Von Willebrand factor abnormalities in IgA nephropathy

BACKGROUND: Plasma concentration of von Willebrand factor (vWF) has beenused as an index of endothelial dysfunction. Increased release of vWF fromendothelial cells has been reported in several conditions, and there isalso evidence that dysfunctioning endothelial cells synthesize defectivemolecules. In fact, unusually large vWF multimers have been described andrelated to the pathogenesis of some microangiopathic diseases. Abnormallevels of vWF have been reported in primary glomerulitis, but this was noreferred to histological diagnosis. Furthermore, no qualitative vWFanalysis was performed in these glomerulopathies. Therefore the aim of ourstudy was to analyse quantitatively and qualitatively vWF in patients withIgA (IgAN) and non-IgA mesangial proliferative glomerulonephritis (PGN).METHODS: Fourteen IgAN patients, eight PGN patients, seven subjects withdifferent glomerulonephritides, and 10 healthy controls formed the basis ofthis study. On peripheral venous blood collected in the presence ofprotease inhibitors, vWF parameters were investigated. vWF antigenicactivity (vWF:Ag) was measured by electroimmunodiffusion. vWF subunitsmobility was studied by crossed immunoelectrophoresis (CIE) and in somepatients vWF multimeric analysis was performed by SDS- agarose gelelectrophoresis. RESULTS: Mean vWF:Ag was significantly higher in PGNpatients as compared to controls, while there was no significant differencebetween PGN and IgAN patients and between IgAN and controls. CIE revealed apre-peak in 12 of 14 IgAN patients and a migration index which did notdiffer between controls, IgAN, and PGN subjects. No pre-peak was observedin PGN and in other glomerulonephritides. Analysis of plasma vWF multimericpattern by SDS- agarose gel electrophoresis disclosed in four IgAN patientsabnormally large vWF multimers that were not documented in PGN subjects.CONCLUSIONS: This study, by showing the presence of a pre-peak and of largevWF multimers in IgAN patients, suggests an altered postsecretory handlingof the vWF in IgAN and possibly a different role of the vWF in IgAN inrespect to PGN.