Summary
The long-term complications of diabetes are characterized by pathologic changes in
both the microvasculature and conduit vessels. Although the fenestrated glomerular
endothelium classically has been viewed as providing little in the way of an impediment
to macromolecular flow, increasing evidence illustrates that this is not the case.
Rather, hyperglycemia-mediated endothelial injury may predispose to albuminuria in
diabetes both through direct effects and through bidirectional communication with
neighboring podocytes. Although neo-angiogenesis of the glomerular capillaries may
be a feature of early diabetes, particularly in the experimental setting, loss of
capillaries in the glomerulus and in the interstitium are key events that each correlate
closely with declining glomerular filtration rate in patients with diabetic nephropathy.
The hypoxic milieu that follows the microvascular rarefaction provides a potent stimulus
for fibrogenesis, leading to the glomerulosclerosis and tubulointerstitial fibrosis
that characterize advanced diabetic kidney disease. Given the pivotal role the endothelium
plays in both the development and the progression of diabetic nephropathy we need
effective strategies that prevent its loss or accelerate its regeneration. Such advances
likely will lead not only to improved tissue oxygenation and reduced fibrosis, but
also to improved long-term renal function.
Keywords
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Article info
Footnotes
Financial support: Supported in part by grants from the Canadian Institutes of Health Research and from the Physicians' Services Incorporated Foundation; Andrew Advani is a Canadian Diabetes Association Clinician Scientist; and Richard Gilbert is a Canada Research Chair in Diabetes Complications.
Conflict of interest statement: none.
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© 2012 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
