Comparative Study of the Effect of ACE-Inhibitors and Other Antihypertensive Agents on Proteinuria in Diabetic Patients

Several studies during the past 15 years have shown that antihypertensive therapy with different types of drugs can reduce microalbuminuria or clinical proteinuria and retard the progression toward end-stage renal failure. However, some authors reported disparate renal protective effects of different antihypertensive drugs in diabetic animals and humans. In an attempt to resolve the controversy surrounding this possibility, previously we reported a meta-analysis of published studies in diabetics with microalbuminuria or overt proteinuria treated with conventional agents, angiotensin-converting enzyme (ACE) inhibitors, or calcium antagonists (Ca2+ antagonists). Here we present an updated meta-analysis of published studies in diabetics with microalbuminuria or clinical proteinuria (UProt), treated during ≥ 4 weeks with ACE inhibitors, Ca2+ antagonists, or conventional therapy (diuretic and/or β-blocker). Despite similar blood pressure (BP) reductions, UProt tended to decrease more on ACE inhibitors (on average -45%) than on conventional therapy (on average -23%) or Ca2+ antagonists other than nifedipine (on average -35%); in contrast, UProt tended to increase slightly on nifedipine (on average 5%, P 5% and the slope was steeper (4% UProt change per percent BP change) than on ACE inhibitors. On Ca2+ antagonists other than nifedipine, UProt was unchanged at zero BP change, and the regression line for the relationship between changes in UProt (r = 0.55, P < .05) was in an intermediate position between ACE inhibitors and conventional treatment. Seventy reports also contained data on glomerular filtration rate (GFR). On ACE inhibitors, GFR was on average unchanged, but tended to increase slighty with progressive BP reduction (r = -0.55, P < .0001). On conventional therapy or Ca2+.antagonists, variations in GFR were unrelated to changes in BP. As ACE inhibitors exert a specific antiproteinuric effect even without a change in systemic BP, they are superior to other agents in treating microalbuminuria or overt proteinuria in initially normotensive or mildly hypertensive diabetic patients. On the other hand, when systemic BP can be lowered by 20%, as it is desirable in severely hypertensive patients, ACE inhibitors, conventional therapy, and several Ca2+ antagonists all have a distinct antiproteinuric action. In contrast, as the example of nifedipine illustrates, drug-specific intrarenal effects may antagonize a BP-dependent antiproteinuric action and even counteract the effect of lowering systemic pressure. It is of note that ACE inhibitors may, in addition to their antiproteinuric effect, exert a drug-specific beneficial influence on GFR. Am J Hypertens 1994;7:84S-92