ANGIOTENSIN-CONVERTING ENZYME GENE POLYMORPHISM DETERMINES THE ANTIPROTEINURIC AND SYSTEMIC HEMODYNAMIC-EFFECT OF ENALAPRIL IN PATIENTS WITH PROTEINURIC RENAL-DISEASE

Angiotensin-converting enzyme (ACE) inhibitors are known to reduce blo od pressure and proteinuria in a variety of different glomerular disea ses. Nonetheless, a marked interindividual difference in the efficacy of these agents exists. The activity of the ACE and therefore of the r enin-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 shows to exhibit higher activity of plasmati c ACE when compared to patients with the insertion genotype. We theref ore studied prospectively the hemodynamic and antiproteinuric effect o f a 6-month therapy with enalapril in patients with biopsy-proven prot einuric glomerular diseases and the DD (n = 10) and ID/II (n = 26) gen otype. Although patients with the DD genotype received a slightly high er dose of enalapril, blood pressure and proteinuria did not change si gnificantly. However, both were significantly reduced in the II/ID gro up after 10 weeks and 6 months of therapy. Creatinine clearance decrea sed steadily in DD patients. In II/ID patients, creatinine clearance w as 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 ef fect of enalapril in patients with proteinuric glomerular disease.