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 ki dney disease, we measured the renal clearances of albumin, total IgG, and IgG4 in 20 male Type 2 (non-insulin-dependent) diabetic patients w ith diabetic glomerulosclerosis (biopsy proven), in 10 male Type 2 dia betic patients without nephropathy (urinary albumin excretion rate I 3 0 mg/24 h), and in 10 healthy male subjects. The fractional clearance of albumin was increased in patients with nephropathy: 659 (42-4355).1 0(-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 o ther groups. The IgG/IgG4 selectivity index was not significantly diff erent in the three groups, being: 1.12 (0.06-5.65), 1.16 (0.45-3.72) a nd 1.35 (0.65-3.34) in patients with nephropathy, patients without nep hropathy, and healthy subjects, respectively. The IgG/albumin selectiv ity 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 < 0.0 01) 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 systoli c 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 < 0.00 5). The diastolic blood pressure was higher in patients with and witho ut 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 im paired barrier size selectivity, probably due to an increase in large pore area (''shunt pathway'') in the glomerular capillary wall and sys temic hypertension are the major pathogenic mechanisms of proteinuria in Type 2 diabetic patients with diabetic nephropathy.