Glomerular Permeability

Abstract

Although the structure of renal glomerular capillaries is now well established, little is known about the mechanisms involved in the transfer of substances across their wall from the capillary lumina to the urinary spaces. According to prevailing concepts in renal physiology, the formation of glomerular fluid takes place by passive ultrafiltration of blood plasma through a sieve-like capillary wall provided with rigid pores (1-3). An alternative view assumes that the process involved is one of diffusion across a capillary wall taken to be a gel composed of fibrils of molecular dimensions (4, 5). Neither of these hypotheses, based primarily on permeability studies, takes into account morphological information already available: namely, that the glomerular capillary wall is not composed of a single, homogeneous membrane, but is a multilayered structure.Several suggestions as to the probable glomerular structure which constitutes the filtration barrier have also been proposed as a result of morphological observations: the majority of electron microscopists (e.g., references 6-9) have assumed that the glomerular basement membrane acts as the main filter, because it is the only continuous layer found in the capillary wall. According to another hypothesis (10), the spaces between the foot processes of the visceral epithelial cells act as "slit pores" which allow free passage of water, small molecules, and electrolytes, but restrict the passage of proteins. Up to the present, however, there has been no direct experimental evidence to support either of these assumptions.Our approach to this problem was to attempt to visualize directly the pathways across the glomerular capillary wall by introducing into the blood a par-*

Altered Functional Properties of the Renal Glomerulus in Autologous Immune Complex Nephritis

“…Large membrane-bound vacuoles containing a high concentration of ferritin were present in mesangial and glomerular epithelial cells as well as in the basal portion of the proximal convoluted tubular cells. At these late time periods many ferritin particles were present free within the cytoplasm of these cells, an observation reported by others as well (6). The intracellular distribution of ferritin was essentially similar in control animals but the concentration of ferritin in glomerular and tubular epithelial cell vacuoles appeared to be less.…”

Glomerular Permeability

“…Studies employing ferritin as an electron microscope tracer (4,5) have suggested that the glomerular basement membrane is the normal filtration barrier to this large protein, and that increased basement membrane permeability can account for proteinuria in experimental aminonucleoside nephrosis. In the ferritin studies only small amounts of tracer escaped into the urinary space; thus the mechanism of prorein transfer across the glomerular epithelium was not clarified.…”

Podocytes are key—although albumin never reaches the slit diaphragm

“…[5][6][7] Albumin (as well as other tracer molecules, such as ferritin) is repelled at the level of the endothelium, which argues in favour of a low GSC and-on first look-seemingly supports Comper's hypothesis that the podocyte might not have a role in proteinuria.…”