of TSC-associated morbidity, occurring in approximately 35% of female TSC patients. The gender predilection in LAM is not understood.TSC is caused by mutations in either the TSC1 gene, located on chromosome 9, or the TSC2 gene, located on chromosome 16. Typically children with TSC are born with normal kidneys but develop cystic disease and angiomyolipomas as they age. Both renal cystic disease and angiomyolipomas cause chronic kidney disease (CKD), affecting approximately one million patients with TSC worldwide. Renal disease poses a significant burden on patients with TSC because of the relentless progression, morbidity, and mortality of CKD. In fact, using death certificate data Shepherd et al. [4] identified renal failure as the leading cause of death in their adult patients at the Mayo Clinic. Key WordsTuberous sclerosis complex ؒ Angiomyolipoma ؒ Renal cyst ؒ Oncocytoma ؒ Mammalian target of rapamycin complex 1 ؒ Rapamycin ؒ Sirolimus AbstractAlthough not as common as other genetic renal diseases such as autosomal dominant polycystic kidney disease, patients with tuberous sclerosis complex frequently have significant renal involvement. Recent revelations in the cell biology of these renal disease manifestations as well as effective therapies for tuberous sclerosis complex-related renal issues have heralded hope of improved renal survival and improved quality of life for the TSC patient. This review specifically addresses some of the major renal manifestations of this disease.

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Section: Renal Angiomyolipomas In Tscmentioning

confidence: 99%

Tuberous sclerosis complex renal disease

Dixon¹,

Kingswood²,

Bissler³

2015

Oxford Medicine Online

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“…Nowadays, the management of active bleeding from angiomyolipomas consists of arterial embolization, sometimes even prophylactic. Unfortunately, most often unnecessarily, partial or total nephrectomy is still performed [8,28].…”

Section: Angiomyolipomamentioning

confidence: 99%

“…The discovery of human melanoma black-45 (HMB-45) and other melanocytic markers such as melanin-A, has increased the reliability of the biopsies. Virtually all angiomyolipomas stain positive for these antibodies, and RCC stains negative, making immunohistochemistry extremely important in excluding RCC [28].…”

Section: Fat-poor Renal Lesionsmentioning

confidence: 99%

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Tuberous sclerosis complex: the past and the future

2014

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Renal lesions represent the second most significant cause of morbidity and mortality in patients with tuberous sclerosis complex (TSC). Recent advances in the understanding of the pathophysiology of TSC have led to the exploration of new potential therapeutic targets. Clinical trials with mammalian target of rapamycin (mTOR) inhibitors have demonstrated promising results for several indications, such as renal angiomyolipoma, subependymal giant cell astrocytoma, lymphangioleiomyomatosis and facial angiofibromas. Currently, there is a scarcity of natural history data and randomized, placebo-controlled clinical trials on TSC. Recently, however, recommendations for the diagnostic criteria, surveillance, and management of TSC patients have been updated. This review focuses on these novel recommendations and highlights the need for multidisciplinary follow-up of this multi-systemic disease.

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“…According to the relevant literature, TSC may be associated with glial tumors, adenoma sebaceum, rhabdomyoma and hamartomatous tumors of the thyroid, retina, liver, pancreas, lung, kidney, adrenals and ovaries. The clinical manifestations of TSC depend on the target organs, such as the brain, skin, kidneys, lungs and heart, or the organs that are oppressed by the expansion of the lesions (3,9,10).…”

Section: Introductionmentioning

confidence: 99%

Tuberous sclerosis-associated renal angiomyolipoma: A report of two cases and review of the literature

Lin

Jin

et al. 2017

Molecular and Clinical Oncology

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Abstract.In the general population, tuberous sclerosis-associated renal angiomyolipoma (RAML) is a rare benign hamartoma with potentially life-threatening complications and a poor prognosis. The two patients reported in the present study, who were diagnosed with bilateral RAML and spontaneous rupture of the RAML with tuberous sclerosis, presented with flank pain, abdominal pain, hemorrhage, hematuria and multiple lesions. The two cases are representative examples of the disease, and highlight the importance of determining the risk of acute hemorrhage in the early stages, and the significance of timely and proper treatment. IntroductionRenal angiomyolipoma (RAML) is a type of benign hamartoma that may occur sporadically or be associated with tuberous sclerosis complex (TSC) (1-3). It has been reported that the number of sporadic angiomyolipomas is four times that of the cases associated with TSC (3,4). Generally, ~80% of patients with TSC have hamartoma. However, RAML associated with TSC comprises only 0.3% of all renal neoplasms (5). In short, RAML is common in patients with TSC, but rare in the general population (2). Notably, TSC-associated RAMLs are typically bilateral and multifocal, larger, and more likely to lead to potentially life-threatening hemorrhage compared with isolated RAML (1). TSC is a rare autosomal dominant disease with incomplete penetrance; it is characterized by a constellation of findings affecting multiple organ systems, and has a worldwide prevalence of ~1/6,000 to 1/12,000 individuals (2,6-8). According to the relevant literature, TSC may be associated with glial tumors, adenoma sebaceum, rhabdomyoma and hamartomatous tumors of the thyroid, retina, liver, pancreas, lung, kidney, adrenals and ovaries. The clinical manifestations of TSC depend on the target organs, such as the brain, skin, kidneys, lungs and heart, or the organs that are oppressed by the expansion of the lesions (3,9,10).The present study reports two cases of TSC-associated RAML. Case reportsCase one. A 31-year-old woman with a chief complaint of left flank pain and abdominal pain of three months duration was admitted to Peking University Shenzhen Hospital (Shenzhen, China) in March 2016. Laboratory examinations yielded the following results: Red blood cell (RBC) count, 3.59x10 12 /l (normal range, 4.0-5.5x10 12 /l); and hemoglobin (HGB) level, 111 g/l (normal range, 120-160 g/l). Subsequently, a contrast-enhanced computed tomography (CE-CT) scan indicated bilateral multiple renal masses with a large hematoma in the left kidney (Fig. 1A), and no enhancement (Fig. 1B). Additionally, magnetic resonance imaging (MRI) of the brain was performed, revealing multiple swellings of the cortex, with increased signal intensity in the left temporal lobe, parietal lobe, occipital lobe, and two frontal lobes, and a small focal ischemia in the right basal ganglion (Fig. 2). The patient was diagnosed with bilateral RAMLs and spontaneous rupture of the left RAML with TSC, which was temporarily managed conservatively without further interv...

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Clinical and Molecular Insights into Tuberous Sclerosis Complex Renal Disease

Cited by 48 publications

References 116 publications

Tuberous sclerosis complex renal disease

Tuberous sclerosis complex renal disease

Tuberous sclerosis complex: the past and the future

Tuberous sclerosis-associated renal angiomyolipoma: A report of two cases and review of the literature

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