The glomerular basement membrane: not gone, just forgotten
Marilyn G. Farquhar
Marilyn G. Farquhar
Published August 1, 2006
Citation Information: J Clin Invest. 2006;116(8):2090-2093. https://doi.org/10.1172/JCI29488.
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Commentary

The glomerular basement membrane: not gone, just forgotten

Abstract

The glomerular capillaries function as the filtration barrier that retains albumin and other plasma proteins in the circulation. The unresolved question that has been asked for more than 50 years is, Which structural component of these capillaries constitutes the main molecular sieve that normally retains albumin and allows its passage in diseases associated with proteinuria? There is considerable evidence implicating both the glomerular basement membrane (GBM) and the epithelial filtration slits as the barrier. However, the prevailing point of view at present is that the slit diaphragms bridging the filtration slits are responsible for this important function, and evidence implicating the GBM is largely ignored or forgotten. In this issue of the JCI, Jarad et al. show that in laminin β2–deficient (Lamb2–/–) mice, proteinuria can be directly attributed to the altered composition of the GBM (see the related article beginning on page 2272). Changes in the permeability of the GBM and its organization were primary to changes in the epithelium, as they preceded foot process effacement and loss of slit diaphragms.

Authors

Marilyn G. Farquhar

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Figure 1

Diagram of the glomerulus in normal andLamb2–/– mice.

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Diagram of the glomerulus in normal andLamb2–/– ...
(A) In the normal glomerulus, the anionic sites are concentrated in the lamina rara interna (LRI) and lamina rara externa (LRE) of the GBM and distributed at regularly spaced intervals. Also shown is the pathway of the glomerular filtrate (arrows). The filtrate passes through the endothelial fenestrae, permeates the GBM, and passes through the filtration slits to reach the urinary spaces. LD, lamina densa. (B) In the nephrotic Lamb2–/– mice, the disorganization of the GBM occurs as the distribution of the anionic sites is irregular and extends beyond the lamina densa. As a result, increased amounts of ferritin and albumin pass through the GBM. Importantly, albuminuria was detectable shortly after birth and preceded podocyte foot process effacement, the latter of which was observed approximately 2 weeks after birth.