Structure and Properties of the Glomerular Filtration Barrier in Vertebrates: Role of a Charge in Protein Filtration

The renal glomerulus is a unique structure that distinguishes the nephrons of vertebrates from the nephridia of invertebrate animals, providing a direct link between the circulatory and excretory systems and the most effective control of the composition of the internal environment due to significant intensification of filtration. Here, we address the modern ideas on the structure of the glomerular filtration barrier (GFB) in representatives of all major vertebrate taxa (cyclostomes, fish, amphibians, reptiles and birds, mammals) with a focus on the significance of the charge of GFB components for its selectivity. We also describe the approaches to probing the contribution of anionic glomerular components to preventing the loss of plasma proteins, and consider the main functional models of the glomerular filter available in the literature. We demonstrate that the negative charge is a distinctive feature of the glomerular filter in all vertebrates. A multiple increase in the glomerular filtration rate (from lower vertebrates to birds and mammals) was accompanied by a number of structural alterations that ensured the passage of a significant volume of water and low molecular weight solutes through the GFB, e.g., an increase in the number and ordering of glomerular capillary endothelial fenestrae, thinning of the glomerular basement membrane, and total exclusion of cellular elements from its composition. A comparative physiological analysis of the data on the GFB in diverse vertebrate taxa provides a strong validation of the electrokinetic glomerular filtration model, as it explains most convincingly the importance of the evolutionarily conserved structure of podocytes and the role of overall fixed negative charges in the filter wall for preventing the loss of macromolecules (primarily proteins) from blood at different ultrafiltration intensities.