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Glomerular permeability to macromolecules in the Necturus kidney
George A Tanner1, Catarina Rippe, Youzhi Shao
1Department of Cellular and Integrative Physiology, Indiana Univ. School of Medicine, 635 Barnhill Dr., MS 332, Indianapolis, IN 46202, USA. gtanner@iupui.edu
American Journal of Physiology. Renal Physiology
|April 3, 2009
Summary
The glomerular basement membrane does not filter macromolecules by size or charge. The podocyte slit diaphragm acts as the primary filtration barrier, preventing albumin from passing and mesangial cells clear penetrated molecules to prevent filter clogging.
Area of Science:
- Nephrology
- Physiology
- Cell Biology
Background:
- The precise mechanisms of glomerular filtration, including the primary filtration barrier, charge effects, and clog prevention, remain debated.
- Understanding these processes is crucial for diagnosing and treating kidney diseases.
Purpose of the Study:
- To investigate the glomerular filtration barrier's role in macromolecule filtration.
- To determine the impact of molecular size and electrical charge on filtration.
- To identify the main barrier to albumin filtration and the mechanism preventing filter clogging.
Main Methods:
- Utilized a two-photon microscope for in vivo visualization of fluorescently labeled probes in Necturus maculosus glomeruli.
- Measured glomerular basement membrane (GBM)/plasma concentration ratios for various macromolecules (e.g., myoglobin, ovalbumin, albumin, dextrans) and inulin.
- Examined glomerular sieving coefficients (GSCs) for native and neutral macromolecules to assess charge effects.
Main Results:
- The GBM did not discriminate between inulin and smaller macromolecules like myoglobin, ovalbumin, and serum albumin.
- Larger dextrans (500 and 2,000 kDa) showed significantly lower GBM/plasma concentration ratios than inulin.
- GSCs decreased with increasing molecular mass, and serum albumin had very low GSCs, indicating the podocyte slit diaphragm is the main barrier to albumin.
- Electrical charge had no detectable effect on the filterability of human serum albumin or 40 kDa dextran.
- Mesangial and endothelial cells were observed to take up macromolecules that penetrated the GBM, suggesting a role in preventing filter clogging.
Conclusions:
- The glomerular basement membrane (GBM) does not act as a size or charge-selective barrier for most macromolecules.
- The podocyte slit diaphragm is identified as the primary filtration barrier preventing albumin passage.
- Mesangial and endothelial cells play a role in clearing macromolecules from the GBM, preventing filter clogging.
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