Blood-pressure control for renoprotection in patients with non-diabetic chronic renal disease (REIN-2): multicentre, randomised controlled trial

Lancet. 2005 Mar 12-18;365(9463):939-46. doi: 10.1016/S0140-6736(05)71082-5.


Background: In chronic nephropathies, inhibition of angiotensin-converting enzyme (ACE) is renoprotective, but can further renoprotection be achieved by reduction of blood pressure to lower than usual targets? We aimed to assess the effect of intensified versus conventional blood-pressure control on progression to end-stage renal disease.

Methods: We undertook a multicentre, randomised controlled trial of patients with non-diabetic proteinuric nephropathies receiving background treatment with the ACE inhibitor ramipril (2.5-5 mg/day). We randomly assigned participants either conventional (diastolic <90 mm Hg; n=169) or intensified (systolic/diastolic <130/80 mm Hg; n=169) blood-pressure control. To achieve the intensified blood-pressure level, patients received add-on therapy with the dihydropyridine calcium-channel blocker felodipine (5-10 mg/day). The primary outcome measure was time to end-stage renal disease over 36 months' follow-up, and analysis was by intention to treat.

Findings: Of 338 patients who were randomised, three (two assigned intensified and one allocated conventional blood-pressure control) never took study drugs and they were excluded. Over a median follow-up of 19 months (IQR 12-35), 38/167 (23%) patients assigned to intensified blood-pressure control and 34/168 (20%) allocated conventional control progressed to end-stage renal disease (hazard ratio 1.00 [95% CI 0.61-1.64]; p=0.99).

Interpretation: In patients with non-diabetic proteinuric nephropathies receiving background ACE-inhibitor therapy, no additional benefit from further blood-pressure reduction by felodipine could be shown.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Angiotensin-Converting Enzyme Inhibitors / administration & dosage
  • Antihypertensive Agents / administration & dosage*
  • Blood Pressure* / drug effects
  • Calcium Channel Blockers / administration & dosage
  • Disease Progression
  • Drug Therapy, Combination
  • Felodipine / administration & dosage*
  • Female
  • Glomerular Filtration Rate
  • Humans
  • Kidney Diseases / complications
  • Kidney Diseases / drug therapy
  • Kidney Diseases / physiopathology*
  • Kidney Diseases / urine
  • Kidney Failure, Chronic / prevention & control
  • Male
  • Middle Aged
  • Proteinuria / complications
  • Ramipril / administration & dosage


  • Angiotensin-Converting Enzyme Inhibitors
  • Antihypertensive Agents
  • Calcium Channel Blockers
  • Ramipril
  • Felodipine