Abstract 2218: Effect of Spironolactone on Left Ventricular Mass and Aortic Stiffness in Early Stage Chronic Kidney Disease
Introduction Early stage chronic kidney disease (CKD) is a common condition affecting approximately 14% of the population. It is associated with major abnormalities of cardiovascular structure and function and carries a high risk of adverse cardiovascular events. Despite this, there is little available evidence to guide risk reducing treatment. Spironolactone reduces blood pressure and inhibits the direct adverse cardiovascular actions of aldosterone but its effects have not been examined in CKD.
Methods Following an active 4 week run in phase consisting of treatment with spironolactone 25 mg once daily, 112 patients with stage 2 and 3 CKD, no history of symptomatic cardiovascular disease or diabetes with controlled blood pressure (<130/80mmHg) on established treatment with ACE inhibitors and or Angiotensin Receptor Blockers (ARBs) were randomized to continue this treatment or receive a matching placebo for a further 36 weeks. Serum potassium was monitored frequently. Left ventricular mass (cardiac magnetic resonance, CMR) and arterial stiffness (pulse wave velocity, pulse wave analysis by applanation tonometry and aortic distensibility by CMR) were measured at baseline (before run-in) and after 40 weeks of treatment.
Results Spironolactone resulted in significant improvements in LV mass (−14g ± 13 vs. +3g ± 11, p<0.001), 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 x10−3 mmHg vs. 0.04 ± 1.04 x10−3 mmHg, p<0.001) compared to placebo. Systolic blood pressure was reduced with spironolactone (−11 ± 12mmHg vs. −5 ± 14mmHg, p<0.05). The changes in LV mass and parameters of arterial stiffness remained significantly different from placebo after correction for the change in blood pressure. The rate of hyperkalaemia was <1%.
Conclusion These data suggest that spironolactone reduces LV mass and improves vascular function as assessed by arterial stiffness in early stage CKD. The improvement in these prognostic markers suggests that spironolactone may be reduce cardiovascular risk in already optimally treated CKD patients and provides support for performing a clinical outcome trial.