The Endothelium in Diabetic Nephropathy
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Diabetes is characterised by widespread endothelial cell dysfunction that underlies the development of both the micro- and macrovascular complications of the disease, including nephropathy, cardiomyopathy, and non-proliferative retinopathy. In the kidney, major changes are noted in glomerular endothelial cell structure in their fenestrations and glycocalyx. These changes, along with endothelial cell loss and capillary rarefaction in both the glomerulus and tubulointerstitium, lead to the progressive loss of glomerular filtration that render diabetes the most common cause of end-stage renal disease in much of the developed world. New treatments in diabetes that directly address the abnormal structure and function of the endothelial cell are desperately needed.
KeywordsEndothelial Diabetes Glycocalyx Proteoglycans Fenestrae Glomerular filtration Fibrosis Ischaemia Hypoperfusion Capillary rarefaction Endothelial-mesenchymal transition Vascular endothelial growth factor Transforming growth factor-ß
The author regrets that, owing to space constraints, much of the excellent work of many researchers in the area has not been included in this review. The author acknowledges the generous support of grants from the Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, and the Kidney Foundation of Canada. Dr. Gilbert is the Canada Research Chair in Diabetes Complications, and support for this work is thanks in part to the Canada Research Chair Program.
Compliance with Ethics Guidelines
Conflict of Interest
Richard E. Gilbert is a founder and shareholder in Fibrotech Therapeutics Pty Ltd., and has received consulting fees from Mesoblast Ltd. and honoraria for lectures and research grants from Astra-Zeneca, Bristol-Myers Squibb, and Merck.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
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