Lehnert T, Lubrich-Birkner I, Dreyling K, Schollmeyer P
Effects of captopril and diltiazem on
proteinuria: A crossover double-blind study
Am Soc Nephrol
J Am Soc Nephrol (abstract)
(Sep) 7:1322 1996
The potential benefits of the available classes of antihypertensive
agents on proteinuria are hotly debated. It has been shown that
ACE-inhibitors do provide renal protection in insulin dependent
nephropathy. The effects of calcium channel blockers on proteinuria in
both diabetic and nondiabetic renal diseases have been variable. The
specific effects of non-dihydropyridine calcium channel blockers is
not well studied.
The authors performed a pilot project with 20 patients enrolled in a
double blind crossover study comparing captopril (25 mg TID) and
diltiazem (90mg TID). The patients were all hypertensive and had both
diabetic and nondiabetic proteinuria (minimum 0.5 gm/day). After a 2
week run-in (antihypertensives allowed except calcium channel blockers
and ACE-inhibitors), the patients were randomized to either therapy
for six weeks and then washed out for 2 weeks and then placed on the
other treatment arm for six weeks. Urinary prtoein measurements were
done every 2 weeks.
The study group had mean protein loss of 2.7 gms/day and had serum
creatinine of 1.3mg/dl and mean arterial pressure of 115mmHg. Blood
pressure reduction was similar for the two groups (5.3 ñ 2.4 mmHg vs
5.1 ñ 2.1 mmHg, p = ns). Captopril reduced proteinuria significantly
below baseline at weeks 2, 4 and 6(at week 6, by 0.8 ñ 0.26 g/day).
Diltiazem had no effects on proteinuria.
Comment: This study suggests that in a group of
patients with both diabetic and nondiabetic proteinuria, captopril but
not diltiazem reduced proteinuria despite equivalent reductions in
blood pressure. These results are interesting but are limited. The 2
week washout is inadequate to perform a study like this since many
drugs have effects on proteinuria that persist for several weeks.
Secondly, the study sample is very small and the end points soft. It
is important that randomized trials examining the effects of
ACE-inhibitors and other drugs on renal function be conducted for
several years and have accurate GFR and protein measurements. It is no
assurance in any study that reduction of proteinuria and GFR
stabilization occur simultaneously. In the interim, it is not
unreasonable that the drugs of choice for diabetic proteinuria remain
ACE-inhibitors.
(George Mansoor, M.D., University of Connecticut)
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Am Soc Nephrol
H: Pathophysiology :
Kidney in hypertension
H: Drug therapy :
Calcium channel blockers