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

Monich, Aline Grosskopf; Bissler, John J.; Barreto, Fellype Carvalho

doi:10.1590/2175-8239-JBN-2024-0013en

Aline Grosskopf Monich

performed the analyses

collected data

wrote the letter

approved the final version

Universidade Federal do Paraná, Departamento de Clínica Médica, Programa de Pós-Graduação em Medicina Interna e Ciências da Saúde, Curitiba, PR, Brazil.

Hospital Universitário Evangélico Mackenzie, Serviço de Nefrologia, Curitiba, PR, Brazil.

https://orcid.org/0000-0002-7256-6674

John J. Bissler

performed the analyses

collected data

wrote the letter

approved the final version

University of Tennessee, Health Science Center, Le Bonheur Children's Hospital, Department of Pediatrics, Memphis, TN, USA.

Le Bonheur Children's Hospital, Children's Foundation Research Institute, Memphis, TN, USA.

St. Jude Children’s Research Hospital, Pediatric Medicine Department, Memphis, TN, USA.

https://orcid.org/0000-0001-9685-9183

Fellype Carvalho Barreto

performed the analyses

collected data

wrote the letter

approved the final version

Universidade Federal do Paraná, Departamento de Clínica Médica, Programa de Pós-Graduação em Medicina Interna e Ciências da Saúde, Curitiba, PR, Brazil.

Universidade Federal do Paraná, Departamento de Clínica Médica, Serviço de Nefrologia, Curitiba, PR, Brazil.

https://orcid.org/0000-0002-6394-9227

Correspondence to: Fellype Carvalho Barreto. Email: fellype.barreto@ufpr.br

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

Authors’ Contributions

AGM, JJB and FCB performed the analyses, collected data, wrote the letter and approved the final version that was sent to the Brazilian Journal of Nephrology.

Genetic criteria^* * Identification of a clearly pathogenic genetic mutation that prevents protein synthesis and/or inactivates the function of the TSC1 or TSC2 proteins; other variants should be evaluated with caution. Presence of a pathogenic variant in TSC1 or TSC2
Clinical criteria Two major criteria or one major and two minor criteria required
Major criteria	Minor criteria
Angiofibromas (≥ 3) or cephalic fibrous plaque	Dental enamel pits (≥ 3)
Ungueal fibromas (≥ 2)	Intraoral fibromas (≥ 2)
Hypomelanotic macules (≥ 3, at least 5 mm in diameter)	Nonrenal hamartoma
Shagreen patch	Retinal achromic patch
Multiple retinal hamartomas	Multiple renal cysts
Multiple cortical tubers and/or radial migration lines	“Confetti” skin lesions
Subependymal nodules (≥ 2)	Sclerotic bone lesions
Subependymal giant cell astrocytomas
Renal angiomyolipomas (≥ 2)^ The combination of angiomyolipomas and lymphagioleiomyomatosis without other findings does not meet the diagnostic criteria.
Cardiac rhabdomyoma
Lymphangioleiomyomatosis^ The combination of angiomyolipomas and lymphagioleiomyomatosis without other findings does not meet the diagnostic criteria.

	Everolimus	Sirolimus
Infectious	Upper respiratory tract, urinary tract infection, pneumonia	Upper respiratory tract, pneumonia, cellulitis, urinary infection
Hematological	Leukopenia, anemia	Leukopenia, anemia
Metabolic	Dyslipidemia, hypophosphatemia	Dyslipidemia, hypokalemia
Neurological	Headache, seizure	Headache, dizziness, tremor
Gastrointestinal	Stomatitis, abdominal pain, nausea, vomiting	Stomatitis, diarrhea, nausea, and abdominal pain
Dermatological	Acne, eczema	Acne, folliculitis
Gynecological	Amenorrhea, menstrual irregularity	Amenorrhea, menstrual irregularity
General	Arthralgia, fatigue	Peripheral edema, fatigue
Laboratorial	Increase in LDH	Increased LDH, AST, and ALT
Renal	Proteinuria	Proteinuria
Cardiac		Tachycardia, high blood pressure

Diagnosis and follow-up
Blood pressure control	Carry out follow-up according to current guidelines since the TSC diagnosis. Give preference to the use of ACEI/ARB.
eGFR	At least once a year
Proteinuria	At least once a year
Imaging exam (preferably MRI)	Perform when TSC is diagnosed or suspected to aid in diagnostic confirmation. Repeat every 1 to 3 years to assess growth and progression of the lesions.
Angiomyolipomas management
Asymptomatic patients with angiomyolipomas < 3 cm in diameter	Follow-up
Asymptomatic patients, > 18 years old, with angiomyolipomas > 3 cm in diameter	First-line therapy: mTOR inhibitors. Monitor dose according to adverse effects and serum level. Therapeutic options: partial nephrectomy and selective arterial embolization
Angiomyolipomas with acute bleeding	First-line therapy: arterial embolization followed by systemic corticotherapy for 7 days (to avoid post-embolization syndrome). If possible, avoid nephrectomy.
Renal replacement therapy at the TSC
RRT modality	All modalities can be used. Consider maintaining the use of mTOR inhibitors for dialysis patients to prevent angiomyolipomas bleeding in native kidneys and, if necessary, control other manifestations of the disease.
Kidney transplant	Consider the use of mTOR inhibitors in the immunosuppressive regimen, also to prevent angiomyolipomas bleeding in native kidneys and, if necessary, to control other manifestations of the disease. Consider nephrectomy of native kidneys depending on kidney size and angiomyolipomas due to risk of bleeding.

[1] Correspondence to: Fellype Carvalho Barreto. Email: fellype.barreto@ufpr.br

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

Abstract