Glomerular filtration barrier structure and its alterations. Second part

Abstract

The main objective of this second part of the "Glomerular Filtration Barrier (GFB)" review is to highlight sorne concepts previously defined in the first part of this issue and to analyze current concepts regarding the pathophysiology of sorne glomerular diseases derived from alterations in this barrier.
Although the podocyte always dominated the focus of our attention, recent evidence derived from ontogenic analysis of the endothelial barrier encouraged us to build up an integrated vision of the GFB. It is widely recognized that the endothelial layer has unique features like those related to structural and functional characteristics -like the presence of fenestrae and diaphragm- that are distinctive.
Two endothelial-derived growth factors (angiotoietin 1 and 2) have antagonistic functions and are believed to have a role in some glomerular diseases.
We have already mentioned that some regulatory proteins, such as cyclines and proteases, are able to react to different stimuli by retaining the integrity of the GFB or otherwise inducing glomerular injury. Podocytes and endotelial ceIls also express components of the renin-angiotensin-system; whose effects on the GFB are incompletely recognized.
The renal involvement in diabetes mellitus was considered until recently as a primary mesangial condition with the effacement of the foot processes as a consequence of the increased urine protein excretion. Nonetheless it has been amply recognized the involvement of the podocyteborne protein, nephrine.
C5b-9-complemcnt associated podocyte activation has been considered as responsible for the development of membranous nephropathy.
Similarly, steroid-resistant nephrotic syndrome, in children was associated with autosomic recessive genes mutations encoding different proteins with deficit of nephrin, podocyn, laminin B-2, phospholipase C-e.; and in adult patients alteration of ACTN4 as well as in the TRPC6 calcium channel, expressed as focal and segmental glormerulosclerosis (FSGS).
The role of esteroids, statins and the retinoic acid (the latter for HlV-related nephropathy) have also been extensively considered, as well as the 1,25 D3 vitamins.