Angiotensin-converting enzyme gene polymorphism determines the antiproteinuric and systemic hemodynamic effect of enalapril in patients with proteinuric renal disease. Austrian Study Group of the Effects of Enalapril Treatment in Proteinuric Renal Disease.
Angiotensin-converting enzyme (ACE) inhibitors are known to reduce blood pressure and proteinuria in a variety of different glomerular diseases. Nonetheless, a marked interindividual difference in the efficacy of these agents exists. The activity of the ACE and therefore of the renin-angiotensin-aldosterone system (RAAS) has been shown to be under genetic influence. Patients with a deletion genotype at the intron 16 of the ACE gene have been shown to exhibit higher activity of plasmatic ACE when compared to patients with the insertion genotype. We therefore studied prospectively the hemodynamic and antiproteinuric effect of a 6-month therapy with enalapril in patients with biopsy-proven proteinuric glomerular diseases and the DD (n = 10) and ID/II (n = 26) genotype. Although patients with the DD genotype received a slightly higher dose of enalapril, blood pressure and proteinuria did not change significantly. However, both were significantly reduced in the II/ID group after 10 weeks and 6 months of therapy. Creatinine clearance decreased steadily in DD patients. In II/ID patients, creatinine clearance was reduced significantly after 10 weeks of therapy but increased again thereafter and the value at 6 months was again comparable to the one obtained in the DD patients. We conclude from our study that the ACE genotype influences the blood pressure-lowering and antiproteinuric effect of enalapril in patients with proteinuric glomerular disease.
Haas
M
M
Department of Internal Medicine III, University of Vienna, Austria.
Yilmaz
N
N
Schmidt
A
A
Neyer
U
U
Arneitz
K
K
Stummvoll
H K
HK
Wallner
M
M
Auinger
M
M
Arias
I
I
Schneider
B
B
Mayer
G
G
D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D003404:Creatinine / Q000378:metabolism; D004247:DNA / Q000032:analysis; D004656:Enalapril / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000187:drug effects / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D011507:Proteinuria / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D012964:Sodium / Q000652:urine; D016896:Treatment Outcome
D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril; D004247:DNA; D012964:Sodium; D003404:Creatinine; D007703:Peptidyl-Dipeptidase A