Hemorheology, plasma protein composition and von Willebrand Factor in type I diabetic nephropathy

Patients with IDDM, especially those with albuminuria are at high risk for macrovascular and microvascular complications. Besides the major classic risk factors altered hemorheology may also play a role. Plasma viscosity, erythrocyte aggregation and erythrocyte deformability are the major determinants of blood flow in the microcirculation. Therefore, these hemorheological parameters and plasma protein composition were evaluated in 58 IDDM-patients with none (N0), incipient (N1: albuminuria 30-300 mg/day) and overt clinical nephropathy (N2: albuminuria >300 mg/day). As an estimate of endothelial injury plasma levels of von Willebrand Factor (vWF) were investigated. Patients with incipient and clinical nephropathy exhibited increasing blood levels of fibrinogen (N0=2.47+/-0.09, N1=2.71+/-0.15, N2=3.49+/-0.24 g/l, p <0.001), alpha(2)-macroglobulin (N0=257+/-11, N1=251+/-21, N2=382+/-43 mg/100 ml, p <0.01) and haptoglobin (N0=174+/-16, N1=216+/-39, N2=278+/-36 mg/100 ml, p <0.05), whereas serum albumin concentration decreased (N0=5.1+/-0.1, N1=4.7+/-0.1, N2=4.1+/-0.2 g/100 ml, p <0.001). In the same patients erythrocyte aggregation (N0=10.0+/-0.4, N1=12.1+/-0.5, N2=12.9+/-0.6, p <0.001), plasma viscosity (N0=1.34+/-0.01, N1=1.38+/-0.02, N2=1.40+/-0.02 mPas, p <0.05) and erythrocyte rigidity (N0=0.05+/-0.01, N1=0.15+/-0.05, N2=0.09+/-0.02, p <0.05) were increased, predominantly in those with overt clinical nephropathy. Erythrocyte aggregation was positively correlated with plasma concentrations of fibrinogen (r=0.65, p <0.001) and alpha(2)-macroglobulin (r=0.35, p <0.05), but negatively with plasma albumin concentration (r=-0.49, p <0.001). Plasma viscosity was positively correlated with plasma concentrations of fibrinogen (r=0.46, p <0.001) and haptoglobin (r=0.46, p <0.001). Von Willebrand Factor levels were higher in patients with overt clinical nephropathy (N0=126+/-8, N1=136+/-12, N2=163+/-14%, p <0.09, P-N0-N2 <0.05). A significant correlation between vWF and the rheological determinants could not be detected. These data demonstrate that blood rheology is profoundly altered in patients with IDDM and nephropathy. Elevated levels of vWF may indicate endothelial damage, and changes in plasma viscosity as well as erythrocyte aggregability seem to be the result of altered plasma protein composition due to proteinuria. These abnormalities in hemorheology may be an aggravating factor promoting microvascular and macrovascular damage in patients with type I diabetes mellitus and nephropathy.