Renoprotective efficacy of valsartan in chronic non-diabetic proteinuric nephropathies with renin-angiotensin system gene polymorphisms

Aim: 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 mg 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). Conclusion: 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. In this study, the authors administrated valsartan to non-diabetic chronic kidney disease patients with urinary protein more than 1 g/day for 18 months. They observed that urinary protein was significantly reduced. On the relationship with gene polymorphism, patients with the ATR1 AC genotype had no significant reduction in proteinuria. However, other gene polymorphisms such as ACE, AGT and TGFB1 genes had no effect on reduction in proteinuria.