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Review
. 2009 May;18(3):226-32.
doi: 10.1097/mnh.0b013e3283296044.

Update on the Glomerular Filtration Barrier

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Free PMC article
Review

Update on the Glomerular Filtration Barrier

George Jarad et al. Curr Opin Nephrol Hypertens. .
Free PMC article

Abstract

Purpose of review: The nephrology community lacks a unified view of protein sieving through the glomerular capillary wall. The glomerular capillary wall consists of three distinct but closely interacting layers: the fenestrated endothelium, with its glycocalyx; the podocytes, with their interdigitated foot processes and slit diaphragms; and the intervening glomerular basement membrane. Proteinuria is associated with abnormalities in any one layer, suggesting that each contributes to the glomerular filtration barrier (GFB). Proteinuria can also be induced in the context of a normal glomerular capillary wall. Here, we review some classic studies as well as some newer concepts and present competing hypotheses about the GFB.

Recent findings: Two almost forgotten concepts have recently emerged. One group has challenged the exquisite selectivity of the GFB to albumin and suggested that proteinuria is the result of abnormal tubular uptake. There has also been a reemphasis on diffusion through the glomerular basement membrane as the driving force behind macromolecular filtration. New evidence suggests that the endothelial glycocalyx is an important charge-selective barrier.

Summary: We suggest viewing the GFB as a dynamic rather than as a rigid barrier, requiring three healthy layers and a hemodynamic steady state. Multiple challenges to studying the endothelium, the tubular handling of albumin, and the role of hemodynamic forces will require new tools, new hypotheses, and open minds.

Figures

Figure 1
Figure 1. View of the glomerular capillary wall by freeze fracture deep-etch scanning electron microscopy
The GCW consists of the diaphragm-less fenestrated endothelium (Endo), the GBM with its thick central layer (corresponding to the lamina densa by transmission EM), and podocyte FPs with bridging SDs. Note the thin strands connecting podocytes and endothelial cells to the GBM. Image provided by Dr. John Heuser, Washington University School of Medicine.
Figure 2
Figure 2. GCW charges
Kidneys were perfused with a high concentration of polyethylenimine (PEI) and post-fixed in phosphotungstic acid and osmium. The extent of the endothelial glycocalyx and fenestral plug is clear (large arrows). Note also the podocyte glycocalyx (arrowheads) and GBM charges (small arrows), which are strongest at the laminae rarae internae and externae.

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