Managing hypertension in patients with renal disease and diabetes

I congratulate the authors of the 1999 Canadian recommendations for the management of hypertension1 for their diligent work, but question the recommendations regarding hypertensive patients with diabetic and nondiabetic renal disease. Ample evidence exists to support the use of angiotensin-converting- enzyme (ACE) inhibitors as first-line agents in both of these circumstances, but the selection of dihydropyridine calcium-channel blockers as an alternative therapy for nondiabetic renal disease and the lack of a recommendation for the use of nondihydropyridines in diabetic nephropathy are questionable.

A number of well-designed studies have demonstrated that the reduction of proteinuria and preservation of renal function by nondihydropyridines, particularly verapamil, is similar to that by ACE inhibitors in diabetic nephropathy.2^,3^,4 These studies further indicate that the reduction of proteinuria by nondihydropyridines is additive to the effect of ACE inhibitors.

In contrast, studies using dihydropyridines have failed to demonstrate a benefit with regard to proteinuria or renal function unless systolic blood pressure is reduced below 110 mm Hg.5 Furthermore, several trials have demonstrated a renal hazard associated with the use of dihydropyridines in diabetic nephropathy and other situations. Isradipine was associated with a 50% increase in proteinuria in African Americans with diabetic nephropathy.6 In the PRAISE trial 7.7% of subjects randomized to receive amlodipine had worsening renal function compared with 3.6% in the placebo group.7

The guidelines cite studies by Bianchi and colleagues and Zucchelli and colleagues in support of the recommendation for the use of dihydropyridines in nondiabetic renal failure.8^,9 Although in these 2 studies an ACE inhibitor and a dihydropyridine produced similar changes in renal function, the effects with respect to proteinuria and renal death were significantly better with the ACE inhibitor.

Loss of renal autoregulation has been suggested as one mechanism for the unfavourable effects seen with the dihydropyridines.10 Because nondihydropyridine calcium-channel blockers do not impair renal autoregulation,11 have a favourable effect on glomerular permeability and have been demonstrated to be renal protective in clinical studies previously cited, they may be a better choice as an alternative therapy in diabetic and nondiabetic nephropathy and perhaps in all diabetic patients with hypertension.

Competing interests: Dr. Bell serves as a medical consultant to Searle Canada; he has received speaker fees and travel assistance grants.