ACE inhibition and ANG II receptor blockade improve glomerular size-selectivity in IgA nephropathy

Protein trafficking across the glomerular capillary has a pathogenic role i n subsequent renal damage. Despite evidence that angiotensin-converting enz yme (ACE) inhibitors improve glomerular size-selectivity, whether this effe ct is solely due to ANG II blocking or if other mediators also play a contr ibutory role is not clear yet. We studied 20 proteinuric patients with IgA nephropathy, who received either enalapril (20 mg/day) or the ANG II recept or blocker irbesartan (100 mg/day) for 28 days in a randomized double-blind study. Measurements of blood pressure, renal hemodynamics, and fractional clearance of neutral dextran of graded sizes were performed before and afte r 28 days of treatment. Both enalapril and irbesartan significantly reduced blood pressure over baseline. This reduction reached the maximum effect 4- 6 h after drug administration but did not last for the entire 24-h period. Despite transient antihypertensive effect, proteinuria was effectively redu ced by both treatments to comparable extents. Neither enalapril nor irbesar tan modified the sieving coefficients of small dextran molecules, but both effectively reduced transglomerular passage of large test macromolecules. T heoretical analysis of sieving coefficients showed that neither drug affect ed significantly the mean pore radius or the spread of the pore-size distri bution, but both importantly and comparably reduced the importance of a non selective shunt pathway. These data suggest that antagonism of ANG II is th e key mechanism by which ACE inhibitors exert their beneficial effect on gl omerular size-selective function and consequently on glomerular filtration and urinary output of plasma proteins.