Quantitative changes in the glomerular basement membrane components in human membranous nephropathy

In membranous nephropathy (MN), the glomerular basement membrane (GBM) is thickened due to accumulation of GBM material between and around the subepithelial immune deposits. Alterations in the GBM components in relation to subepithelial deposits and GBM thickening are not clearly defined. The GBM distribution of classical and novel [alpha 4(IV)] chains of type IV collagen, laminin, and fibronectin have been studied in seven patients with MN and in three normal controls by a quantitative immunogold technique. In normal kidneys, the labelling of type IV collagen or fibronectin was distributed predominantly along the endothelial side of the GBM; alpha 4(IV) was found in the lamina densa; and laminin was concentrated in the epithelial zone of the GBM (P < 0.01). In MN, there were increased immunogold densities for classical and novel type IV collagen chains, laminin, and fibronectin in the spikes of MN patients compared with controls (P < 0.05). Furthermore, gold particle labelling for the alpha 4(IV) collagen chain was increased in the middle zone (P < 0.01) and that for fibronectin was increased in the endothelial and middle zones of the GBM (P < 0.05) compared with normal controls. These findings suggest that subepithelial immune deposits stimulate glomerular epithelial cells (GEC), resulting in enhanced secretion of classical and novel type IV collagen chains, laminin, and fibronectin, forming spikes in MN; of these newly formed components, only novel type IV collagen appears to migrate towards the middle zone of the GBM, contributing to thickening of this zone. The results also suggest that fibronectin, possibly derived from the circulation, is related to thickening of the endothelial zone of the GBM, which in turn might be related to progressive glomerulosclerosis.