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  • Review Article
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Renal involvement in tuberous sclerosis complex and von Hippel–Lindau disease: shared disease mechanisms?

Nature Reviews Nephrology volume 5, pages 143–156 (2009)Cite this article

Abstract

Tuberous sclerosis complex and von Hippel–Lindau disease are distinct autosomal dominant tumor suppressor syndromes that can exhibit similar renal phenotypes and seem to share some signaling pathway components. Similarities exist in the current clinical management of, and the newly identified potential therapeutic approaches for, these conditions. This Review summarizes the pathophysiologic and therapeutic overlap between tuberous sclerosis complex and von Hippel–Lindau disease and highlights the results of recent drug trials in these settings.

Key Points

  • Tuberous sclerosis complex (TSC) and von Hippel–Lindau (VHL) disease are distinct tumor suppressor syndromes caused by mutations in the TSC1 and TSC2 genes and in the VHL gene, respectively

  • TSC and VHL disease are both associated with the development of cystic renal disease and vascular tumors, including renal cell carcinoma

  • The similarities between TSC and VHL disease are due in part to overlap in the pathways and functions of the affected genes

  • Physical examinations, imaging studies and laboratory investigations are the cornerstones of follow-up in patients with renal complications of TSC or VHL disease

  • Increased knowledge of the signaling pathways involved in TSC and VHL disease has prompted the initiation of trials to test novel pharmacological interventions

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Figure 1: Regulation of cell growth and proliferation by TSC and VHL genes.
Figure 2: Loss of the tumor suppressor pVHL has a central role in the pathogenesis of renal cell carcinoma via multiple HIF-dependent and HIF-independent signaling pathways.
Figure 3: Rapid growth of renal angiomyolipomas in a child with tuberous sclerosis complex.
Figure 4: PET and CT scans of a patient with type 2 von Hippel–Lindau disease.

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Acknowledgements

This work was supported by NIH Grants DK061458 and DoDTS050008 (to JJ Bissler) and NCI CA122346 and DoDPR064135 (to MF Czyzyk-Krzeska) and by the PKD Foundation (to BJ Siroky). The authors thank Jason Steinberg and Bradley Dixon for their critical reading of the manuscript.

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Authors and Affiliations

  1. BJ Siroky is a Research Fellow in the Division of Nephrology at Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.,

    Brian J Siroky

  2. MF Czyzyk-Krzeska is a Professor in the Department of Cancer and Cell Biology at the Vontz Center for Molecular Studies, University of Cincinnati, Cincinnati, OH, USA.,

    Maria F Czyzyk-Krzeska

  3. JJ Bissler is Professor of Pediatrics and Clark D West Chair of Nephrology at the University of Cincinnati, Cincinnati, OH, USA.,

    John J Bissler

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  1. Brian J Siroky
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  2. Maria F Czyzyk-Krzeska
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Correspondence to John J Bissler.

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Siroky, B., Czyzyk-Krzeska, M. & Bissler, J. Renal involvement in tuberous sclerosis complex and von Hippel–Lindau disease: shared disease mechanisms?. Nat Rev Nephrol 5, 143–156 (2009). https://doi.org/10.1038/ncpneph1032

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