FIGURE 2 —

A. Schematic of the pore model formula to calculate the albumin sieving coefficient (i.e. the fraction that passes the glomerular filter). Two fluxes are added: convection and diffusion. In order to match experimental data, correction factors were introduced (“hindrance factors”) that modify the result by several orders of magnitude. B. Anti-clogging mechanism of the electrokinetic model. If a macromolecule (XX) is trapped within the filter, the electrokinetic model predicts that it will be removed by electrophoresis since macromolecules are virtually always electrically charged. A small fraction of macromolecules may not bear sufficient charges, and it is predicted they will be removed by endocytosis by endothelial cells and podocytes. C. Summary of permeability experiments using wild-type negatively charged (pI = 4.6) or neutralized/slightly positively charged ferritin (pI = 8.5). Negative ferritin is excluded from the filter, while neutral ferritin passes the filter and is partially retained by the GBM, clogging the filter. The electrokinetic model provides a consistent explanation for all of the experimental findings, since negative ferritin is repelled while neutral ferritin freely enters, passes, and clogs the filter. The pore model cannot explain why negative ferritin does not enter the filter. Regarding neutralized ferritin, the pore model predicts correctly that neutral ferritin passes the filter better (because the apparent pore diameter appears wider) but it predicts less retention and clogging, which is inconsistent with experimental results. Hc = convective hindrance factor; Hb = diffusive hindrance factor; pI = isoelectric point.