title: Renoprotective efficacy of valsartan in chronic non-diabetic proteinuric nephropathies with renin-angiotensin system gene polymorphisms.
abstract: OBJECTIVE
  The renoprotective effects of angiotensin receptor blockers vary considerably among individuals. We investigated the renoprotective effects of valsartan according to polymorphisms of the renin-angiotensin system and transforming growth factor-b1 (TGFB1) genes in patients with chronic non-diabetic proteinuric nephropathies.
  
  
  METHODS
  Two hundred and thirty-nine non-diabetic patients with proteinuria of at least 1 g/day were enrolled. Patients received 80 g of valsartan daily, followed by 160 mg/day after 6 weeks. The follow-up period was 18 months. The status of the angiotensin-converting enzyme (ACE) insertion/deletion, angiotensinogen (AGT) M235T, type 1 angiotensin II receptor (ATR1) A1166C, and TGFB1 C509 and T869C polymorphisms was determined in 162 patients.
  
  
  RESULTS
  Valsartan treatment caused a significant reduction in proteinuria from baseline throughout the study in patients with each genotype of the ACE, AGT and TGFB1 genes. However, patients with the ATR1 AC genotype had no significant reduction in proteinuria from baseline throughout the study course. The median reductions in proteinuria after 6 months were 45.7% and 10.8% in the patients with the ATR1 AA and AC genotypes, respectively (P = 0.034). The annual change in the estimated glomerular filtration rate did not differ significantly among the genotypes for each gene. On multiple regression analysis, the change in proteinuria after 6 months of treatment was independently associated with the ATR1 genotype and the change in blood pressure (P = 0.005 and 0.019, respectively).
  
  
  CONCLUSIONS
  Valsartan treatment significantly reduced the blood pressure and urinary protein excretion of patients with chronic non-diabetic proteinuric nephropathies. Interindividual differences in the anti-proteinuric effect of valsartan may be related partly to the ATR1 A1166C polymorphism.
authors.affiliation: Department of Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Korea.
authors.forename: Yu-Ji
authors.initials: YJ
authors.lastname: Lee
authors.forename: Hye Ryoun
authors.initials: HR
authors.lastname: Jang
authors.forename: Seong Gyun
authors.initials: SG
authors.lastname: Kim
authors.forename: Dong-Wan
authors.initials: DW
authors.lastname: Chae
authors.forename: Jun-Young
authors.initials: JY
authors.lastname: Do
authors.forename: Jung Eun
authors.initials: JE
authors.lastname: Lee
authors.forename: Wooseong
authors.initials: W
authors.lastname: Huh
authors.forename: Dae Joong
authors.initials: DJ
authors.lastname: Kim
authors.forename: Ha Young
authors.initials: HY
authors.lastname: Oh
authors.forename: Yoon-Goo
authors.initials: YG
authors.lastname: Kim
mesh_terms: D000328:Adult; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000808:Angiotensinogen / Q000235:genetics; D002908:Chronic Disease; D005260:Female; D005838:Genotype; D006801:Humans; D007668:Kidney / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D020011:Protective Agents / Q000494:pharmacology; D011507:Proteinuria / Q000188:drug therapy* / Q000235:genetics; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics; D012084:Renin-Angiotensin System / Q000235:genetics*; D013777:Tetrazoles / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1 / Q000235:genetics; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000068756:Valsartan
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D020011:Protective Agents; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; D053773:Transforming Growth Factor beta1; D000808:Angiotensinogen; D000068756:Valsartan; D007703:Peptidyl-Dipeptidase A; D014633:Valine