From tuberous sclerosis complex to end stage renal disease: who are these patients?

Abstract

In patients with tuberous sclerosis complex (TSC), renal complications are not limited to bleeding angiomyolipoma (AML); although rare, end-stage renal disease (ESRD) may occur. New treatments (e.g. mammalian target of rapamycin (m-Tor) inhibitors) for AML might influence the epidemiology of ESRD in patients with TSC. In France, 99 patients with TSC from the Renal Epidemiology and Information Network (REIN) registry and having undergone renal replacement therapy (RRT) between 2002 and 2016 were included in the present study. Additional data were collected from the patients' medical charts. The mean ± standard deviation age at RRT initiation was 48.4 ± 16.4 and 73.8% had a neurologic impairment. Fifty-four patients underwent kidney transplantation after an average of 23 ± 12.3 months on dialysis. Among the 61 patients with additional data the most common renal lesion was AML: 26.2% of the patients had isolated AML, and 26.2% had AML and renal cysts, 65.6% of patients had undergone nephrectomy, and 16.4% had undergone at least one embolization. None of the patients had been treated with an m-Tor inhibitor before dialysis. The graft survival rate was 92.5% at 5 years and 70.2% at 10 years. The present cohort study is the first to have assessed TSC patients on RRT from a national registry. Nephrectomy or embolization due to AML was the leading cause of ESRD in our cohort. By reducing the size of the AML, m-tor inhibitors might lower the risk of complications and thus reduce the number of patients with TSC requiring RRT.

Updated International Tuberous Sclerosis Complex Diagnostic Criteria and Surveillance and Management Recommendations

“…131 The minority of patients who develop advanced renal failure can still benefit from mTORi therapy to prevent bleeding and to possibly slow or stop decline in renal function. 124 For individuals with TSC, all options for renal replacement therapy should be considered, including those with neurological impairment 132 (Category 2B).…”

Endovascular treatment of intrarenal aneurysms bleeding and angiomyolipomas in a patient with tuberous sclerosis and polycystic kidney disease

“…Tuberous sclerosis complex (TSC) is a rare autosomal dominant neurocutaneous syndrome with involvement of multiple organs such as central nervous system, skin, renal, and lung manifestations. Although first described in the nineteenth century, its links to two suppressor genes (TSC1 and TSC2) were only identified in 1997 [1][2][3] . The prevalence in the general population is 1:12,500, live birth rate is about 1:5,800, and about a million individuals live with this disease 3 .…”

“…Although first described in the nineteenth century, its links to two suppressor genes (TSC1 and TSC2) were only identified in 1997 [1][2][3] . The prevalence in the general population is 1:12,500, live birth rate is about 1:5,800, and about a million individuals live with this disease 3 .…”

“…ADPKD is usually bilateral and may manifest at any age but mostly appears during the fourth and fifth decades. It is also linked to mutations of two genes, PKD1 and PKD2 [1][2][3][4] .…”

The Correlation Between Tuberous Sclerosis Complex Genotype and Renal Angiomyolipoma Phenotype

“…Of note, compared with sporadic RAML, TSC-RAML had an early onset, with bilateral and multiple lesions and faster growth (Rabenou and Charles, 2015). Although most of the RAML patients had no obvious clinical symptoms, a great proportion of patients experience abdominal pain, low blood volume shock, renal insufficiency, or end-stage renal disease which can even lead to mortality (Swärd et al, 2020;Vabret et al, 2020). Overall, RAML is considered to be the major cause of death in TSC patients (Amin et al, 2017).…”