Novel Anatomic and Macromolecular Models Define Realistic Glomerular Barrier
- Glomerular Diseases: Podocyte Biology - II
November 04, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1403 Podocyte Biology
- Luke, Robert L., Maine Medical Center, Portland, Maine, United States
The glomerular barrier has been studied extensively using the polysaccharides dextran and Ficol, both modeled as rigid impervious spherical particles. Recent glomerular reconstructions reveal that afferent and efferent glomerular arterioles are joined by non-communicating branches; these parallel tubes are combined into a single uniform cylindrical filter composed of the two most restrictive layers of the glomerular capilary wall, basement membrane and visceral epithelial cells joined by slit diaphragm.
The classic matrix formulation is modified for flow dependent solute size because water penetrates partial draining polysaccharides such as dextran, but not non-draining proteins; linear regression yields fiber density from slope and transepithelial shunt from intercept. This model is introduced with the permeability of α1acidglycoprotein, albumin, transferrin, IgG, and α2macroglobulin in newly reported patients with primary glomerular disease and completed using appropriate hydrostatic pressures, vascular dimensions, and the permeability of dextran, Ficoll, albumin, and IgG in similar patients obtained from the literature.
Fiber density was similar to fiber density reported for islolated basement membrane and was essentially the same in controls and patients; epithelial shunts were proportional to total urinary protein excreted, fiber density was not. Effective polysaccharide size decreased when confined by fibers in basement membrane and when confined by streamlines in slit pore. Four-fold higher fiber density encountered by small polysaccharides compared to proteins and large polysaccharides reflect the stratified nature of the glomerular basement membrane and define two pathways through the glomerular capillary wall, a selective route direct through lamina densa and slit diaphragm, a non-selective indirect route through more lamina rara externa and infrequent widely spaced epithelial defects. Filtration area was similar to reported anatomic measurements in controls and was decreased in proportion to histologic abnormality in patients.
Dextran and Ficoll are more permeable than similar size proteins such as albumin and IgG because moving water penetrates, rearranges, and aligns chemically similar polysaccharides. In disease the basement membrane is preserved, but the visceral epithelium is not.