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New insights into the role of podocytes in proteinuria

Nature Reviews Nephrology volume 5, pages 463–468 (2009)Cite this article

Abstract

Disturbances in many different molecular pathways and interactions can lead to the same clinical end points of proteinuria and end-stage renal disease. Proteinuria is often accompanied by a cytopathological change in the glomerulus that is referred to as effacement (retraction) of the podocyte foot processes. The molecular mechanisms that lead to proteinuria and podocyte effacement are poorly understood; therefore, targeted therapies are lacking. During the past 5 years, however, a large body of data has emerged in this field. The discovery of podocyte gene defects that underlie some hereditary proteinuric syndromes has changed our understanding of the relative contributions of components of the glomerular filter. Furthermore, pathogenic pathways activated in podocytes during proteinuria have been identified. Together, these findings pinpoint the podocyte as the most obvious candidate for therapeutic intervention. In the near future, the use of large-scale expression profiling platforms, transgenic mouse lines, and other in vivo gene delivery methods will further expand our understanding of the pathology of the glomerular filtration barrier, and perhaps reveal novel target molecules for the therapy of proteinuric kidney diseases.

Key Points

  • Although the glomerular endothelium, glomerular basement membrane and podocytes all contribute to the filtration barrier, the podocytes seem to be the most critical part of the filtration unit

  • Most cases of proteinuria are associated with retraction (effacement) of podocyte foot processes, although the mechanisms of this association are not well understood

  • Several pathogenic pathways activated in podocytes during the development of proteinuria have been discovered

  • The use of molecular profiling, transgenic mice and in vivo gene delivery will expand our understanding of the glomerular filtration barrier, and perhaps reveal novel therapeutic targets for proteinuria

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Figure 1: Structure of the glomerular filtration barrier.
Figure 2: Podocyte effacement is a characteristic morphological change associated with proteinuria and nephrotic syndrome, as revealed by scanning electronic micrographs.

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Acknowledgements

The authors' research is supported by The Swedish Medical Research Council (J. Patrakka and K. Tryggvason), The Swedish Society of Medicine (J. Patrakka), and the Knut and Alice Wallenberg Foundation (K. Tryggvason).

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Authors and Affiliations

  1. Department of Renal Medicine, Karolinska University Hospital, Stockholm, Sweden

    Jaakko Patrakka

  2. Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden

    Karl Tryggvason

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Correspondence to Jaakko Patrakka.

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Patrakka, J., Tryggvason, K. New insights into the role of podocytes in proteinuria. Nat Rev Nephrol 5, 463–468 (2009). https://doi.org/10.1038/nrneph.2009.108

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