Title:Glomerular Endothelium and its Impact on Glomerular Filtration Barrier in Diabetes: Are the Gaps Still Illusive?
Volume: 25
Issue: 13
Author(s): Joseph Fomusi Ndisang*
Affiliation:
- Department of Physiology, University of Saskatchewan College of Medicine, 107 Wiggins Road, Saskatoon, SK, S7N 5E5,Canada
Keywords:
Glomerular filtration barrier, endothelium, diabetes, podocytes, glomerular basement membrane, kidney
dysfunction.
Abstract: Background: Glomerular capillaries are lined with highly specialized fenestrated
endothelium which are primarily responsible to regulate high flux filtration of fluid
and small solutes. During filtration, plasma passes through the fenestrated endothelium
and basement membrane before it reaches the slit diaphragm, a specialized type of intercellular
junction that connects neighbouring podocytes.
Methods: A PubMed search was done for recent articles on components of the glomerular
filtration barrier such as glomerular endothelial cells, podocytes and glomerular basement
membrane, and the effect of diabetes on these structures.
Results and Conclusion: Generally, the onset of kidney dysfunction in many diabetic patients
is characterized by albuminuria/proteinuria, a pathophysiological event triggered by
several factors including; (i) endothelial activation and shading of glycocalyx, (ii) loss of
endothelial cell function, (ii) re-uptake of albumin by podocyte through a scavenger receptors
and (iv) rearrangement of podocyte cytoskeleton. Howeover, as podocyte effacement
does not always lead to proteinuria, the dynamic interplay between all constituents
of the glomerular filtration barrier including podocytes, endothelial cells and the basement
membrane may be fundamental for the effective filtration in healthy individuals. Thus, a
putative cross-talk amongst podocytes, endothelial cells and the basement membrane in
the homeostasis of glomerular function is envisaged. Although, the exact nature of this
cross-talk remains to be clearly elucidated, it is possible that the interaction between: (i)
glomerular endothelial cells and podocytes, (ii) glomerular endothelial cells and glomerular
basement membrane, (iii) podocytes and glomerular basement membrane, and (iv) the
simultaneous interaction amongst the three components collectively underpin effective
filtration in healthy individuals. A comprehensive understanding of these different interactions
still remains elusive. The elucidation of these multifaceted interactions will set the
stage for greater understanding of the pathophysiology of kidney dysfunction.