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Kidney damage in tuberous sclerosis
https://doi.org/10.21508/1027-4065-2025-0-5-21-28
Abstract
Tuberous sclerosis is a rare genetic disease characterized by the development of benign tumors in various organs, including the kidneys. Renal lesions in tuberous sclerosis are most often represented by angiomyolipomas and cysts, which can lead to various complications, such as bleeding, renal failure and malignant transformation. This review article examines current concepts of the pathogenesis, clinical manifestations, diagnostics and treatment methods of renal lesions in tuberous sclerosis, as well as prospects for further research in this area.
Supporting agencies: The work was carried out within the framework of the State Assignment “Clinical and molecular genetic criteria for predicting the effectiveness of targeted therapy for kidney damage in tuberous sclerosis in children”. № 1024022200001–0–3.2.3;3.2.20 dated April 1, 2025.
About the Authors
S. L. Morozov
Veltischev Research and Clinical Institute for pediatrics and pediatric surgery; Pirogov Russian National Research Medical University
Russian Federation
Russian Federation
125412, Moscow; 117513, Moscow
O. R. Piruzieva
Veltischev Research and Clinical Institute for pediatrics and pediatric surgery
Russian Federation
Russian Federation
125412, Moscow
L. S. Prikhodina
Veltischev Research and Clinical Institute for pediatrics and pediatric surgery; Russian Medical Academy of Continuous Professional Education
Russian Federation
Russian Federation
125412, Moscow; 125993, Moscow
References
1. Borkowska J., Schwartz R.A., Kotulska K., Jozwiak S. Tuberous sclerosis complex: tumors and tumorigenesis. Int J Dermatol. 2011; 50(1): 13–20. DOI: 10.1111/j.1365-4632.2010.04727.x
2. Huang J., Manning B.D. The TSC1-TSC2 complex: a molecular switchboard controlling cell growth. Biochem J. 2008; 412(2): 179–190. DOI: 10.1042/BJ20080281
3. Morozov S.L., Piruziyeva O.R., Dorofeyeva M.Yu., Tarasova O.V., Dlin V.V. Renal angiomyolipomas in children with tuberous sclerosis — the current state of the problem. Prakticheskaya Meditsina. 2022; 20(2): 45–49. (in Russ) DOI: 10.32000/2072-1757-2022-2-45-49
4. Curatolo P., Bombardieri R., Jozwiak S. Tuberous sclerosis. The Lancet. 2008; 372(9639):657–668. DOI: 10.1016/S0140-6736(08)61279-9
5. Northrup H., Krueger D., Northrup H., Krueger D.A., Roberds S., Smith K., et al. Tuberous Sclerosis Complex Diagnostic Criteria Update: Recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference. Pediatric Neurology 2013; 49(4): 243–254. DOI: 10.1016/j.pediatrneurol.2013.08.001
6. van Slegtenhorst M., de Hoogt R., Hermans C., Nellist M., Janssen B., Verhoef S., et al. Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34. Science. 1997; 277(5327):805–808. DOI: 10.1126/science.277.5327.805
7. Northrup H., Aronow M.E., Bebin E.M., Bissler J., Darling T.N., de Vries P.J., et al. Updated International Tuberous Sclerosis Complex Diagnostic Criteria and Surveillance and Management Recommendations. Pediatr Neurol. 2021; 123: 50–66. DOI: 10.1016/j.pediatrneurol.2021.07.011
8. O’Callaghan F.J., Noakes M.J., Martyn C.N., Osborne J.P. An epidemiological study of renal pathology in tuberous sclerosis complex. BJU Int. 2004; 94(6): 853–857. DOI: 10.1111/j.1464-410X.2004.05046.x
9. Martignoni G., Pea M., Rocca P.C., Bonetti F. Renal pathology in the tuberous sclerosis complex. Pathology. 2003; 35(6): 505–512. DOI: 10.1080/00313020310001619136
10. Zöllner J.P., Franz D.N., Hertzberg C., Nabbout R., Rosenow F., Sauter M., et al. A systematic review on the burden of illness in individuals with tuberous sclerosis complex (TSC). Orphanet J Rare dis. 2020; 15(1): 23. DOI: 10.1186/s13023-019-1258-3
11. Bissler J.J., Kingswood J.C. Optimal treatment of tuberous sclerosis complex associated renal angiomyolipomata: a systematic review. Ther Adv Urol. 2016; 8(4): 279–290. DOI: 10.1177/1756287216641353
