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Effect of spironolactone on left ventricular systolic and diastolic function in patients with early stage chronic kidney disease.

Author(s): Edwards NC, Ferro CJ, Kirkwood H, Chue CD, Young AA, Stewart PM, Steeds RP, Townend JN

Affiliation(s): Department of Cardiology, University Hospital Birmingham and University of Birmingham, Birmingham, United Kingdom. n.c.edwards@bham.ac.uk

Publication date & source: 2010-11-15, Am J Cardiol., 106(10):1505-11.

Publication type: Randomized Controlled Trial; Research Support, Non-U.S. Gov't

Patients with early chronic kidney disease (CKD) have an increased risk for cardiovascular disease. Aldosterone levels are elevated and might impair ventricular function through adverse myocardial and vascular proinflammatory and fibrotic effects. In the Chronic Renal Impairment in Birmingham II (CRIB II) study, it was hypothesized that mineralocorticoid receptor blockade with spironolactone in addition to angiotensin-converting enzyme inhibitors or angiotensin receptor blockers would improve left ventricular (LV) function and markers of inflammation, ventricular stretch, and collagen turnover in early CKD. A total of 112 patients with early CKD were randomized to spironolactone 25 mg/day or placebo for 40 weeks. Ventricular function was assessed by echocardiography and cardiac magnetic resonance imaging tagging. High-sensitivity C-reactive protein, N-terminal-pro-B-type natriuretic peptide, and aminoterminal propeptide of type III procollagen were measured. Spironolactone improved LV long-axis systolic function (Sm 8.2 +/- 1.4 vs 7.7 +/- 1.3 cm/s, p <0.05), torsion (7.77 +/- 1.61 degrees vs 6.77 +/- 1.48 degrees , p <0.05), and myocardial deformation (strain rate -1.14 +/- 0.24 vs -1.09 +/- 0.20 s(-1), p <0.05) compared to placebo, without a change in the ejection fraction. Markers of LV relaxation (E/e' ratio 7.2 +/- 2.3 vs 8.5 +/- 2.3, p <0.05) and suction (M-mode propagation velocity 56 +/- 12 vs 50 +/- 12 cm/s, p <0.05) were also improved. Spironolactone reduced N-terminal-pro-B-type natriuretic peptide (24.8 pmol/L [range 0.4 to 122.4] vs 39.4 pmol/L [range 10.8 to 102.4], p <0.01) and attenuated an increase in aminoterminal propeptide of type III procollagen observed with placebo. In conclusion, spironolactone improves markers of regional LV systolic and diastolic function in early CKD. Copyright (c) 2010 Elsevier Inc. All rights reserved.

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