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 < or = 30 mg/24 h), and in 10 healthy male subjects. The fractional clearance of albumin was increased in patients with nephropathy: 659 (42-4355) x 10(-6) (median (range)), compared to 2.6 (0.2-14.2) x 10(-6) in patients without nephropathy, and 2.3 (0.4-4.2) x 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).(ABSTRACT TRUNCATED AT 250 WORDS)