GLOMERULAR SIZE-SELECTIVITY AND CHARGE-SELECTIVITY IN TYPE-2 (NON-INSULIN-DEPENDENT) DIABETIC-PATIENTS WITH DIABETIC NEPHROPATHY

In an attempt to evaluate the mechanisms of proteinuria in diabetic kidney disease, we measured the renal clearances of albumin, total IgG, and IgG4 in 20 male Type 2 (non-insulin-dependent) diabetic patients with diabetic glomerulosclerosis (biopsy proven), in 10 male Type 2 diabetic patients without nephropathy (urinary albumin excretion rate I 30 mg/24 h), and in 10 healthy male subjects. The fractional clearance of albumin was increased in patients with nephropathy: 659 (42-4355).10(-6) (median (range)), compared to 2.6 (0.2-14.2).10(-6) in patients without nephropathy, and 2.3 (0.4-4.2).10(-6) in healthy subjects. The fractional clearance of total IgG (neutral) and of IgG4 (anionic) was 40-50 times higher in patients with nephropathy compared to the two other groups. The IgG/IgG4 selectivity index was not significantly different in the three groups, being: 1.12 (0.06-5.65), 1.16 (0.45-3.72) and 1.35 (0.65-3.34) in patients with nephropathy, patients without nephropathy, and healthy subjects, respectively. The IgG/albumin selectivity index was decreased in patients with nephropathy: 0.27 (0.01-1.26) compared to 1.29 (0.07-2.67) (p < 0.05) and 1.23 (0.76-7.84) (p < 0.001) in patients without nephropathy and healthy subjects, respectively. No significant change in IgG/albumin selectivity index was observed between patients without nephropathy and healthy subjects. The systolic blood pressure was elevated in the patients with nephropathy: 164+/-21 mm Hg (mean +/- SD) compared to patients without nephropathy: 145+/-20 mm Hg (p < 0.05) and to healthy subjects: 133+/-19 mm Hg (p < 0.005). The diastolic blood pressure was higher in patients with and without nephropathy: 92+/-7 vs 90+/-10 mm Hg compared to 79+/-8 mm Hg (p < 0.005) in healthy subjects. Our cross-sectional study suggests that impaired barrier size selectivity, probably due to an increase in large pore area (''shunt pathway'') in the glomerular capillary wall and systemic hypertension are the major pathogenic mechanisms of proteinuria in Type 2 diabetic patients with diabetic nephropathy.