Bakris GL, Weir M, De Quattro V, Rosendorff C, McMahon G
Renal hemodynamic and antiproteinuric response to an ACE
inhibitor (trandolapril) or calcium antagonist (verapamil) alone or in
fixed dose combination in patients with diabetic nephropathy
Am Soc Nephrol
J Am Soc Nephrol (abstract)
(Sep) 7:1546 1996
Proteinuria is a risk factor for subsequent progression of renal
failure in many forms of renal disease and recent studies suggest ways
in which various filtered proteins could exacerbate renal disease. In
patients with type I and type II diabetic nephropathy, proteinuria is
a hallmark of advanced structural disease and is a harbinger of
progression in most cases.
Whereas ACE inhibitors have been shown to reduce proteinuria and
protect renal function in diabetics, particularly those with type I
nephropathy, the effects of calcium channel blockers on proteinuria
have been more varied. Dihydropyridines such as nifedipine have been
reported to increase proteinuria in some studies whereas verapamil and
diltiazem have been reported to decrease proteinuria to a similar
extent as ACE inhibitors.
In this study the authors examined the hypothesis that the fixed
combination of the ACE inhibitor trandolapril with verapamil would
reduce proteinuria in type II diabetics with nephropathy to a greater
extent than either trandolapril or verapamil alone. They point out
that these two agents have divergent effects on renal hemodynamics but
that both can reduce proteinuria. Accordingly, they measured baseline
renal hemodynamics, blood pressure and protein excretion rate in 39
type II diabetics with nephropathy then randomized the patients into
three groups: 1) trandolapril; 2) verapamil and 3) trandolapril plus
verapamil and measured GFR, RPF and proteinuria every 3 months for 12
months. Patients were maintained on a low sodium, low protein diet
throughout the period of study. Baseline BP was elevated and baseline
GFR and RPF were reduced.
They found that either drug alone or in combination normalized blood
pressure (<140/90) but none of the regimens altered GFR or RPF
significantly. In contrast, protein excretion was lowered about 40%
in the single agent groups but by 70% in the combination of
trandolapril plus verapamil, a difference that was significantly
different compared to either drug alone. Furthermore, because the
change in blood pressure from baseline and the and mean level after 12
months were not different between groups, the authors suggest that the
anti-proteinuric effect of the fixed combination of trandolapril and
verapamil may be due to changes in glomerular permeability.
Comment: The data from the study are provocative. The abstract
does not supply information concerning the levels of dietary sodium and
protein.
Variability in these could influence differences observed in groups.
It is also interesting that there were no detectable differences in
GFR at 1 year in any group. Thus the divergent effects on renal
hemodynamics between ACE inhibitors and verapamil claimed by the
authors were not apparent at 1 year. Perhaps these occurred at 3
months then disappeared later (again data not presented). Still, this
is an interesting finding and if confirmed would strengthen the
argument for using the combination of an ACE inhibitor with a
non-dihydropyridine calcium channel blocker in patients with type II
diabetes.
(Robert D. Toto, M.D., University of Texas Southwestern Medical
Center)
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Am Soc Nephrol
H: Pathophysiology :
Kidney in hypertension
CRF by problem area :
Progression