The proposed research is aimed at the development of accurate and predictive theories for two elements of renal function. The first of these concerns the mechanisms whereby glomerular capillaries selectively restrict the filtration of certain macromolecules. Proteinuria resulting from a disruption of this filtration barrier is a hallmark of kidney disease, and a better understanding of normal and altered glomerular selectivity promises to provide insight into the underlying disease mechanisms, as well as to offer new methods for monitoring the progress of patients. Theoretical models will be developed or extended to describe movement of macromolecules of varying size, charge and molecular configuration through porous membranes. The membranes will be represented either as an array or cylindrical pores or as a network of fibers. In vitro experiments will be used to examine elements of these theories and to characterize test macromolecules. The theories will be used to interpret measurements of glomerular selectivity in studies of experimental renal disease in rats, and in various human glomerulopathies. Adjustments in the rate at which filtered bicarbonate is reabsorbed by the kidney provide one of the body's major defenses against disruptions of acid-base balance. Recent measurements of carbon dioxide partial pressure (PCO2) in the rat kidney have raised a number of important questions concerning the intrarenal handling of carbon dioxide and bicarbonate, which provide a second focus for the proposed research. Theoretical models will be developed to rationalize observed differences in PCO2 between peritubular capillary and arterial blood, and among tubules and microvessels on the surface of the renal cortex. These models will involve detailed consideration of mass transfer, chemical kinetics, and chemical equilibria in blood vessels and renal tubules. Comparison of the theoretical predictions with experimental results in the rat should provide a sensitive test of current hypotheses concerning bicarbonate reabsorption. The proposed research will involve collaboration among chemical engineers, renal physiologists and clinical nephrologists.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Method to Extend Research in Time (MERIT) Award (R37)
Project #
Application #
Study Section
General Medicine B Study Section (GMB)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Massachusetts Institute of Technology
Schools of Engineering
United States
Zip Code
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

Showing the most recent 10 out of 35 publications