Abstract
BackgroundPatients with chronic kidney disease (CKD) have high cardiovascular mortality and morbidity associated with increased arterial stiffness. Plasma aldosterone levels are increased in CKD, and aldosterone has been found to increase vascular inflammation and fibrosis. It was hypothesized that aldosterone receptor inhibition with eplerenone could reduce arterial stiffness in CKD stage 3–4.Study DesignThe design was randomized, open, parallel group. Measurements of arterial stiffness markers were undertaken at weeks 1 and 24.Intervention24 weeks of add-on treatment with 25–50 mg eplerenone or standard medication.OutcomesPrimary outcome parameter was carotid-femoral pulse wave velocity (cfPWV). Secondary outcomes were augmentation index (AIx), ambulatory arterial stiffness index (AASI) and urinary albumin excretion.ResultsFifty-four CKD patients (mean eGFR 36 mL/min/1.73 m2, SD 11) were randomized. Forty-six patients completed the trial. The mean difference in cfPWV changes between groups was 0.1 m/s (95%CI: −1.0, 1.3), P = 0.8. The mean difference in AIx changes between groups was 4.4% (0.1, 8.6), P = 0.04. AASI was unchanged in both groups. The ratio of change in urinary albumin excretion in the eplerenone group compared to the control was 0.61 (0.37, 1.01), P = 0.05. Four patients were withdrawn from the eplerenone group including three because of possible side effects; one was withdrawn from the control group. Mild hyperkalemia was seen on three occasions and was easily managed.LimitationsThe full planned number of patients was not attained. The duration of the trial may have been too short to obtain full effect of eplerenone on the arteries.ConclusionsAdd-on treatment with eplerenone in CKD stage 3–4 did not significantly reduce cfPWV. There may be beneficial vascular effects leading to attenuated pulse wave reflection. Treatment was well-tolerated.Trial Registration ClinicalTrials.gov NCT01100203
Highlights
Arterial stiffness is increased in patients with chronic kidney disease (CKD) compared to the background population [1]
There may be beneficial vascular effects leading to attenuated pulse wave reflection
In rats supplied with aldosterone and salt, attenuation of aortic stiffness was reported after treatment with the selective aldosterone receptor blocker eplerenone [18]
Summary
Arterial stiffness is increased in patients with chronic kidney disease (CKD) compared to the background population [1]. This adds to the increased burden of cardiovascular morbidity and mortality in CKD. Markers of arterial stiffness have been found to be independent predictors of all-cause and cardiovascular mortality in patients with CKD and hypertension as well as in the general population [3,4,5,6,7,8,9,10]. A recent study in patients with CKD stage 2–3 reported a decrease of arterial stiffness after treatment with spironolactone, a non-selective aldosterone inhibitor added on to RAS-blockade and compared to placebo [21]. Patients with chronic kidney disease (CKD) have high cardiovascular mortality and morbidity associated with increased arterial stiffness. It was hypothesized that aldosterone receptor inhibition with eplerenone could reduce arterial stiffness in CKD stage 3–4
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