SELECTIVE DECREMENT OF ANIONIC IMMUNOGLOBULIN CLEARANCE AFTER INDUCED RENAL HEMODYNAMIC-CHANGES IN DIABETIC-PATIENTS

The charge permselectivity of proteins was evaluated in diabetic patients after systemic and renal hemodynamic changes induced by an intravenous injection of an angiotensin-converting enzyme inhibitor (captopril) or of clonidine. Anionic immunoglobulin clearance (IgG4) was compared with that of total immunoglobulins, which have the same size but are mostly cationic, and of albumin. Ten type 1 hypertensive diabetic patients (group 1), 10 type 2 hypertensive diabetic patients (group 2), 5 type 1 normotensive diabetic patients (group 3), 10 subjects with essential hypertension (group 4), and 7 normal volunteers (group 5) received an intravenous injection of captopril (25 mg/100 ml in 5 min). Twelve of the hypertensive diabetic patients underwent a second provocative test with clonidine (150-mu-g/100 ml) (group 6) or placebo (100 ml saline) (group 7) with the same procedure. None of the patients had clinical nephropathy or other disorders. Glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured before and during the tests. A significant decrease in diastolic blood pressure was observed in groups 1, 2, 4, and 6, together with an increase in the GFR and RPF values in groups 1, 2, 3, and 4 only, as well as a decrease in renal vascular resistances in groups 1, 2, 3, 4, and 6. Both clearances and fractional clearances of IgG4 and IgG decreased after captopril in groups 1 and 2. The decrease in IgG4 clearance was correlated to that of renal vascular resistances in group 1 patients. A significant decrease in the anionic/cationic immunoglobulin ratio (IgG4/IgG) was observed in groups 1, 2, and 3. Thus the renal hemodynamic modifications associated with captopril, but not with clonidine or placebo, unmasked a charge selectivity impairment of protein filtration in diabetic patients without clinical signs of diabetic kidney disease.