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CMAJ
CMAJ - May 30, 2000JAMC - le 30 mai 2000

Managing hypertension in patients with renal disease and diabetes

CMAJ 2000;162:1554-5

See response from: R.D. Feldman, et al
I congratulate the authors of the 1999 Canadian recommendations for the management of hypertension [Supplement]1 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.2–4 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.

Alan Bell
Family physician
Downsview, Ont.

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References
  1. Feldman RD, Campbell N, Larochelle P, Bolli P, Burgess ED, Carruthers SG, et al, for the Task Force for the Development of the 1999 Canadian Recommendations for the Management of Hypertension. 1999 Canadian recommendations for the management of hypertension. CMAJ 1999;161(12 Suppl):S1-22. [MEDLINE]
  2. Bakris GL, Weir MR, DeQuattro V, McMahon FG. Effects of an ACE inhibitor/calcium antagonist combination on proteinuria in diabetic nephropathy. Kidney Int 1998;54:1283-9. [MEDLINE]
  3. Bakris GL, Barnhill BW, Sadler R. Treatment of arterial hypertension in diabetic humans: importance of therapeutic selection. Kidney Int 1992;41:912-9. [MEDLINE]
  4. Bakris GL, Copley JB, Vicknair N, Sadler R, Leurgans S. Calcium channel blockers versus other antihypertensive therapies on progression of NIDDM associated nephropathy. Kidney Int 1996;50:1641-50. [MEDLINE]
  5. Tarif N, Bakris GL. Preservation of renal function: the spectrum of effects by calcium-channel blockers. Nephrol Dial Transplant 1997;12:2244-50. [MEDLINE]
  6. Guasch A, Parham M, Zayas CF, Campbell O, Nzerue C, Macon E. Contrasting effects of calcium channel blockade versus converting enzyme inhibition on proteinuria in African Americans with non-insulin-dependent diabetes mellitus and nephropathy. J Am Soc Nephrol 1997;8:793-8. [MEDLINE]
  7. Packer M, O'Connor CM, Ghali JK, Pressler ML, Carson PE, Belkin RN, et al. Effect of amlodipine on morbidity and mortality in severe chronic heart failure. N Engl J Med 1996;335:1107-14. [MEDLINE]
  8. Bianchi S, Bigazzi R, Baldari G, Campese VM. Long-term effects on enalapril and nicardipine on urinary albumin excretion in patients with chronic renal insufficiency: a 1-year follow-up. Am J Nephrol 1991;11:131-7. [MEDLINE]
  9. Zucchelli P, Zuccala A, Borghi M, Fusaroli M, Sasdelli M, Stallone C, et al. Long-term comparision between captopril and nifedipine in the progression of renal insufficiency. Kidney Int 1992;42:452-8. [MEDLINE]
  10. Perna A, Remuzzi G. Abnormal permeability to proteins and glomerular lesions: a meta-analysis of experimental and human studies. Am J Kidney Dis 1996;27:34-41. [MEDLINE]
  11. Maki DD, Ma JZ, Louis TA, Kasiske BL. Effects of antihypertensive agents on the kidney. Arch Intern Med 1995;155:1073-82. [MEDLINE]

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