Improvement of glomerular size-selective function by ace inhibition
and aii receptor blockade in iga nephropathy.
Remuzzi, Andrea, Norberto Perico, Fabio Sangalli, Giovanni Vendramin,
Monica Moriggi, Piero Ruggenenti and Giuseppe Remuzzi.
1Department of Kidney Research, Mario Negri Institute for
Pharmacological Research, Bergamo, Italy, 2Unit of Nephrology and
Dialysis, Ospedali Riuniti di Bergamo, Bergamo, Italy, 3Unit of
Nephrology and Dialysis, Ospedale Treviglio-Caravaggio, Treviglio,
Italy
APStracts 5:0207F, 1998.
Protein trafficking across the glomerular capillary has a pathogenic
role in subsequent renal damage. Despite evidence that angiotensin
-converting enzyme (ACE) inhibitors improve glomerular size
-selectivity, if this effects is due to angiotensinn II (AII) blocking
or whether other mediators also play a contributory role is not clear
yet. We then studied 20 proteinuric patients with IgA nephropathy
randomized to receive enalapril (20 mg/day) or the AII receptor
blocker irbesartan (100 mg/day) for 28 days, as single
administration, 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 after 28
days of treatment. Both enalapril or irbesartan significantly reduced
blood pressure over baseline. This reduction, however, reached the
maximum effect 4-6 hours after drug administration, but did not last
for the entire 24 hour period. Despite transient antihypertensive
effect, proteinuria was effectively reduced by both treatments at
comparable extent. Neither enalapril nor irbesartan modified the
sieving coefficients of small dextran molecules but effectively
reduced transglomerular passage of largest test macromoleules.
Theoretical analysis of sieving coefficients showed that both drugs
did not affect significantly the mean pore radius and the spread of
the pore-size distribution, but importantly and comparably reduced
the importance of a non-slective shunt pathway. These data suggest
that antagonism of AII is the key mechanism by which ACE inhibitors
exert their beneficial effect on glomerular size-selective function
and consequently on glomerular filtration and urinary output of
plasma proteins.
Received 22 June 1998; accepted in final form 17 November 1998.
APS Manuscript Number F154-8.
Article publication pending Am. J. Physiol. (Renal Physiology).
ISSN 1080-4757 Copyright 1998 The American Physiological Society.
Published in APStracts on 9 December 1998