Eplerenone attenuates pulse wave reflection in chronic kidney disease stage 3-4--a randomized controlled study

PLoS One. 2013 May 21;8(5):e64549. doi: 10.1371/journal.pone.0064549. Print 2013.

Abstract

Background: Patients 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 design: The design was randomized, open, parallel group. Measurements of arterial stiffness markers were undertaken at weeks 1 and 24.

Intervention: 24 weeks of add-on treatment with 25-50 mg eplerenone or standard medication.

Outcomes: Primary outcome parameter was carotid-femoral pulse wave velocity (cfPWV). Secondary outcomes were augmentation index (AIx), ambulatory arterial stiffness index (AASI) and urinary albumin excretion.

Results: Fifty-four CKD patients (mean eGFR 36 mL/min/1.73 m(2), 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 Four patients were withdrawn from the eplerenone group including three because of possible side effects; one was withdrawn from the control group.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.

Limitations: The 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.

Conclusions: Add-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.govNCT01100203.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Pressure / drug effects
  • Demography
  • Eplerenone
  • Female
  • Heart Rate / drug effects
  • Humans
  • Male
  • Middle Aged
  • Mineralocorticoid Receptor Antagonists / adverse effects
  • Mineralocorticoid Receptor Antagonists / pharmacology
  • Mineralocorticoid Receptor Antagonists / therapeutic use
  • Pulse Wave Analysis*
  • Renal Insufficiency, Chronic / blood
  • Renal Insufficiency, Chronic / drug therapy*
  • Renal Insufficiency, Chronic / physiopathology*
  • Renal Insufficiency, Chronic / urine
  • Spironolactone / adverse effects
  • Spironolactone / analogs & derivatives*
  • Spironolactone / therapeutic use
  • Vascular Stiffness / drug effects

Substances

  • Mineralocorticoid Receptor Antagonists
  • Spironolactone
  • Eplerenone

Associated data

  • ClinicalTrials.gov/NCT01100203

Grants and funding

LB was the recipient of a research fellowship grant from the Danish Cardiovascular Research Academy. The work was further made possible by contributions from the following foundations: the Danish Kidney Association, the Danish Kidney Association in Viborg, the Danish Society of Nephrology, the Research Council of Copenhagen University Hospital Herlev, The Gangsted Foundation, and the foundations of Sophus and Astrid Jacobsen, Sigurd and Addie Abrahamson , Aase Bay, Jacob and Olga Madsen, Eva and Robert Voss Hansen, and Helen and Ejnar Bjørnow. The SphygmoCor® apparatus was donated by the foundations of L. F. Foght and Frode V. Nyegaard and Toyota-Fonden, Denmark. Study medication was provided by the Department of Nephrology, Herlev Hospital. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.