Mesangial Region Recovers More Protein than Podocyte Layer Leaks

Background: During filtration the glomerular barrier leaves most protein behind in the blood, but the amount of protein that crosses basement membrane in health and disease likely exceeds tubular absorption capacity. Methods: Molecular and anatomic models are introduced with the permeability of a1acidglycoprotein, albumin, transferrin, IgG, a2macroglobulin, and IgM in 44 new patients with glomerulonephritis and completed using histologic measurements and the permeability of dextran, Ficoll, albumin, and IgG in 15 similar case groups obtained from the literature. The classic fiber formulation is modified for flow dependent size of poly-sucrose dextran and Ficoll, but not for the size of proteins, because water interacts with chemically similar sucrose, but water separates from chemically dissimilar amino and carbonyl groups. Linear regression yields partial draining depth, fiber concentration, and trans-podocyte shunt. Glomerulus is divided into non-filtering mesangial and filtering capillary regions, porosity determined by the classic matrix formulation. Results: Collision radii of 30-40Å dextran and Ficoll are decreased by partial draining depth 8-12Å, a shell of width similar to 7-9Å shielding length, an independently determined property of partial draining solutes; fiber concentrations of 0.15 in controls and 0.12 in patients represent lamina densa and correspond with albumin filtration fractions of 0.009 and 0.017, leakage of 62 and 31 grams per day, respectfully. In patients, proteins, 54-60Å dextran, and 60-68Å Ficoll reveal fiber concentration 0.03 that represents lamina rara externa. Neither fiber concentration correlated with urinary protein excretion (UPX). Trans-podocyte shunts increased from 0.000009 in controls to 0.011 in patients and correlated with UPX (n=15, r=0.9492, p<0.001). Mesangial volume increased from 0.47X106mm3 in controls to 1.75 X106mm3 in patients and correlated with UPX (n=15, r=0.5880, 0.01>p>0.001). Conclusion: Podocyte layer leaks some protein, more in disease, but mesangial channels recover more protein unless compromised by increased cells, matrix, or aggregated proteins such as immune complexes, aberrant IgA, or amyloid. Recovery path begins in lamina rara externa and continues back across basement membrane supported by mesangium that is more porous during filtration reversal than basement membrane compressed between endothelium and podocytes.