Antiproteinuric effect of losartan in non-diabetic renal disease is not dependent on ACE insertion/deletion polymorphism.
BACKGROUND
The antiproteinuric effect of angiotensin-converting enzyme (ACE) inhibitors appears to vary depending on the ACE insertion (I)/deletion (D) genotype in non-diabetic nephropathy. This interaction may be overcome by using an angiotensin II receptor blocker. We evaluated the short-term antiproteinuric effect of losartan according to the ACE I/D genotype in patients with non-diabetic proteinuric renal diseases.


METHODS
Ninety-nine (II/ID/DD: 36/52/11) non-diabetic patients with overt proteinuria were enrolled. The patients received losartan 50 mg daily followed by 100 mg in two treatment periods each lasting 12 weeks. Clinical parameters including proteinuria were measured at baseline and at the end of each period.


RESULTS
At baseline each genotype (II/ID/DD) had comparable mean arterial blood pressure (mean +/- SD) 103.2 +/- 11.1/102.7 +/- 10.6/104.1 +/- 15.3; proteinuria (geometric mean, 95% CI, mg/day) 1,839 (1,518-2,227)/1,998 (1,683-2,372)/1,613 (1,072-2,427), and creatinine clearance (ml/min/1.73 m(2)) 65.7 +/- 28.4/63.2 +/- 27.8/68.8 +/- 25.3, respectively. Both doses of losartan significantly lowered blood pressure and proteinuria (p < 0.05 vs. baseline), and losartan 100 mg was more effective than 50 mg in reducing proteinuria (52.5 +/- 29.0 vs. 40.5 +/- 30.8%, respectively, p = 0.001). No differences in the antiproteinuric effect of losartan was observed among the ACE I/D genotype. Losartan 100 mg demonstrated a comparable degree of mean arterial pressure (mean +/- SD, %) (II/ID/DD, 13.3 +/- 7.6/10.8 +/- 9.8/13.0 +/- 11.6, respectively, p = NS) and proteinuria reduction (mean, 95% CI) among the three genotypes (51.4% (40.3-62.5%)/53.4% (45.5-61.4%)/51.4% (40.0-63.8%), respectively, p = NS).


CONCLUSIONS
Our data suggest that losartan provides a similar short-term antiproteinuric response for all three genotypes of ACE I/D genotype in non-diabetic proteinuric chronic renal disease.
Park
Hyeong Cheon
HC
Department of Internal Medicine, College of Medicine, Institute of Kidney Disease, Yonsei University, Seoul, Korea.
Choi
Hoon Young
HY
Kim
Beom Seok
BS
Kang
Shin Wook
SW
Choi
Kyu Hun
KH
Ha
Sung Kyu
SK
Lee
Ho Yung
HY
Han
Dae Suk
DS
D000328:Adult; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects; D004232:Diuretics / Q000008:administration & dosage; D004359:Drug Therapy, Combination; D005260:Female; D017353:Gene Deletion; D005838:Genotype; D006801:Humans; D019808:Losartan / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic; D015995:Prevalence; D011507:Proteinuria / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics*; D016896:Treatment Outcome
D047228:Angiotensin II Type 1 Receptor Blockers; D004232:Diuretics; D007703:Peptidyl-Dipeptidase A; D019808:Losartan