Novel Molecular and Glomerular Models Expand Pore Theory

Objective is to show glomerulus is filtering capillary and protein recovering mesangium, in contrast with pore theory that replaces entire glomerulus with a conceptual membrane and requires tubule recover all leaked protein. Hypothesis is supported by modeling molecular probes dextran and Ficoll partial draining solutes, their behavior in moving water, because these two sucrose polymers interact with and extend the tetrahedral structure of water, unlike pore theory that considers them impervious Stokes-Einstein spheres, their behavior in stationary water. Herein defined partial draining depth decreases dextran and Ficoll size, but not protein size in the classic fiber formulation; linear regression yields trans-epithelial shunt from intercept and fiber density from slope. Glomerular model divides volume into non-filtering region covered by basement membrane bordered by mesangium and epithelium and filtering region covered by basement membrane bordered by capillary lumen and epithelium where porosity is defined by the classic matrix formulation. Anatomic and molecular models introduced with the permeability of a 1 acidglycoprotein, albumin, transferrin, IgG, a 2 macroglobulin, and IgM in newly reported patients with primary glomerular disease are completed using histologic measurements and the permeability of dextran, Ficoll, albumin, and IgG in similar cases obtained from the literature. Log clearance of 30Å-40Å dextran and Ficoll extrapolates to unity because average fluid shear, 7400 sec -1 in slit pore, molds and aligns them with slit diaphragm apertures. Urinary excretion of protein (UXP) correlated with shunts, 0.000009 in controls and 0.011 in patients (n=15, r=0.9492, p<0.001). Partial draining depth 10.2Å, similar to 11.8Å independent determined shielding length, indicated effective dextran and Ficoll size decreased 29% when confined in basement membrane. Fiber density, 0.15 in controls and average 0.12 in patients, did not correlate with UXP; associated albumin filtration fractions 0.009 and 0.017 corresponded with leakage of 62 and 31 grams/day. Capillary volume, 0.92 in controls and 0.72X10 6 mm 3 in patients, did not correlate with UXP. Mesangial volume, 0.47 in controls and 1.75X10 6 mm 3 in patients, correlated with UXP (n=15, r=0.5880, 0.01>p>0.001). Log clearance of proteins, 60Å-68Å Ficoll, and 56Å-60Ådextran yielded 0.03 lamina rara externa fiber density. In conclusion, basement membrane blocks most albumin and is essentially unchanged in disease. Epithelium leaks some albumin, more in disease, but mesangial channels recover more unless pathway is compromised by increased matrix, selective as reported in diabetic patients, or combined with blockage by aggregated proteins such as immune complexes, aberrant IgA, or amyloid. Retrieval path begins in lamina rara externa and continues through basement membrane supported by mesangium that is much more porous than basement membrane compressed against epithelium. Novel molecular and glomerular models indicate therapy must rehabilitate podocytes and mesangium in addition to suppressing abnormal immune system. American Heart Association This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.