Modeling combined transport of water and test macromolecules across the glomerular capillary barrier: dynamics of the permselectivity.

Abstract

The structure, function, and composition of the basement membrane of the glomerular capillaries of the mammalian kidney have been extensively studied, in light of the membrane's important physiological role in glomerular filtration of macromolecules and of its frequent involvement in renal diseases. An analytical mathematical model, based on the fiber matrix theory, was developed to describe the dynamics of the permselective function of the glomerular capillary barrier using mainly its hemodynamic and morphometric variables. The glomerular basement membrane was represented as a homogeneous three-dimensional meshwork of fibers of uniform length (L(f)), radius (R(f)), and packing density (N(fv)) and characterized by a local Darcy permeability (a measure of the intrinsic hydraulic conductance of the glomerular basement membrane). The model was appropriate for simulating in vivo fractional clearance data of neutral test macromolecules from an experimental rat model. We believe that the L(f) and R(f) best-fit numerical values, characterizing a glomerular basement membrane geometrical arrangement, may represent diagnostic measures for renal function in health and disease. That is, these parameters may signify new insights for the diagnosis of some human nephropathies and possibly may explain the beneficial effects and/or sites of action of some pharmacological modifiers (e.g., angiotensin converting enzyme inhibitors).