Effect of spironolactone on left ventricular mass and aortic stiffness in early-stage chronic kidney disease: a randomized controlled trial.
OBJECTIVE
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).
Edwards
Nicola C
NC
Department of Cardiology, University Hospital Birmingham and University of Birmingham, Birmingham, UK.
Steeds
Richard P
RP
Stewart
Paul M
PM
Ferro
Charles J
CJ
Townend
Jonathan N
JN
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage; D001011:Aorta / Q000187:drug effects* / Q000473:pathology; D004359:Drug Therapy, Combination; D005260:Female; D006352:Heart Ventricles / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy* / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000008:administration & dosage*; D009929:Organ Size; D012084:Renin-Angiotensin System / Q000187:drug effects; D012720:Severity of Illness Index; D013148:Spironolactone / Q000008:administration & dosage*; D016896:Treatment Outcome
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone