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Over the past two decades numerous studies have evaluated the effects of angiotensin converting enzyme (ACE) inhibitors and calcium antagonists on proteinuria and the progression of diabetic renal disease. Taken together, these studies suggest that certain types of calcium antagonists and ACE inhibitors have distinctive advantages over conventional antihypertensive agents with regard to improving overall and renal survival. Among the unique actions of these two classes of drugs are their effects on matrix proteins apart from their effects in reducing arterial pressure.There is no definitive answer to the question of whether the effects of ACE inhibitors and calcium antagonists are additive when the drugs are used together. However, preliminary data from both animal and clinical studies suggest that combinations of non-dihydropyridine calcium antagonists and ACE inhibitors produce an additional fall in proteinuria and have more favorable side effect profiles than results observed with either drug alone. Therefore, combination therapy with these agents may be valuable, especially in diabetic patients with renal insufficiency in whom arterial pressure is difficult to control.