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Roles for urothelium in normal and aberrant urinary tract development

Nature Reviews Urology volume 17, pages 459–468 (2020)Cite this article

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Abstract

Congenital anomalies of the kidney and urinary tract (CAKUTs) represent the leading cause of chronic kidney disease and end-stage kidney disease in children. Increasing evidence points to critical roles for the urothelium in the developing urinary tract and in the genesis of CAKUTs. The involvement of the urothelium in patterning the urinary tract is supported by evidence that CAKUTs can arise as a result of abnormal urothelial development. Emerging evidence indicates that congenital urinary tract obstruction triggers urothelial remodelling that stabilizes the obstructed kidney and limits renal injury. Finally, the diagnostic potential of radiological findings and urinary biomarkers derived from the urothelium of patients with CAKUTs might aid their contribution to clinical care.

Key points

  • Interactions between the developing urothelium and its underlying mesenchyme serve critical roles in developmental patterning of the bladder and ureter.

  • Genetic disruption of signalling pathways that mediate terminal differentiation of urothelium and urothelial–mesenchymal interactions results in phenotypes of congenital abnormalities of the urinary tract in humans and mice.

  • The urothelial plaque serves a critical protective role in response to congenital urinary tract obstruction.

  • Urothelium-specific radiological and biochemical markers represent potential means of detecting congenital abnormalities of the urinary tract, but prospective studies are warranted to evaluate their diagnostic accuracy.

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Fig. 1: Structural properties of urothelium.
Fig. 2: Urothelial–stromal crosstalk serves essential roles in urinary tract development.
Fig. 3: Intrarenal urothelial remodelling in the setting of congenital urinary tract obstruction.

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Acknowledgements

The authors’ research work is supported by National Institutes of Health grants F32DK115085 (A.R.J.), K08-DK122119 (C.B.C.), R01DK085242 (K.M.M.), K08-DK102594 (B.B.) and R01-DK125469 (B.B.). B.B. is also supported by a Norman Siegel Research Scholar Grant from the American Society of Nephrology Foundation for Kidney Research.

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Authors and Affiliations

  1. Nephrology and Urology Research Affinity Group, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH, USA

    Ashley R. Jackson, Christina B. Ching, Kirk M. McHugh & Brian Becknell

  2. Center for Clinical and Translational Research, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH, USA

    Ashley R. Jackson, Christina B. Ching, Kirk M. McHugh & Brian Becknell

  3. Division of Pediatric Urology, Department of Surgery, The Ohio State University College of Medicine, Columbus, OH, USA

    Christina B. Ching

  4. Department of Anatomy, The Ohio State University College of Medicine, Columbus, OH, USA

    Kirk M. McHugh

  5. Nephrology Division, Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, USA

    Brian Becknell

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  3. Kirk M. McHugh
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  4. Brian Becknell
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All authors researched data for the article, wrote the draft, participated in discussions of its content and reviewed and/or edited the manuscript before submission.

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Correspondence to Brian Becknell.

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Nature Reviews Urology thanks C. Mendelsohn and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Jackson, A.R., Ching, C.B., McHugh, K.M. et al. Roles for urothelium in normal and aberrant urinary tract development. Nat Rev Urol 17, 459–468 (2020). https://doi.org/10.1038/s41585-020-0348-2

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