Structural-functional relationships in diabetic nephropathy.

Abstract

A s bstract. Renal biopsies in 45 patients with insulin-dependent diabetes mellitus (IDDM) were examined by semiquantitative light microscopy and quantitative electron microscopic stereologic morphometry. In these 14 males and 31 females, aged 13-52 yr, who had had IDDM for 2.5-29 yr there was no strong relationship between either glomerular basement membrane (GBM) thickness or mesangial expansion and duration of IDDM. There was only a weak relationship between the thickness of the GBM and expansion of the mesangium. Thus, GBM thickening and mesangial expansion in IDDM occur at rates that often differ from one another and that vary greatly among patients. The clinical manifestations of diabetic nephropathy, albuminuria, hypertension, and decreased glomerular filtration rate related poorly or not at all to GBM thickening. In contrast, all light and electron microscopic measures of mesangial expansion were strongly related to the clinical manifestations of diabetic nephropathy, although in the absence of these clinical findings, it was not possible to predict the severity of any of the diabetic glomerular lesions. Mesangial expansion had strong inverse correlations with capillary filtering surface area density. It is hypothesized that mesangial expansion could lead to glomerular functional deterioration in IDDM by restricting the glomerular capillary vasculature and its filtering surface. However, capillary closure, glomerular sclerosis, and interstitial fibrosis could also contribute to the clinical manifestations of this disorder.

The role of TGF-β and epithelial-to mesenchymal transition in diabetic nephropathy

“…Although the aetiology of Type I and Type II diabetes is notably distinct, glucose-evoked changes in renal physiology are almost indistinguishable and often lead to complete destruction of kidney function prompting the need for dialysis or transplantation therapy [2]. Multiple structural and functional changes are associated with the disease, specifically in the glomerulus, tubulointerstitium and vasculature [3], where glycaemic injury includes structural abnormalities ranging from hypertrophy, thickening of the glomerular basement membrane, tubular atrophy and interstitial fibrosis [4]. These changes contribute to increased glomerular filtration rate, proteinuria, systemic hypertension and the loss of renal function [4].…”

Heparanase induces a differential loss of heparan sulphate domains in overt diabetic nephropathy

“…Diabetic nephropathy is initially characterised by a minor increase in urinary excretion of albumin, called microalbuminuria, which generally progresses to macroalbuminuria or overt proteinuria with subsequent decline of glomerular function. Ultrastructural changes in diabetic nephropathy include mesangial matrix expansion and thickening of the glomerular and tubular basement membranes [7][8][9]. In addition, changes in GBM heparan sulphate content have been associated with the pathogenesis of diabetic nephropathy.…”

Are glomerular volume differences between type 1 and type 2 diabetic patients pathologically significant?

“…The development of glomerular and interstitial lesions is also common to the two types of diabetes [3][4][5][6]. However, the reported rate of progress varies, particularly in type 2 diabetic patients, where the decline in GFR can range from +3.1 to −22.0 ml min −1 year −1 [2,[7][8][9].…”