Dissociation between blood pressure reduction and fall in proteinuria in primary renal disease: A randomized double-blind trial

Abstract

Objective: Guidelines recommend lower threshold and goal blood pressure (BP) for patients with proteinuria. BP reduction could be accompanied by a different fall in proteinuria depending of the antihypertensive drug. The objective was to compare proteinuria reduction when BP is lowered to the same level with different drugs.

Design: Prospective, randomized, double-blind, controlled trial.

Setting: 12 Spanish centres.

Patients: A total of 119 patients with primary renal disease, blood pressure > 130/85 mmHg, proteinuria > 1 g/day, and creatinine clearance > or = 50 ml/min.

Intervention: After a 4-week run-in placebo period, patients were randomized to: atenolol 50 mg/day; trandolapril 2 mg/day; verapamil 240 mg/day or verapamil 180 + trandolapril 2 mg/day combination; forced double-dose titration was carried out at the 4th week. Treatment duration was 6 months.

Outcome measures: Changes in BP, 24 h proteinuria, serum albumin and calcium.

Results: BP was significantly reduced with the four treatments [SBP/DBP (mmHg]: atenolol 12.2/9.9; trandolapril 12.9/9.3; verapamil 8.2/7.9 and verapamil + trandolapril 13.6/11.3) without differences between them. A significant fall in proteinuria was seen in the trandolapril, 40.2% [95% confidence interval (CI) 24.3-56.2%], and verapamil + trandolapril groups, 48.5% (95% CI, 31.7-64.3%) accompanied with increases in serum albumin (trandolapril: from 3.86 +/- 0.64 to 4.03 +/- 0.67 g/dl; verapamil + trandolapril: from 4.15 +/- 0.58 to 4.40 +/- 0.51 g/dl).

Conclusions: In patients with proteinuric primary renal disease, adequate dose titration of antihypertensive drugs may provide a substantial BP reduction. Only angiotensin-converting enzyme inhibitor (trandolapril) treatment, alone or better combined with verapamil, reduces proteinuria and increases serum albumin.