The normal glomerular capillary wall is extremely permeable to water, and yet very effective at preventing the loss of plasma proteins into the glomerular ultrafiltrate. In the principal forms of kidney disease both of these aspects of glomerular function tend to be impaired: there is a reduced capacity for filtration of water, accompanied by less ability to selectively retain large molecules in plasma. The structural basis for normal or impaired glomerular permeability properties remains poorly understood. The overall objective of the proposed research is to develop theoretical models which will relate these functional properties to the physical characteristics of the structures that comprise the capillary wall, which include the fenestrated endothelium, glomerular basement membrane (GBM), and epithelial filtration slits with slit diaphragms.
One specific aim i s to characterize the movement of water and macromolecules across novel agarose-dextran gels that are designed as experimental models for the GBM.
A second aim, also related to transport across the GBM, is to develop a theory to predict the effects of abundant solutes (such as the major plasma proteins) on the movement of tracers of varying size through gels or fibrous membranes. The results from these studies of GBM-like materials, together with improved hydrodynamic descriptions of macromolecule movement across the cellular parts of the barrier, lead to a third objective, which is to more accurately simulate filtration of water and uncharged macromolecules in the glomerulus as a whole. Additional aims are to apply the structure-based hydrodynamic models in collaborative studies of human glomerulopathies, and to extend them to describe intraglomerular signalling events that involve the movement of macromolecules between the glomerular epithelium and endothelium.
| Lazzara, Matthew J; Deen, William M (2007) Model of albumin reabsorption in the proximal tubule. Am J Physiol Renal Physiol 292:F430-9 |
| Kosto, Kimberly B; Deen, William M (2005) Hindered convection of macromolecules in hydrogels. Biophys J 88:277-86 |
| Lazzara, Matthew J; Deen, William M (2004) Effects of concentration on the partitioning of macromolecule mixtures in agarose gels. J Colloid Interface Sci 272:288-97 |
| Deen, William M; Lazzara, Matthew J (2004) Glomerular filtration of albumin: how small is the sieving coefficient? Kidney Int Suppl :S63-4 |
| Kosto, Kimberly B; Panuganti, Swapna; Deen, William M (2004) Equilibrium partitioning of Ficoll in composite hydrogels. J Colloid Interface Sci 277:404-9 |
| Hoang, Khoi; Tan, Jane C; Derby, Geraldine et al. (2003) Determinants of glomerular hypofiltration in aging humans. Kidney Int 64:1417-24 |
| White, Jeffrey A; Deen, William M (2002) Agarose-dextran gels as synthetic analogs of glomerular basement membrane: water permeability. Biophys J 82:2081-9 |
| Lazzara, M J; Deen, W M (2001) Effects of plasma proteins on sieving of tracer macromolecules in glomerular basement membrane. Am J Physiol Renal Physiol 281:F860-8 |
| Deen, W M; Lazzara, M J; Myers, B D (2001) Structural determinants of glomerular permeability. Am J Physiol Renal Physiol 281:F579-96 |
| Edwards, A; Daniels, B S; Deen, W M (1999) Ultrastructural model for size selectivity in glomerular filtration. Am J Physiol 276:F892-902 |
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