Role of mesangial expansion in the pathogenesis of diabetic nephropathy.

Glomerulopathy, characterized by thickening of the glomerular basement membrane (GBM) and mesangial expansion, is the most important renal structural change in type 1 diabetic patients with diabetic nephropathy. Morphological lesions develop concomitantly in the arterioles, tubules and interstitium. Mesangial fractional volume [Vv(mes/glom)], an estimate of mesangial expansion, is the structural parameter that best correlates with glomerular filtration rate (GFR) and it is also closely related to the presence of proteinuria and hypertension. Diabetic glomerulopathy has also been described in type 2 diabetic patients, but glomerular lesions are milder than in type 1 diabetic patients. In type 2 diabetes glomerular structural parameters are, on average, altered. However, despite persistent microalbuminuria or proteinuria, several patients have normal glomerular structure. Renal structure is, in fact, heterogeneous in type 2 diabetic patients: only a subset has typical diabetic glomerulopathy, while a substantial proportion has more advanced tubulo-interstitial and vascular rather than glomerular lesions, or has normal or near normal renal structure. Also in type 2 diabetes mesangial expansion is related to renal functional parameters, but although significant, these structural-functional relationships are less precise than in type 1 diabetes. Thus, both in type 1 and in type 2 diabetes, mesangial expansion is the most important structural change. Finally, we have recently demonstrated that, the lesions of diabetic glomerulopathy can be reversed in humans. This amelioration in glomerular structure was observed after long-term normoglycemia obtained by pancreas transplantation. This is a new concept in nephrology, and the understanding of the mechanisms involved in the glomerular architectural remodelling might have important clinical and therapeutic implications.