12. Mekahli D., Müller R-U., Marlais M., Wlodkowski T., Haeberle S., De Argumedo M.L., et al. Clinical practice recommendations for kidney involvement in tuberous sclerosis complex: a consensus statement by the ERKNet Working Group for Autosomal Dominant Structural Kidney Disorders and the ERA Genes & Kidney Working Group. Nat Rev Nephrol. 2024; 20(6): 402–420. DOI: 10.1038/s41581-024-00818-0
13. Stillwell T.J., Gomez M.R., Kelalis P.P. Renal lesions in tuberous sclerosis. J Urol. 1987; 138(3): 477–481. DOI: 10.1016/s0022-5347(17)43234-4
14. Podolnaya M.A., Kobrinsky B.A., Belousova E.D., Dorofeeva M.Yu., Pivovarova (Goreiko) A.M. Tuberous sclerosis patient registry RU 2017620527. 2017 (in Russ)
15. Altunina G.E., Balayan I.G., Belousova E.D., Bereznitskaya V.V., Bozhko O.V., Verchenko E.G. et al. Tuberous sclerosis. Diagnosis and treatment. Adare. 2017: 288 (in Russ)
16. Morozov S.L., Piruziyeva O.R., Dorofeyeva M.YU., Katysheva O.V., Tarasova O.V., Sakharova Y.S., et al. Problems of polycystic kidney disease in children with tuberous sclerosis at the present stage. Meditsinskiy Opponent. 2022;(3 (19)):45–50 (in Russ);
17. Kingswood J.C., d’Augères G.B., Belousova E., Ferreira J.C., Carter T., Castellana R. et al. TuberOus SClerosis registry to increase disease Awareness (TOSCA) — baseline data on 2093 patients. Orphanet J Rare Dis. 2017; 12: 2. DOI: 10.1186/s13023-016-0553-5
18. Rouvière O., Nivet H., Grenier N., Zini L., Lechevallier E. Kidney damage due to tuberous sclerosis complex: management recommendations. Diagn Interv Imaging. 2013; 94(3): 225–237. DOI: 10.1016/j.diii.2013.01.003
19. Bains L., Bhatia R., Lal P., Bhagria G. Giant bilateral angiomyolipoma of the kidney. Ann R Coll Surg Engl. 2021. 103(6):e184-e188. DOI: 10.1308/rcsann.2020.7036
20. Dabora S.L., Jozwiak S., Franz D.N., Roberts P.S., Nieto A., Chung J. et al. Mutational analysis in a cohort of 224 tuberous sclerosis patients indicates increased severity of TSC2, compared with TSC1, disease in multiple organs. Am J Hum Genet. 2001; 68(1): 64–80. DOI: 10.1086/316951
21. Budde K., Gaedeke J. Tuberous Sclerosis Complex–Associated Angiomyolipomas: Focus on mTOR Inhibition. American Journal of Kidney Diseases. 2012; 59(2): 276–283. DOI: 10.1053/j.ajkd.2011.10.013
22. Kingswood J.C., Belousova E., Benedik M.P., Carter T., Cottin V., Curatolo P. et al. Renal angiomyolipoma in patients with tuberous sclerosis complex: findings from the TuberOus SClerosis registry to increase disease Awareness. Nephrol Dial Transplant. 2019; 34(3): 502–508. DOI: 10.1093/ndt/gfy063
23. Johnson S.R., Cordier J.F., Lazor R., Cottin V., Costabel U., Harari S. et al. European Respiratory Society guidelines for the diagnosis and management of lymphangioleiomyomatosis. Eur Respir J. 2010; 35(1): 14–26. DOI: 10.1183/09031936.00076209
24. Muller A., Rouvière O. Renal artery embolization—indications, technical approaches and outcomes. Nat Rev Nephrol. 2015; 11(5): 288–301. DOI: 10.1038/nrneph.2014.231
25. Krueger D.A., Northrup H., Northrup H., Krueger D.A., Roberds S., Smith K. et al. Tuberous Sclerosis Complex Surveillance and Management: Recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference. PediatricNeurology.2013; 49(4): 255–265
26. Siroky B.J., Czyzyk-Krzeska M.F., Bissler J.J. Renal involvement in tuberous sclerosis complex and von Hippel-Lindau disease: shared disease mechanisms? Nat Clin Pract Nephrol. 2009; 5(3): 143–156. DOI: 10.1038/ncpneph1032
27. Henderson R.J., Germany R., Peavy P.W., Eastham J.A., Venable D.D. Fat density in renal cell carcinoma: demonstration with computerized tomography. J Urol. 1997; 157(4): 1347–1348
28. Morozov S.L., Piruziyeva O.R., Dlin V.V. Efficiency of targeted therapy for kidney damage in tuberous sclerosis in a child (clinical case). Nefrologiya. 2021; 25(4): 90–94. (in Russ). DOI: 10.36485/1561-6274-2021-25-4-90-94
29. Napolioni V., Moavero R., Curatolo P. Recent advances in neurobiology of Tuberous Sclerosis Complex. Brain and Development. 2009; 31(2): 104–113. DOI: 10.1016/j.brain-dev.2008.09.013
30. Siroky B.J., Yin H., Bissler J.J. Clinical and Molecular Insights into Tuberous Sclerosis Complex Renal Disease. Pediatr Nephrol. 2011; 26(6): 839–852. DOI: 10.1007/s00467-010-1689-5
