Antiproteinuric effect of blood-pressure-lowering agents: a meta-analysis of comparative trials

Whether ACE inhibitors (ACEi) differ from other antihypertensives in their efficacy to lower proteinuria is controversial. We therefore performed a meta-analysis of articles on this subject. The secondary objective in our meta-analysis was to study whether there is any difference between diabetic and non-diabetic patients in antiproteinuric response to blood pressure reduction. To identify all articles we performed a computer search using the bibliographic databases. To minimize publication bias, only trials in which a direct comparison was made between an ACEi and another antihypertensive were included. Studies performed both in diabetic and in non-diabetic patients were eligible. Included were 41 studies, comprising 1124 patients, of which 558 had non-diabetic renal disease. The mean antiproteinuric effect of ACEi was significantly greater than that of their comparator drugs: -39.9% (95% confidence interval: -42.8 to 36.8%) versus -17.0% (-19.0 to -15.1%) respectively (difference 24% (19.5 to 28.6%)). The blood-pressure-lowering effect was equal: -12.0% (-12.8 to -11.2%) versus -11.4% (-11.7 to -11.1%) respectively (difference -0.8% (-1.8 to 0.2%)). Thus it may be concluded that ACEIs confer an antiproteinuric effect beyond that attributable to their blood-pressure-lowering effect. A wide interstudy variation in antiproteinuric response to non-ACEI antihypertensives was observed. Multiple variable regression analysis was performed to assess which factors may explain this heterogeneity. From the comparator drugs, the class was of no importance: calcium-channel antagonists (CCA), beta-blockers, and a rest group of other drug types showed a similar response. Patient characteristics such as initial GFR and blood pressure partly explained the variation in response, but most of it appeared dependent on the blood pressure reduction achieved. Furthermore the type of CCA is of importance, with nifedipine having the least effect. A significantly greater antiproteinuric effect of 'non-ACEI' antihypertensives was found in diabetic patients compared to non-diabetics. However, this coincided with a greater blood pressure reduction in diabetics. Adjusted for differences in blood pressure control, diabetics showed even a slightly lesser antiproteinuric response to non-ACEI antihypertensive compared to non-diabetics.