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Review
. 2024 Jul 5;46(3):e20240013.
doi: 10.1590/2175-8239-JBN-2024-0013en. eCollection 2024.

Tuberous Sclerosis Complex and the kidneys: what nephrologists need to know

[Article in English, Portuguese]
Aline Grosskopf Monich  1   2 , John J Bissler  3   4   5 , Fellype Carvalho Barreto  1   6
Affiliations
Review

Tuberous Sclerosis Complex and the kidneys: what nephrologists need to know

[Article in English, Portuguese]
Aline Grosskopf Monich et al. J Bras Nefrol. .

Abstract
in English, Portuguese

Tuberous sclerosis complex (TSC) is an autosomal dominant disease characterized by the development of hamartomas in the central nervous system, heart, skin, lungs, and kidneys and other manifestations including seizures, cortical tubers, radial migration lines, autism and cognitive disability. The disease is associated with pathogenic variants in the TSC1 or TSC2 genes, resulting in the hyperactivation of the mTOR pathway, a key regulator of cell growth and metabolism. Consequently, the hyperactivation of the mTOR pathway leads to abnormal tissue proliferation and the development of solid tumors. Kidney involvement in TSC is characterized by the development of cystic lesions, renal cell carcinoma and renal angiomyolipomas, which may progress and cause pain, bleeding, and loss of kidney function. Over the past years, there has been a notable shift in the therapeutic approach to TSC, particularly in addressing renal manifestations. mTOR inhibitors have emerged as the primary therapeutic option, whereas surgical interventions like nephrectomy and embolization being reserved primarily for complications unresponsive to clinical treatment, such as severe renal hemorrhage. This review focuses on the main clinical characteristics of TSC, the mechanisms underlying kidney involvement, the recent advances in therapy for kidney lesions, and the future perspectives.

Resumo: O complexo da esclerose tuberosa (CET) é uma doença autossômica dominante caracterizada pelo desenvolvimento de hamartomas no sistema nervoso central, coração, pele, pulmões e rins e outras manifestações, incluindo convulsões, tubérculos corticais, linhas de migração radial, autismo e deficiência cognitiva. A doença está associada a variantes patogênicas nos genes TSC1 ou TSC2, resultando na hiperativação da via mTOR, um importante regulador do crescimento e metabolismo celular. Consequentemente, a hiperativação da via mTOR leva à proliferação anormal do tecido e ao desenvolvimento de tumores sólidos. O envolvimento renal no CET é caracterizado pelo desenvolvimento de lesões císticas, carcinoma de células renais e angiomiolipomas renais, que podem progredir e causar dor, sangramento e perda da função renal. Nos últimos anos, houve uma mudança notável na abordagem terapêutica do CET, especialmente no tratamento das manifestações renais. Os inibidores de mTOR surgiram como a principal opção terapêutica, enquanto intervenções cirúrgicas como nefrectomia e embolização são reservadas principalmente para complicações que não respondem ao tratamento clínico, como hemorragia renal grave. Esta revisão se concentra nas principais características clínicas do CET, nos mecanismos subjacentes ao envolvimento renal, nos recentes avanços na terapia para lesões renais e nas perspectivas futuras.

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Conflict of interest statement

Conflict of Interest The authors have no conflict of interest related to this publication.

Figures

Figure 1
Figure 1. Dysfunction of the mTOR pathway and mechanism of action of mTOR inhibitors in tuberous sclerosis complex.
Figure 2
Figure 2. Clinical manifestations of Tuberous Sclerosis Complex.
Figure 3
Figure 3. MRI of a male patient with tuberous sclerosis complexshowing a large angiomyolipoma in the right kidney and a cyst in the left kidney.
Figure 4
Figure 4. MRI showing large renal masses compatible with angiomyolipomas that replace practically the entire renal parenchyma in a patient with tuberous sclerosis complex.
Figure 5
Figure 5. MRI of a female patient with tuberous sclerosis complex and lymphangioleiomyomatosis. Pneumothorax, which is a complication of lymphangioleiomyomatosis, with ipsilateral pulmonary atelectasis is noted.
Figura 1
Figura 1. Disfunção da via mTOR e mecanismo de ação dos inibidores de mTOR no complexo da esclerose tuberosa.
Figura 2
Figura 2. Manifestações clínicas do Complexo Esclerose Tuberosa.
Figura 3
Figura 3. RM de um paciente do sexo masculino com complexo da esclerose tuberosa mostrando um grande angiomiolipoma no rim direito e um cisto no rim esquerdo.
Figura 4
Figura 4. RM mostrando grandes massas renais compatíveis com angiomiolipomas que substituem praticamente todo o parênquima renal em um paciente com complexo da esclerose tuberosa.
Figura 5
Figura 5. RM de uma paciente do sexo feminino com complexo da esclerose tuberosa e linfangioleiomiomatose. Observa-se pneumotórax, uma complicação da linfangioleiomiomatose, com atelectasia pulmonar ipsilateral.
See this image and copyright information in PMC

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