• Katsuyuki Ando, Hiroshi Ohtsu, Shunya Uchida, Shinya Kaname, Yoshihiro Arakawa, Toshiro Fujita, and EVALUATE Study Group.
• The University of Tokyo, Tokyo, Japan.
• Lancet Diabetes Endocrinol. 2014 Dec 1; 2 (12): 944-53.

BackgroundRenin-angiotensin system inhibitors have renoprotective effects in patients with chronic kidney disease, but most patients treated with these drugs have residual urinary albumin excretion. Some small clinical studies show that mineralocorticoid receptor blockade reduces albuminuria. Our study aimed to examine the beneficial effects of addition of a selective aldosterone antagonist, eplerenone, to renin-angiotensin system inhibitors in hypertensive patients with non-diabetic chronic kidney disease.MethodsIn this double-blind, randomised, placebo-controlled trial, we enrolled hypertensive patients, aged 20–79 years, with albuminuria (urinary albumin-to-creatinine ratio [UACR] in the first morning void urine of 30–599 mg/g), an estimated glomerular filtration rate of 50 mL/min per 1·73 m2 or more, and who had received an angiotensin-converting enzyme inhibitor, an angiotensin receptor blocker, or both, for at least 8 weeks. Participants were from 59 clinics and hospitals in Japan. Eligible patients were randomly assigned (1:1), stratified by baseline characteristics, to either low-dose eplerenone (50 mg/day) or placebo, with continuation of standard antihypertensive treatment to attain therapeutic goals (<130/80 mm Hg) for 52 weeks. We assessed efficacy in all patients who received allocated treatment, provided a baseline and post-treatment urine sample, and remained in follow-up. We assessed safety in all patients who received allocated treatment. The primary efficacy measure was percent change in UACR in the first morning void urine at week 52 from baseline. The trial is registered at the clinical trials registry of University Hospital Medical Information Network (UMIN), trial identification number UMIN000001803.FindingsBetween April 1, 2009, and March 31, 2012, we randomly allocated 170 patients to the eplerenone group and 166 patients to the placebo group. In the primary efficacy analysis, mean percent change in UACR from baseline was −17·3% (95% CI −33·65 to −0·94) for 158 patients in the eplerenone group compared with 10·3% (−6·75 to 22·3) for 146 patients in the placebo group (absolute difference −27·6% [–51·15 to −3·96]; p=0·0222). In the safety analyses, 53 (31%) of 169 patients in the eplerenone group had adverse events (five serious), as did 49 (30%) of 163 in the placebo group (seven serious). Although mean serum potassium concentration was higher in the eplerenone group than the placebo group, severe hyperkalaemia (>5·5 mmol/L) was not recorded in either group.InterpretationAddition of low-dose eplerenone to renin-angiotensin system inhibitors might have renoprotective effects through reduction of albuminuria in hypertensive patients with non-diabetic chronic kidney disease, without serious safety concerns.FundingPfizer.

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