Tuberous sclerosis complex renal disease

Abstract

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.

Tuberous Sclerosis Complex: new criteria for diagnostic work-up and management

“…The response to angiotensin-converting-enzyme inhibitors (ACE inhibitors) and angiotensin receptor blockers is very good. However, concomitant use of ACE inhibitors and mTOR inhibitors has been reported to minimize the effect of the mTOR inhibitor and increase the risk of angioedema [49][50][51].…”

Cystic Kidney Disease: A Primer

“…Renal cystic disease is a significant risk factor for hypertension in this population and responds well to angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. 47 Abdominal MRI should be obtained annually to monitor size and progression of renal angiomyolipomata. Based on the 2012 International Tuberous Sclerosis Consensus Group recommendations, asymptomatic AMLs larger than 3 cm should be treated with an mTOR inhibitor as first-line therapy.…”

Long-Term Everolimus Treatment in Individuals With Tuberous Sclerosis Complex: A Review of the Current Literature

“…18,19 The most common manifestations of TSC to affect the kidneys are angiomyolipomas and renal cysts. 20,21 Up to 80% of patients with TSC will develop an angiomyolipoma at some point in their lives, and renal cysts occur in approximately 50% of patients with TSC. 20,21 An angiomyolipoma larger than 4 cm in diameter can be associated with life-threatening hemorrhage as a result of aneurysms, and larger angiomyolipomas may compress normal kidney tissue, leading eventually to kidney failure.…”

“…20,21 Up to 80% of patients with TSC will develop an angiomyolipoma at some point in their lives, and renal cysts occur in approximately 50% of patients with TSC. 20,21 An angiomyolipoma larger than 4 cm in diameter can be associated with life-threatening hemorrhage as a result of aneurysms, and larger angiomyolipomas may compress normal kidney tissue, leading eventually to kidney failure. 22,23 Angiomyolipomas are also often associated with lymphangioleiomyomatosis, a lung disease found almost exclusively in women.…”

“…A small percentage of TSC patients may have early-onset polycystic phenotype due deletions involving adjacent TSC2 and PKD1 genes on chromosome 16p13. 21 Many patients with TSC (w34%) develop cardiac rhabdomyomas, which are usually detected in childhood with spontaneous regression rate of about 31%. 24 Diagnosis of TSC is usually based on clinical examination using the consensus diagnostic criteria of major and minor disease features, which has recently been updated by the International Tuberous Sclerosis Complex Consensus Group (Table 1).…”