VON-WILLEBRAND-FACTOR ABNORMALITIES IN IGA NEPHROPATHY

Background. Plasma concentration of von Willebrand factor (vWF) has be en used as an index of endothelial dysfunction. Increased release of v WF from endothelial cells has been reported in several conditions, and there is also evidence that dysfunctioning endothelial cells synthesi ze defective molecules. In fact, unusually large vWF multimers have be en described and related to the pathogenesis of some microangiopathic diseases. Abnormal levels of vWF have been reported in primary glomeru litis, but this was no referred to histological diagnosis. Furthermore , no qualitative vWF analysis was performed in these glomerulopathies. Therefore the aim of our study was to analyse quantitatively and qual itatively vWF in patients with IgA (IgAN) and non-IgA mesangial prolif erative glomerulonephritis (PGN). Methods. Fourteen IgAN patients, eig ht PGN patients, seven subjects with different glomerulonephritides, a nd 10 healthy controls formed the basis of this study. On peripheral v enous blood collected in the presence of protease inhibitors, vWF para meters were investigated. vWF antigenic activity (vWF:Ag) was measured by electroimmunodiffusion. vWF subunits mobility was studied by cross ed immunoelectrophoresis (CIE) and in some patients vWF multimeric ana lysis was performed by SDS-agarose gel electrophoresis. Results. Mean vWF:Ag was significantly higher in PGN patients as compared to control s, while there was no significant difference between PGN and IgAN pati ents and between IgAN and controls. CIE revealed a pre-peak in 12 of 1 4 IgAN patients and a migration index which did not differ between con trols, IgAN, and PGN subjects. No pre-peak was observed in PGN and in other glomerulonephritides. Analysis of plasma vWF multimeric pattern by SDS-agarose gel electrophoresis disclosed in four IgAN patients abn ormally large vWF multimers that were not documented in PGN subjects. Conclusions. This study, by showing the presence of a pre-peak and of large vWF multimers in IgAN patients, suggests an altered postsecretor y handling of the vWF in IgAN and possibly a different role of the vWF in IgAN in respect to PGN.