Abstract
Although abnormalities in the glomerular epithelial cell, the podocyte, have been
appreciated for some time, it is only recently that their significance and the underlying
mechanisms for the changes have begun to be explored. There is a decrease in podocyte
number early in diabetes, with further decreases as albuminuria increases. The number
of podocytes is inversely related to the degree of albuminuria in both cross-sectional
and longitudinal studies. Foot process width is increased in proteinuria, the width
correlating with albuminuria. Loss of nephrin - both mRNA and protein - occurs some
time after the onset of diabetes and is also inversely related to proteinuria. The
amount of the α3β1 integrin on the basement-membrane surface of the foot process of the podocyte is
also reduced in diabetes. Loss of nephrin and α3β1 integrin is induced by both hyperglycaemia and mechanical stretch. Agents that inhibit
the renin-angiotensin system, but not other agents that reduce proteinuria, restore
nephrin expression and prevent the structural changes seen in the podocyte in diabetes.
Thus, changes in the podocyte contribute to the proteinuria of diabetic nephropathy
and can be ameliorated by inhibition of the renin-angiotensin system.
Key words
Diabetic glomerulosclerosis - Proteinuria - Glomerular filtration barrier - Podocyte
foot process - Nephrin - Slit diaphragm
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Prof. Sally M. Marshall
Diabetes Research Group · School of Clinical Medical Sciences · 4th Floor · Leech
Building
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Fax: + 44(191)2220723
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