High dose Losartan and ACE gene polymorphism in IgA nephritis

Abstract

Background/aims Several studies have reported varying results of the influence of ACE gene on ACEI/ ARB therapy. The efficacy of high dose ARB and its influence on ACE gene have not been explored. This is a 6 year randomised trial in IgA nephritis comparing high dose ARB (Losartan 200 mg/day) with normal dose ARB (Losartan 100 mg/day), normal dose ACEI (20 mg/day) and low dose ACEI (10 mg/day). Results Patients on high dose ARB had significantly lower proteinuria, 1.0 ± 0.8 gm/day compared to 1.7 ± 1.0 g/day in the other groups (P = 0.0005). The loss in eGFR was 0.7 ml min -1 year -1 for high dose ARB compared to 3.2-3.5 ml min -1 year -1 for the other three groups (P = 0.0005). There were more patients on high dose ARB with improvement in eGFR compared to other three groups (P \ 0.001). Comparing patients with the three ACE genotypes DD, ID and II, all three groups responded well to therapy with decrease in proteinuria (P \ 0.002). Only those on low dose ACEI (10 mg/day) with the I allele had increased in ESRF (P = 0.037). Conclusion High dose ARB is more efficacious in reducing proteinuria and preserving renal function when compared with normal dose ARB and ACEI, and also obviates the genomic influence of ACE gene polymorphism on renal survival.

The Tissue Renin-Angiotensin System and Its Role in the Pathogenesis of Major Human Diseases: Quo Vadis?

“…Various RAS inhibitors were shown to have anti-inflammatory and anabolic effects in degenerative and inflammatory diseases [ 76 , 78 , 79 , 80 , 107 , 185 , 186 , 187 , 188 , 189 , 190 , 191 , 192 ]. As described previously, it is not possible to distinguish the systemic effects of RAS inhibitors when evaluating tRAS response to these inhibitors in vivo.…”

The potential therapeutic use of renin–angiotensin system inhibitors in the treatment of inflammatory diseases

“…A 6‐year randomized trial in IgA nephritis showed that high dose losartan (200 mg/day) was more efficacious in reducing proteinuria as well as preserving renal function when compared with normal dose losartan (100 mg/day) and enalapril (20 mg/day; Woo et al, ). In a randomized controlled trial conducted by Qiu et al (), irbesartan significantly reduced proteinuria in 479 patients with primary chronic glomerulonephritis.…”

A Physiologic Approach to the Pharmacogenomics of Hypertension

“…These endpoints have ranged from improvement in measured hemodynamics to reduction in proteinuria to BP response. However, significant conflicting data have since been reported that reveal no association between rs1799752 and ACEI or ARB BP response 17,[33][34][35][36][37][38][39] . Although evidence does not support the use of rs1799752 as a predictor of ACEI or ARB response, a few studies suggest this SNP may remain a predictor of diuretic response [40][41][42] .…”