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CLINICAL RESEARCH: CLINICAL TRIAL

Effect of Spironolactone on Left Ventricular Mass and Aortic Stiffness in Early-Stage Chronic Kidney Disease

A Randomized Controlled Trial

Nicola C. Edwards, BMBS^_*, Richard P. Steeds, MD^_*, Paul M. Stewart, PhD, Charles J. Ferro, MD and Jonathan N. Townend, MD^_*,_*

^_* Department of Cardiology, University Hospital Birmingham and University of Birmingham, Birmingham, United Kingdom
Department of Medicine, University Hospital Birmingham and University of Birmingham, Birmingham, United Kingdom
Department of Nephrology, University Hospital Birmingham and University of Birmingham, Birmingham, United Kingdom

Manuscript received October 26, 2008; revised manuscript received January 29, 2009, accepted March 3, 2009.

^_* Reprint requests and correspondence: Dr. Jonathan N. Townend, Department of Cardiovascular Medicine, University of Birmingham, Birmingham B15 2TH, United Kingdom (Email: john.townend{at}uhb.nhs.uk).

Objectives: We sought to determine whether the addition of spironolactone to angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) improves left ventricular mass and arterial stiffness in early-stage chronic kidney disease (CKD).

Background: Chronic kidney disease is associated with a high risk of cardiovascular disease and a high prevalence of left ventricular hypertrophy and arterial stiffness that confer an adverse prognosis. It is believed that these abnormalities are in part a result of activation of the renin-angiotensin-aldosterone system.

Methods: After an active run-in phase with spironolactone 25 mg once daily, 112 patients with stage 2 and 3 CKD with good blood pressure control (mean daytime ambulatory blood pressure <130/85 mm Hg) on established treatment with ACE inhibitors or ARBs were randomized to continue spironolactone or to receive a matching placebo. Left ventricular mass (cardiac magnetic resonance) and arterial stiffness (pulse wave velocity/analysis, aortic distensibility) were measured before run in and after 40 weeks of treatment.

Results: Compared with placebo, the use of spironolactone resulted in significant improvements in left ventricular mass (–14 ± 13 g vs. +3 ± 11 g, p < 0.01), pulse wave velocity (–0.8 ± 1.0 m/s vs. –0.1 ± 0.9 m/s, p < 0.01), augmentation index (–5.2 ± 6.1% vs. –1.4 ± 5.9%, p < 0.05), and aortic distensibility (0.69 ± 0.86 x 10^–3 mm Hg vs. 0.04 ± 1.04 x 10^–3 mm Hg, p < 0.01).

Conclusions: The use of spironolactone reduces left ventricular mass and improves arterial stiffness in early-stage CKD. These effects suggest that aldosterone exerts adverse cardiovascular effects in CKD and that spironolactone is worthy of further study as a treatment that could reduce adverse cardiovascular events. (Is Spironolactone Safe and Effective in the Treatment of Cardiovascular Disease in Mild Chronic Renal Failure; NCT00291720)

Key Words: chronic kidney disease • arterial stiffness • left ventricular mass • renin-angiotensin-aldosterone system • spironolactone

Abbreviations and Acronyms   ACE = angiotensin-converting enzyme   ARB = angiotensin receptor blocker   Aug = aortic augmentation pressure   Aug Ix = augmentation index   Aug Ix 75 = augmentation index corrected for a heart rate of 75 beats/min   CKD = chronic kidney disease   CMR = cardiovascular magnetic resonance   EDV = end-diastolic volume   eGFR = estimated glomerular filtration rate   GFR = glomerular filtration rate   hsCRP = high-sensitivity C-reactive protein   LV = left ventricle/ventricular   LVH = left ventricular hypertrophy   PAC = plasma aldosterone concentration   PWA = pulse-wave analysis   PWV = pulse-wave velocity   RV = right ventricle/ventricular

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