31. Magaki S.D., Vinters H.V. Tuberous Sclerosis Complex. In: Developmental Neuropathology. Editors Adle-Biassette H., Harding B.N., Golden J. Wiley; 2018; 117–131
32. Ignatova M.S. Kidney cysts in children from the standpoint of ciliopathies. Pediatriya. Zhurnal im. G.N. Speranskogo. 2012; 91(3): 110–116 (in Russ)
33. Kleymenova E., Ibraghimov-Beskrovnaya O., Kugoh H., Everitt J., Xu H., Kiguchi K., et al. Tuberin-Dependent Membrane Localization of Polycystin-1. Molecular Cell. 2001; 7(4): 823–832. DOI: 10.1016/S1097-2765(01)00226-X
34. Kingswood J.C., Belousova E., Benedik M.P., Carter T., Cottin V., Curatolo P. et al. Renal Manifestations of Tuberous Sclerosis Complex: Key Findings From the Final Analysis of the TOSCA Study Focussing Mainly on Renal Angiomyolipomas. Front. Neurol. 2020; 11: 972. DOI: 10.3389/fneur.2020.00972
35. Nelson C.P., Sanda M.G. Contemporary diagnosis and management of renal angiomyolipoma. J Urol. 2002; 168(4 Pt 1):1315–1325. DOI: 10.1016/S0022-5347(05)64440-0
36. Sooriakumaran P., Gibbs P., Coughlin G., Attard V., Elmslie F., Kingswood C. et al. Angiomyolipomata: challenges, solutions, and future prospects based on over 100 cases treated. BJU Int. 2010; 105(1): 101–106. DOI: 10.1111/j.1464-410X.2009.08649.x
37. Uysal S.P., Şahin M. Tuberous sclerosis: a review of the past, present, and future. Turk J Med Sci. 2020; 50(SI-2):1665–1676. DOI: 10.3906/sag-2002-133
38. Zoncu R., Bar-Peled L., Efeyan A., Wang S., Sancak Y., Sabatini D.M. mTORC1 senses lysosomal amino acids through an inside-out mechanism that requires the vacuolar H(+)-AT-Pase. Science. 2011; 334(6056):678–683. DOI: 10.1126/science.1207056
39. Franz D.N., Belousova E., Sparagana S., Bebin E.M., Frost M., Kuperman R. et al. Everolimus for subependymal giant cell astrocytoma in patients with tuberous sclerosis complex: 2-year open-label extension of the randomised EXIST-1 study. Lancet Oncol. 2014; 15(13): 1513–1520. DOI: 10.1016/S1470-2045(14)70489-9
40. Bissler J.J., Kingswood J.C., Radzikowska E., Zonnenberg B.A., Frost M., Belousova E. et al. Everolimus for angiomyolipoma associated with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis (EXIST-2): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet. 2013; 381(9869):817–824. DOI: 10.1016/S0140-6736(12)61767-X
41. Bissler J.J., Budde K., Sauter M., Franz D.N., Zonnenberg B.A., Frost M.D. et al. Effect of everolimus on renal function in patients with tuberous sclerosis complex: evidence from EXIST-1 and EXIST-2. Nephrol Dial Transplant. 2019; 34(6): 1000–1008. DOI: 10.1093/ndt/gfy132
42. Janssens P., Van Hoeve K., De Waele L., De Rechter S., Claes K.J., Van de Perre E. et al. Renal progression factors in young patients with tuberous sclerosis complex: a retrospective cohort study. Pediatr Nephrol. 2018; 33(11): 2085–2093. DOI: 10.1007/s00467-018-4003-6
43. Skrzypczyk P., Wabik A.M., Szyszka M., Józwiak S., Bombiński P., Jakimów-Kostrzewa A. et al. Early Vascular Aging in Children With Tuberous Sclerosis Complex. Front Pediatr. 2021; 9: 767394. DOI: 10.3389/fped.2021.767394
44. Massella L., Mekahli D., Paripović D., Prikhodina L., Godefroid N., Niemirska A. et al. Prevalence of Hypertension in Children with Early-Stage ADPKD. Clin J Am Soc Nephrol. 2018; 13(6): 874–883. DOI: 10.2215/CJN.11401017
45. Sugiura H., Shimada T., Moriya-Ito K., Goto J-I., Fujiwara H., Ishii R. et al. A Farnesyltransferase Inhibitor Restores Cognitive Deficits in Tsc2+/– Mice through Inhibition of Rheb1. J. Neurosci. 2022; 42(12): 2598–2612. DOI: 10.1523/JNEU-ROSCI.0449-21.2022
46. Muroga C., Yokoyama H., Kinoshita R., Fujimori D., Yamada Y., Okanishi T. et al. A child with TSC2/PKD1 contiguous gene deletion syndrome successfully treated with tolvaptan for rapidly enlarging renal cysts. CEN Case Rep. 2024; 13(5): 351–355. DOI: 10.1007/s13730-024-00854-6
Review
For citations:
Morozov S.L., Piruzieva O.R., Prikhodina L.S. Kidney damage in tuberous sclerosis. Rossiyskiy Vestnik Perinatologii i Pediatrii (Russian Bulletin of Perinatology and Pediatrics). 2025;70(5):21-28. (In Russ.) https://doi.org/10.21508/1027-4065-2025-0-5-21-28
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