In the past decade, our understanding of the role of podocytes in the function of the glomerular filtration barrier, and of the role of podocyte injury in the pathogenesis of proteinuric kidney disease, has substantially increased. Landmark genetic studies identified mutations in genes expressed by podocytes as a cause of albuminuria and nephrotic syndrome, leading to breakthrough discoveries from many laboratories. These discoveries contributed to a dramatic change in our view of the glomerular filtration barrier of the kidney and of the role of podocyte injury in the development of albuminuria and progressive kidney disease. In the past several years, studies have demonstrated that podocyte injury is a major cause of marked albuminuria and nephrotic syndrome, and have confirmed that podocytes are important for the maintenance of an intact glomerular filtration barrier. An essential role of loss of these cells in the pathogenesis of glomerulosclerosis and progressive proteinuric kidney disease has also been identified. In this Review, we discuss the importance of podocytes for the maintenance of an intact glomerular filtration barrier and their role in albumin handling.
Podocytes are highly dynamic, terminally differentiated cells that interact with the glomerular basement membrane (GBM) and communicate through signalling at the slit diaphragm
The glomerular filtration barrier is composed of podocytes, the GBM and endothelial cells; damage to any of these layers might result in albuminuria
Podocyte integrity is essential for maintenance of an intact glomerular filtration barrier and podocyte injury is a major cause of marked albuminuria
Several pathogenic mechanisms that are involved in podocyte injury lead to ultrastructural changes in podocytes (that is, podocyte foot process effacement) and proteinuria
In the past few years, exciting advances in technology have enabled visualization of the ultrastructure of living podocytes
These advances have paved the way for an entirely new field of research aimed at understanding the mechanisms of podocyte foot process effacement
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The authors' work is supported by the Deutsche Forschungsgemeinschaft (Sonderforschungsbereich 635 [T. Benzing] and BR2955 [P. T. Brinkkoetter]). Podocyte research has benefited from the contribution of many groups all over the world and we apologize to those colleagues whose work could not be cited due to space limitations.
T. Benzing has received speaker's honoraria from Amgen, Hexal, Novartis and Otsuka. The other authors declare no competing interests.
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Brinkkoetter, P., Ising, C. & Benzing, T. The role of the podocyte in albumin filtration. Nat Rev Nephrol 9, 328–336 (2013). https://doi.org/10.1038/nrneph.2013.78
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