Tight blood pressure control among diabetic and nondiabetic patients with
hypertension is perhaps the single most effective intervention used to delay progression to
end-stage renal disease (
ESRD). The renoprotective actions of
angiotensin-converting enzyme (
ACE) inhibitors in patients with diabetic and
hypertensive nephropathy is well established. Drugs of this class fairly uniformly reduce glomerulosclerosis, delay the deterioration in renal function, and improve
proteinuria, a predictive
surrogate marker for renal injury.
Calcium- channel blockers (CCBs) in the phenylalkylamine (
verapamil) and benzothiazepine (
diltiazem) classes also improve
proteinuria and delay the progression of renal disease in diabetic and nondiabetic
hypertensive nephropathy beyond that attributable to blood pressure control. The short-acting
dihydropyridine CCBs worsen
proteinuria and accelerate renal injury in both animal models and humans with
hypertension or diabetes. A very limited number of studies in animals or humans with
hypertension or diabetes have demonstrated at least an additive renoprotective effect when the combination of
ACE inhibitors and nondihydropyridine CCBs has been compared with each agent administered as monotherapy. Because patients with impaired renal function and either
hypertension or diabetes appear to benefit from aggressive blood pressure reduction, many of these patients will require two or more drugs to achieve the currently recommended blood pressure goals. Combinations of
ACE inhibitor and CCB are attractive because they may provide better blood pressure control, appear to be better tolerated with fewer side effects than either
drug alone, and may exert a greater renoprotective effect in patients at risk for
renal failure than either an
ACE inhibitor or a CCB.