Background:
The antiproteinuric effect of combining the angiotensin-converting enzyme (ace) inhibitor lisinopril and the angiotensin ii (ang ii) antagonist losartan was compared to that of the optimal antiproteinuric doses of monotherapy.
Methods:
To this purpose, lisinopril and losartan were studied in 9 nondiabetic renal patients with median proteinuria 4.5 g/day (95% ci, 3.5, 6.4), creatinine clearance of 80 ml/min (95% ci, 66, 96), and mean arterial pressure (map) of 102 mm hg (95% ci, 93, 112). first, in two protocols with six-week treatment periods per dose, the optimal antiproteinuric dose of each drug was established in each patient. losartan and lisinopril were used in randomized order, each preceded by a baseline period without medication. the doses of losartan (mg/day) were 50, 100, 150, and again 50. the lisinopril doses were 10, 20, 40, and again 10. after the second protocol, patients were treated with a combination, using the optimal antiproteinuric doses established for the individual drugs.
Results:
The antiproteinuric response by losartan was optimal at 100 mg (-46%; 95% ci, -60, -24%), being larger than at the 50 mg dose (-27%; 95% ci, -42, -4%, p < 0.05), but not different from the 150 mg dose (-46%; 95% ci, -58; -20%). proteinuria decreased further at each up-titration step of lisinopril to -75% (95% ci, -85, -43%) at the 40 mg dose. combination therapy reduced proteinuria more effectively (-85%; 95% ci, -96, -58) than monotherapy with losartan, and to a lesser extent than with lisinopril. optimal blood pressure responses were obtained at similar doses.
Conclusions:
Dose-titration with a renin-angiotensin system blocker, followed by add-on therapy is highly effective in order to reduce proteinuria. the safety of this regimen needs to be addressed in future studies.