Transport of macromolecules in glomerular filtration

Abstract

The main function of kidneys is to retain the normal blood composition and volume through blood filtration: the first step of which occurs at the glomerular capillary wall that consists of three layers: the endothelium cell layer, the glomerular basement membrane (GBM) and the epithelial foot processes with their interconnecting slit diaphragm. Our research focuses on the transport of myoglobin, a biomarker for muscle damage and one of the causes of acute renal failure. A hydrodynamic model is introduced to describe hindered transport of electrically-neutral macromolecules through the epithelial slit and a glomerular basement membrane (GBM). The slit diaphragm is modeled as a row of parallel cylindrical fibers and the GBM is treated as an isotropic fibrous medium. Numerically calculated sieving coefficient of myoglobin, a product of the sieving coefficient of the slit diaphragm and that of the GBM, is found to be in good agreement with sieving coefficient obtained from counting radioactivity of radiolabeled myoglobins in blood and urine, if, in the calculation, GBM fiber radii are assumed to be 0.5 nm (with the presence of type IV collagen in the GBM neglected). With the gap between adjacent fibers in the epithelial slit diaphragm (L) assumed to be about 10 nm, the absence of the slit diaphragm increases the sieving coefficient by only 6-7%. It seems that the GBM contributes significantly to the restriction of myoglobin in glomerular filtration, although it might still be too early to say that the contribution of slit diaphragm is negligible, given that the values of L = 10 nm is the upper limit. Further investigation is needed to fully understand the contribution of each layer.