Angiotensin-Converting Enzyme Gene Polymorphism Determines the Antiproteinuric and Systemic Hemodynamic Effect of Enalapril in Patients with Proteinuric Renal Disease

Abstract

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.

Cost-effectiveness of ACE inhibitor therapy to prevent dialysis in nondiabetic nephropathy: influence of the ACE insertion/deletion polymorphism

“…In fact, several studies reported that the D allele is associated with ACEi therapy resistance [16,19], contrary to our model assumptions. The trial used for our analyses was the only trial evaluating a hard endpoint, namely ESRD.…”

“…ACE (I/D) polymorphism prevalences were derived from several clinical trials in nondiabetic nephropathy [10,11,[16][17][18][19][20], all described in a systematic review by Ruggenenti et al [9]. QoL estimates were obtained by examining a recently published systematic review [3], in which one study was reported with QoL estimates for CKD and ESRD based on community preferences, using the Health Utilities Index-3 [21].…”

Angiotensin Converting Enzyme Insertion/Deletion Polymorphism and Renoprotection in Diabetic and Nondiabetic Nephropathies

“…Consistently, a smaller study in patients with IgA nephropathy found more treatment-induced proteinuria reduction in those with the DD than in those with the ID or II genotype (55). Other studies that, compared with the REIN analysis, included remarkably smaller numbers of patients, had shorter follow-up and, in most cases, did not measure the GFR failed to find a correlation between ACE I/D polymorphism and response to ACE inhibitor treatment (56,57) or even showed a better outcome on ACE inhibitor therapy in carriers of the I allele (37,58). In addition to the limited statistical power of the above studies, a possible interpretation for these findings is that in those with the DD genotype the response to ACE inhibitors was blunted by an excessive dietary intake of sodium (57).…”

Long-Term Renoprotective Effects of Losartan in Diabetic Nephropathy

“…Reduced long-term renoprotective effect of ACE inhibition has been demonstrated in type 1 diabetic patients with diabetic nephropathy homozygous for the D allele (3). Furthermore, the ACE/ID polymorphism has been suggested to play an important role in the individual antiproteinuric response to ACE inhibition in diabetic renal disease (4,15), whereas conflicting results have been reported in nondiabetic renal disease (2,11,12,16,17).…”