Mechanical challenges to the glomerular filtration barrier

• Verfasst von: Kriz, Wilhelm [VerfasserIn]
• Verfasst von: Lemley, Kevin V. [VerfasserIn]
• Titel: Mechanical challenges to the glomerular filtration barrier
• Titelzusatz: adaptations and pathway to sclerosis
• Verf.angabe: Wilhelm Kriz, Kevin V. Lemley
• Jahr: 2017
• Jahr des Originals: 2016
• Umfang: 13 S.
• Fussnoten: First published: 23 March 2016 ; Gesehen am 28.06.2018
• Titel Quelle: Enthalten in: Pediatric nephrology
• Ort Quelle: Berlin : Springer, 1987
• Jahr Quelle: 2017
• Band/Heft Quelle: 32(2017), 3, Seite 405-417
• ISSN Quelle: 1432-198X
• DOI: doi:10.1007/s00467-016-3358-9
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 157700180X

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.