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Pediatric Nephrology
Published in: Pediatric Nephrology 3/2017

01-03-2017 | Review

Mechanical challenges to the glomerular filtration barrier: adaptations and pathway to sclerosis

Authors: Wilhelm Kriz, Kevin V. Lemley

Published in: Pediatric Nephrology | Issue 3/2017

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Abstract

Podocytes are lost as viable cells by detachment from the glomerular basement membrane (GBM), possibly due to factors such as pressure and filtrate flow. Distension of glomerular capillaries in response to increased pressure is limited by the elastic resistance of the GBM. The endothelium and podocytes adapt to changes in GBM area. The slit diaphragm (SD) seems to adjust by shuttling SD components between the SD and the adjacent foot processes (FPs), resulting in changes in SD area that parallel those in perfusion pressure.
Filtrate flow tends to drag podocytes towards the urinary orifice by shear forces, which are highest within the filtration slits. The SD represents an atypical adherens junction, mechanically interconnecting the cytoskeleton of opposing FPs and tending to balance the shear forces.
If under pathological conditions, increased filtrate flows locally overtax the attachment of FPs, the SDs are replaced by occluding junctions that seal the slits and the attachment of podocytes to the GBM is reinforced by FP effacement. Failure of these temporary adaptive mechanisms results in a steady process of podocyte detachment due to uncontrolled filtrate flows through bare areas of the GBM and, subsequently, the labyrinthine subpodocyte spaces, presenting as pseudocysts. In our view, shear stress due to filtrate flow—not capillary hydrostatic pressure—is the major challenge to the attachment of podocytes to the GBM.
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Metadata
Title
Mechanical challenges to the glomerular filtration barrier: adaptations and pathway to sclerosis
Authors
Wilhelm Kriz
Kevin V. Lemley
Publication date
01-03-2017
Publisher
Springer Berlin Heidelberg
Published in
Pediatric Nephrology / Issue 3/2017
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI
https://doi.org/10.1007/s00467-016-3358-9

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