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- W1905682640 abstract "Objective: Excessive salt intake was reported to counteract the renoprotective effect by the blockade of renin-angiotensin system (RAS) on chronic kidney disease (CKD) of hypertensive patients. We have shown salt loading induces hypertension and renal damage via the ligand-independent activation of mineralocorticoid receptor (MR) through Rac1 activation in rodent kidneys (Nat Med 2008, J Clin Invest 2011). Therefore, we hypothesized that excessive salt intake activates Rac1-MR pathway also in the hypertensive patients, leading to the progression of CKD, despite of RAS blockade. To examine the hypothesis, we analyzed the participants of EVALUATE study, a double-blind, randomised, placebo-controlled trial that enrolled non-diabetic hypertensive patients with albuminuria, in which all participants were received the aldosterone blocker eplerenone or placebo depending on random assignment in addition to RAS blockade (Lancet Diabetes Endocrinol 2014). Design and method: We analyzed 314 subjects who completed the study. They were divided into tertiles according to the estimated 24-h urinary sodium excretion at baseline (LOW / MIDDLE / HIGH) and evaluated the change in urinary albumin-to-creatinine ratio (UACR) from baseline. Results: UACR and blood pressure (BP) were not significantly different among groups at baseline. The percent change in UACR were as follows: LOW: −0.84% vs. −10.2%, MIDDLE: +9.5% vs. −19.5%, HIGH: +21.8% vs. −22.5%, placebo vs. eplerenone, respectively. Eplerenone effectively suppressed albuminuria only in HIGH. The decrease in systolic BP with eplerenone was also greater in the HIGH than in the LOW. Conclusions: Our result suggests that resistance to RAS blockade by excessive salt intake would be due to ligand-independent activation of MR. The antihypertensive effects of eplerenone is BP-dependent and independent. Eplerenone added on RAS blockade will be beneficial to treat CKD of hypertensive patients with excessive salt intake." @default.
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- W1905682640 date "2015-06-01" @default.
- W1905682640 modified "2023-10-18" @default.
- W1905682640 title "LB01.04" @default.
- W1905682640 doi "https://doi.org/10.1097/01.hjh.0000467466.62128.32" @default.
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