Structural determinants of glomerular hydraulic permeability

Abstract

To elucidate which structures determine the resistance to water movement, we used a computational fluid dynamics approach to determine velocity and pressure fields within the glomerular capillary wall. The model included representations of the endothelial fenestrae, basement membrane, and epithelial filtration slits with slit diaphragms. The input data included dimensions of the various structures from previous electron microscopy studies, as well as the hydraulic permeability recently measured for isolated films of glomerular basement membrane in vitro. The hydraulic resistance of the endothelium was predicted to be small, whereas the basement membrane and filtration slits were each found to contribute roughly one-half of the total hydraulic resistance of the capillary wall. It was calculated that, for a given filtrate flux, the pressure drop within basement membrane in vivo is roughly twice that of "bare" or isolated basement membrane, because of the small fraction of basement membrane area exposed. The dominant resistance in the filtration slit was found to be the slit diaphragm. Predicted values for the overall hydraulic permeability of the capillary wall were within the experimental range derived from micropuncture measurements in normal rats. The model should be a useful tool for analyzing the effects of various structural changes on glomerular hydraulic permeability. This is illustrated by applying the model to recent physiological and morphometric data in nephrotic rats.