Association between angiotensin-converting-enzyme gene polymorphism and failure of renoprotective therapy

Lancet. 1996 Jan 13;347(8994):94-5. doi: 10.1016/s0140-6736(96)90213-5.


Background: Polymorphism in the gene for angiotensin-converting enzyme (ACE), especially the DD genotype, is associated with risk for cardiovascular disease. Glomerulosclerosis has similarities to atherosclerosis, and we looked at ACE gene polymorphism in patients with kidney disease who were in a trial of long-term therapy with an ACE inhibitor or a beta-blocker.

Methods: 81 patients with non-diabetic renal disease had been entered into a randomised comparison of oral atenolol or enalapril to prevent progressive decline in renal function. The dose was titrated to a goal diastolic blood pressure of 10 mm Hg below baseline and/or below 95 mm Hg. The mean (SE) age was 50 (1) years, and the group included 49 men. Their renal function had been monitored over 3-4 years. We have looked at their ACE genotype, which we assessed with PCR.

Findings: 27 patients had the II genotype, 37 were ID, and 17 were DD. 11 patients were lost to follow-up over 1-3 years. The decline of glomerular filtration rate over the years was significantly steeper in the DD group than in the ID and the II groups (p = 0.02; means -3.79, -1.37, and -1.12 mL/min per year, respectively). The DD patients treated with enalapril fared as equally a bad course as the DD patients treated with atenolol. Neither drug lowered the degree of proteinuria in the DD group.

Interpretation: Our data show that patients with the DD genotype are resistant to commonly advocated renoprotective therapy.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adrenergic beta-Antagonists / therapeutic use*
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Atenolol / therapeutic use*
  • Double-Blind Method
  • Enalapril / therapeutic use*
  • Female
  • Genotype
  • Glomerular Filtration Rate / drug effects
  • Humans
  • Kidney Diseases / prevention & control*
  • Male
  • Middle Aged
  • Peptidyl-Dipeptidase A / genetics*
  • Polymorphism, Genetic*


  • Adrenergic beta-Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Atenolol
  • Enalapril
  • Peptidyl-Dipeptidase A