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Cystic kidney disease in tuberous sclerosis complex: current knowledge and unresolved questions

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Abstract

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder with an estimated incidence of one in 5000 to 10,000 live births worldwide. Two million people of all races and genders are estimated to have TSC secondary to mutations in one of two tumor suppressor genes, TSC1 or TSC2. The respective TSC1 and 2 gene products — hamartin and tuberin — form cytoplasmic heterodimers that inhibit mTOR-mediated cell growth and division. When mTOR inhibition is lost, people with TSC develop characteristic and usually benign tumors in various organ systems. Kidney tumors and cysts are common, particularly in the setting of TSC2 gene mutations. In most TSC patients, the number of kidney cysts is limited, their morphology is simple, their size is small, and their clinical significance is negligible. In some, cyst morphology progresses from simple to complex with the risk of malignant transformation. In others, aggressive accumulation and growth of kidney cysts can cause hypertension, impaired kidney function, and progression to kidney failure. This educational review summarizes current knowledge and remaining open questions regarding cystic kidney disease in TSC, emphasizing detection, classification, surveillance, and treatment options.

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Abbreviations

ADPKD:

Autosomal dominant polycystic kidney disease

AML:

Angiomyolipoma

CGS:

Contiguous gene syndrome

CKD:

Chronic kidney disease

KF:

Kidney failure

LAM:

Lymphangioleiomyomatosis

mTOR:

Mammalian target of rapamycin

mTORc1:

MTOR complex 1

PC-1:

Polycystin-1

PKD:

Polycystic kidney disease

RHEB:

Ras homolog enriched in brain

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Authors and Affiliations

  1. Department of Radiology, Massachusetts General Hospital, Boston, MA, USA

    Sebastian Gallo-Bernal, Aoife Kilcoyne & Michael S. Gee

  2. Department of Radiology, Harvard Medical School, Boston, MA, USA

    Sebastian Gallo-Bernal, Aoife Kilcoyne & Michael S. Gee

  3. Department of Pediatric Nephrology, Massachusetts General Hospital, Boston, MA, USA

    Elahna Paul

  4. Department of Pediatrics, Harvard Medical School, Boston, MA, USA

    Elahna Paul

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1. c; 2. b; 3. d; 4. a; 5. c

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Gallo-Bernal, S., Kilcoyne, A., Gee, M.S. et al. Cystic kidney disease in tuberous sclerosis complex: current knowledge and unresolved questions. Pediatr Nephrol 38, 3253–3264 (2023). https://doi.org/10.1007/s00467-022-05820-x

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