Long-term antiproteinuric effect of dual renin-angiotensin system blockade

We evaluated the long-term changes on overt proteinuria induced by dual blockade of the renin-angiotensin system (RAS). Dual blockade was produced by adding an angiotensin II receptor blocker (ARB) to treatment with maximal recommended doses of an angiotensin converting enzyme (ACE) inhibitor in proteinuric patients. A total of 28 patients (19 men and 9 women) with proteinuria higher than 1 g/24 h were enrolled in this trial of treatment with the ARB candesartan (from 4 up to 32 mg daily) added to existing treatment with an ACE inhibitor. At 6, 12, 24, and 36 months, we evaluated proteinuria in 24-h urinary collections, office blood pressure (BP), plasmatic creatinine (Cr), serum potassium (K), and 24 h urine collection creatinine clearance (CrC). During monoblockade of the RAS by ACE inhibitor treatment, albuminuria was 2.94 +/- 1.92 mg/24 h; BP was 137/76 mmHg; K+ was 4.8 +/- 0.5 mmol/l, Cr was 1.76 +/- 0.67 mg/dL, and CrC was 62 +/- 31.9 mL/min. After 6 months, dual blockade of the RAS albuminuria was 2.18 +/- 2.29 mg/24 h (P < 0.01 vs. baseline) and BP was 133/75 mmHg (not significant). At 36 months, albuminuria was 2.21 +/- 2.20 mg/24 h (P < 0.05 vs. baseline); BP was 133/73 mmHg (not significant). CrC was not changed along the follow up. A small increment of Cr was detected at 24 months (2.11 +/- 1.06 mg/mL, P < 0.05). The antiproteinuric effect of dual renin-angiotensin system blockade combining candesartan and ACE inhibitors remain after 36 months without losing its initial effect. Blood pressure changes seem not to explain this long-term antiproteinuric effect.