Renal manifestation of tuberous sclerosis complex

Abstract

Tuberous sclerosis complex (TSC) is a tumor predisposition syndrome with significant renal cystic and solid tumor disease. It commonly causes several types of cystic disease and benign tumors (angiomyolipomata) in the kidneys that can both lead to significant premature loss of glomerular filtration rate. The main risks of angiomyolipomata, severe bleeding, loss of renal function, and pulmonary lymphangioleiomyomatosis, can be ameliorated by active surveillance and preemptive therapy with mTOR inhibitors. The cystogenic mechanism may involve primary cilia, but also appears to also involve a majority of normal tubular cells and may be driven by a minority of cells with mutations inactivating both their TSC1 or TSC2 genes. Malignant tumors are rare.

Tuberous sclerosis complex exhibits a new renal cystogenic mechanism

“…), it is not clear that mTORC1 inhibition is useful for severe forms of TSC renal cystic disease. We examined patients with the focal and cortical cystic variants of TSC (Bissler and Kingswood ) who were on an mTORC1 inhibitor clinically and found that they also respond to mTORC1 inhibitors by reducing their cystic burden (Fig. D and E).…”

Tuberous Sclerosis Complex Axis Controls Renal Extracellular Vesicle Production and Protein Content

“…The majority of TSC patient develop some form of kidney cyst during their life time but the exact mechanism of kidney cystogenesis in tuberous sclerosis complex is unknown [20]. The TSC cystic disease can manifest as one or more of at least five patterns of disease [1], and appears to have a very novel cystogenic mechanism involving the renal tubular cells [14]. In a previous study, we reported that the loss of Tsc2 gene in a mouse renal principal cell affected the phenotype of intercalated cell causing an enhanced mTORC1 activity, thus leading to renal cystogenesis likely via an EV-dependent pathway [14] ( Figure 5).…”

“…More than one million patients world-wide suffer from tuberous sclerosis complex (TSC) and have mutations in either of the tumor suppressor genes, TSC1 or TSC2 [1]. Together, the TSC proteins regulate mTORC1 activity and control cell growth [2], a function critical for organogenesis and organ maintenance [3,4].…”

“…Approximately 40% of patients with TSC experience a premature decline of glomerular filtration rate (GFR) in the absence of angiomyolipomata bleeding or interventions [6]. The loss of renal function is caused by the five different TSC renal cystic disease phenotypes, and angiomyolipomata [1].…”

Selective Arterial Embolization for Large or Symptomatic Renal Angiomyolipoma: 10 Years of Follow-up

“…[2][3][4] Surgical intervention for AML was reportedly more common among TSC, 5 and the prevalence of morbidity and mortality related to renal complications is high even in the setting of preventive arterial embolization. 6,7 Current guidelines for the treatment of AML recommend active surveillance for most cases, with nephronsparing surgery as the treatment of choice in patients with persistent pain or repeated bleeding episodes. 1 Selective arterial embolization (SAE) is considered to have limited value in the long-term, and it is rather recommended in cases involving patients with larger tumors unsuitable for surgery, in order to allow the shrinkage of tumor before surgery, or in an emergency setting such as retroperitoneal bleeding.…”