Glomerular Permselectivity

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Glomerular Permselectivity

Transcript of Glomerular Permselectivity

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Glomerular Permselectivity

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Objectives

• Definition of Glomerular permselectivity• Molecular Basis• Physiological Significance• Various Hypothesis

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Classic Definition

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

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Molecular Basis of Permselectivity

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Hypothesis for Permselectivity?

• Glomerular Barrier/ Glomerular Filtration Membrane

1. Charge Selectivity2. Size Selectivity

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Charge Selectivity

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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.

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• 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.

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Other Supportive StudiesChen 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)

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Size Selectivity

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The Albumin Retrieval Hypothesis

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Figure 1: The Filtering Glomerulus

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Limitations

Why the filter does not clog?

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The Electrokinetic Model

• Electrical field (filtration dependent potential or streaming potential) across the GFB (Electrically conductive)

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The Pore Model (Two Pore Model/Heteroporous Model)

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The Gel Hypothesis

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The Gel Permeation Hypothesis

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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

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Thank you!

• Dr. Somers

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References

• As included

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