Altered glomerular permeability as a result of focal detachment of the visceral epithelium

Altered glomerular permeability as a result of focal detachment of the visceral epithelium. Changes in the permeability of the glomerular capillary wall (GCW) to native ferritin (NF), following detachment of the visceral epithelium from the glomerular basement membrane (GBM) were investigated. Detachment was induced by either perfusing kidneys with highly purified neuraminidase or by the induction of nephrosis through administration of puromycin aminonucleoside (PAN). Both experimental treatments resulted in marked glomerular ultrastructural changes which were characterized by focal detachment of the visceral epithelium from the GBM, replacement of the normal pattern of interdigitating foot processes with flattened expanses of continuous epithelium at certain areas of the GCW, and a generalized loss of the sialic acid-rich epithelial cell coat in areas where the epithelium was detached as well as where it remained adherent. These changes were more frequent and prominent in the paramesangial regions of the glomeruli. When experimentally treated kidneys were perfused with NF, the tracer leaked into the urinary spaces in those areas of the GBM where the epithelium was detached. By contrast, in those areas of the GCW where the epithelium remained adherent, the tracer localized within the GBM mainly at the level of the lamina rara interna (LRI), and none of it appeared in the urinary spaces. Nephrotic and neuraminidase control kidneys were ultrastructurally normal, NF localizing mainly in the inner layers of the GBM. These data are consistent with the idea that the firm attachment of the epithelial foot processes to the GBM plays a vital role in determining the permselectivity properties of the GCW to plasma macromolecules. Alteration de la permeabilite glomerulaire par detachement focal de lepithelium visceral. Les modifications de la permeabilite de la paroi du capillaire glomerulaire (PCG) a la ferritine native (FN) apres detachement de lepithelium visceral de la membrane basale glomerulaire (MBG) etaient etudie. Le detachement a ete induit soit en perfusant les reins avec de la neuraminidase hautement purifiee, soit en induisant une nephrose par administration de puromycine aminonucleoside (PAN). Les deux protocoles experimentaux ont entraine des modifications marquees de l'ultrastructure glomerulaire caracterisees par un detachement de lepithelium visceral de la MBG, par le remplacement de l'aspect normal d'intrication des pieds des podocytes par des prolongements aplatis d'epithelium continu a certains endroits de la PCG, et par une perte generalisee de la couverture cellulaire epitheliale riche en acide sialique dans les zones ou lepithelium s'est detache comme dans celles ou il est reste adherent. Ces modifications etaient plus frequentes et plus marquees dans les regions paramesangiales des glomerules. Quand des reins ainsi traites etaient perfuses avec de la FN, le traceur fuyait dans les espaces urinaires des zones ou l'epithelium de la MBG s'etait detache. En revanche, dans les zones de PCG ou Tepithelium demeurait adherent, le traceur restait localise principalement dans la lamina rara interna (LRI) de la MBG, et il n'en apparaissait pas dans les espaces urinaires. Les reins controles etaient d'ultrastructure normale, la FN restant principalement localisee au niveau des couches internes de la MBG. Ces donnees sont en accord avec l'idee que la solidite d'attachement des pedicelles epitheliaux a la MBG joue un role vital dans les proprietes de permselectivite de la PCG aux macromolecules plasmatiques.