Glomerular structural changes in Type 1 (insulin-dependent) diabetes mellitus: causes, consequences, and prevention

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Abstract
Diabetic nephropathy is caused primarily by advanced glomerulopathy, the renal expression of diabetic microangiopathy. With stereological methods a quantitative description of the structural changes is achieved. The glomerulopathy is characterized by an increase in basement membrane material: thickening of the capillary wall and an increase in mesangial volume relative to glomerular volume, comprising increase in matrix. Among groups of patients conformity between renal function stage and structure exists. The parameters measuring glomerulopathy are normal at the onset of diabetes; patients with normoalbuminuria may show slight basement membrane thickening, or normal parameters; the microalbuminuric group shows a measurable, but moderate glomerulopathy; patients with overt nephropathy have advanced lesions; at this stage heterogeneity among glomeruli makes the estimates weaker. Recent data indicate that the changes in peripheral basement membrane and in mesangial matrix develop in concert and both contribute to the early stage of glomerulopathy in patients with microalbuminuria. As to the consequences of the structural changes the mechanism of albuminuria is not clear. It is suggested that the early glomerulopathy entails other structural modifications, including formation of new vessels which may be the site of leakage. The marked deviations in glomerular filtration rate correspond well with estimates of filtration surface area: in the early hyperfunction state it is increased; in advanced nephropathy it is decreased, due to advanced glomerulopathy in conjunction with glomerular occlusion. The diabetic state is the necessary condition for the glomerulopathy. In relating structural changes to presumed contributing causes no supporting evidence of a relationship with glomerular hyperfunction or hypertrophy was observed. The structural parameters may be useful tools in clinical trials aiming at arresting the development of glomerulopathy, and thereby providing a prevention of diabetic nephropathy.