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

The PROCOPA Study Group

Journal of Hypertension:
Original papers: Kidney

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 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.

Author Information

*See appendix.

Sponsorship: This study was supported by a grant of Laboratorios Knoll, Spain.

Correspondence to Luis M. Ruilope, Hypertension Unit. Hospital 12 de Octubre, 28041 Madrid, Spain. Requests for reprints to Raúl Fernández, Laboratorios Knoll. Avda. de Burgos 91, 28050 Madrid, Spain. Tel:+34 913908284; fax:+34 915765644; email:

Received 6 March 2001

Revised 6 November 2001

Accepted 13 December 2001

© 2002 Lippincott Williams & Wilkins, Inc.