Glomerular permselectivity refers to the molecular basis by which the glomerular capillary wall restricts the permeation of macromolecules like proteins based on their size, charge, and configuration. There are two main hypotheses for the selectivity: charge selectivity and size selectivity. While several models have been proposed to explain glomerular filtration, such as the pore model and gel hypothesis, the exact mechanisms remain incompletely understood. Ongoing research aims to further elucidate this complex filtering process.

1. Glomerular Permselectivity

2. Objectives
• Definition of Glomerular permselectivity
• Molecular Basis
• Physiological Significance
• Various Hypothesis

3. Classic Definition
Restriction of permeation of macromolecules
across a glomerular capillary wall on the basis of
molecular size, charge, and physical
configuration.

4. Molecular Basis of Permselectivity

8. Hypothesis for Permselectivity?
• Glomerular Barrier/ Glomerular Filtration
Membrane
1. Charge Selectivity
2. Size Selectivity

9. Charge Selectivity

11. In acquired and chemically induced kidney disease, albuminuria is the result of
dysfunction in proximal tubular cell processing of albumin rather than alterations in
glomerular permeability.

12. • Sieving Coefficient: Albumin concentration in Bowman’s
capsule/albumin concentration in plasma. Describes the
transport of a solute across the GFB in relation to that of a
freely filtered solute.

13. Other Supportive Studies
Chen S, Wassenhove-McCarthy DJ, Yamaguchi Y, et al. Loss of heparan sulfate glycosaminoglycan assembly in podocytes does not
lead to proteinuria. Kidney Int 2008; 74:289–299. (Mice)
Harvey SJ, Jarad G, Cunningham J, et al. Disruption of glomerular basement membrane charge through podocyte-specific
mutation of agrin does not alter glomerular permselectivity. Am J Pathol 2007; 171:139–152.
Van den Born J, Pisa B, Bakker MA, et al. No change in glomerular heparan sulfate structure in early human and experimental
diabetic nephropathy. J Biol Chem 2006; 281:29606–29613.
Van den Hoven MJ, Wijnhoven TJ, Li JP, et al. Reduction of anionic sites in the glomerular basement membrane by heparanase
does not lead to proteinuria. Kidney Int 2008; 73:278–287. (Mice)
Goldberg S, Harvey SJ, Cunningham J, et al. Glomerular filtration is normal in the absence of both agrin and perlecan-heparan
sulfate from the glomerular basement membrane. Nephrol Dial Transplant 2009. (Mice)

21. Size Selectivity

23. The Albumin Retrieval Hypothesis

24. Figure 1: The Filtering Glomerulus

25. Limitations
Why the filter does not clog?

26. The Electrokinetic Model
• Electrical field (filtration dependent potential
or streaming potential) across the GFB
(Electrically conductive)

28. The Pore Model (Two Pore
Model/Heteroporous Model)

30. The Gel Hypothesis

32. The Gel Permeation Hypothesis

35. Key Points
• The functioning of the glomerular filter is still not
completely understood
• The glomerular filter is an excellent model system for
filtering capillaries
• Several models for glomerular filtration have been
proposed and have made major contributions to our
understanding of glomerular filtration
• A large body of experimental data has been published
that is compatible with the notion of a notable
streaming potential across the GFB, but more studies
are needed

36. Thank you!
• Dr. Somers

37. References
• As included