Understanding the Glomerular Mesangium through computational modeling

Abstract

The mesangium plays a prominent role in maintaining glomerular homeostasis by contributing to hemodynamic regulation, macromolecule clearance, and immune monitoring. However, it is also intimately involved in the development of glomerular disease. In this work we examine the physics of transport in the mesangial region by creating a computational model. This model suggests that physiological parameters play a key role in controlling the distribution of macromolecules within the mesangium. In particular, it suggests that aberrant glycosylation of IgA in IgA nephropathy may be damaging because of how it changes the Péclet number. The model is then extended to describe transport within the glomerular tuft through the mesangial matrix. Again, we examine this transport under a range of physiological parameters. Our results suggest that transport within the mesangium may operate as one of two broad regimes – an “accumulating” regime where the mesangium provides additional filtration surface area and large macromolecules may accumulate in the region, and a “shunting” regime where the mesangium allows solutes to bypass the full length of glomerular capillary filtration.