EFFECTS OF AN ACE-INHIBITOR CALCIUM-ANTAGONIST COMBINATION ON PROTEINURIA IN DIABETIC NEPHROPATHY

Background. The degree of proteinuria in patients with diabetes correl ates strongly with both an increase in progression of nephropathy as w ell as cardiovascular events. Moreover, post hoc analyses of recent cl inical trials support the concept that reductions of blood pressure an d proteinuria correlate with a slowed progression of nephropathy. Both angiotensin converting enzyme (ACE) inhibitors and the nondihydropyri dine calcium antagonists, (non-DHPCAs) reduce both arterial pressure a nd proteinuria in those with diabetic nephropathy. Methods. The presen t randomized, open label, parallel group designed study tests the hypo thesis that, at similar levels of blood pressure, the combination of a n ACE inhibitor, trandolapril (T) with the non-DHPCA, verapamil (V) pr oduces a greater reduction in proteinuria over either agent alone at o ne year. Thirty-seven participants, mean age 59.6 +/- 5.8 years, with nephropathy (baseline creatinine 1.4 +/- 0.3 mg/dl and proteinuria of 1342 +/- 284 mg/dl) secondary to type 2 diabetes completed the study. Doses of drug were titrated in each group over eight weeks to achieve a goal blood pressure of < 140/90 mm Hg. All participants were counsel ed to ingest a sodium diet of < 120 mEq/day. Results. Proteinuria redu ction from baseline was significantly greater in the T+V group compare d to either T alone (-33 +/- 8%,, T vs. -62 +/- 10%, T+V; P < 0.001) o r V alone (-27 +/- 8%, V vs. -62 +/- 10%, T+V; P < 0.001). No signific ant differences in either glomerular filtration rate, arterial pressur e, fasting blood glucose or urinary sodium excretion were noted at one year. The mean daily dose of the individual components of T+V (2.9 +/ - 0.8 mg, T/219 +/- 21.1 mg V) was significantly lower than the dose o f either T alone 5.5 +/- 1.1 mg/day (P < 0.01) or V alone 314.8 +/- 46 .3 mg, given in two divided doses (P < 0.01). Conclusion. These data s upport the concept that the combination of an ACE inhibitor with a non -DHPCA reduce proteinuria to a greater extent than either agent alone. This added antiproteinuric effect occurs at lower doses of each drug and is independent of further reductions in arterial pressure. These f indings could have ramifications fur slowing renal disease progression in patients with nephropathy from type 2 diabetes.