Effects of Spironolactone in Dialysis

Summary

Several studies indicate that chronic kidney disease patients give a high cardiovascular risk and have an intrinsic relationship with hypertension and cardiomyopathy: characterized by left ventricular hypertrophy and interstitial fibrosis. The reversal of left ventricular hypertrophy is associated with increased life expectancy in these patients. The renin angiotensin aldosterone system plays an important role in blood pressure control. Even patients using converting enzyme inhibitors inhibitors or angiotensin II blockers may experience the so called aldosterone breakthrough phenomenon (inappropriately called aldosterone escape). This phenomenon is documented in patients with heart disease and in chronic kidney disease. Spironolactone is a synthetic steroid that acts as an antagonist of aldosterone, which has historically avoided in chronic kidney disease patients, given the risk of hyperkalemia. However, its active metabolite, canrenone and spironolactone, are able to antagonize the binding of ouabain, a Na+/K+ATPase inhibitor, to its receptor. The Na+/K+-ATPase inhibition results in changes in sodium gradients, and increases the calcium influx through the transporter Na+/Ca+ in specific regions of the membrane. Spironolactone and canrenone in previous research were able to reverse left ventricular hypertrophy in chronic kidney disease patients on conservative treatment, which turn this drug and its metabolite potential tools for reversion of left ventricular hypertrophy in chronic kidney disease. The aim of this study is to verify the safety, tolerability and efficacy in the reversal of target organ damage from the use of spironolactone added to conventional antihypertensive therapy in chronic kidney disease patients on hemodialysis, in addition to measuring its ability to reduce left ventricular hypertrophy and arterial stiffness indices. Interventional randomized, double-blind, placebo-controlled study comprising two groups: one that will take 25mg of spironolactone associated with conventional antihypertensive therapy and another that will take spironolactone placebo associated with conventional antihypertensive therapy. Each group will consist of 30 patients. Clinical and laboratory investigations, as well as home monitoring of blood pressure, echocardiography, determination of pulse wave velocity, augmentation index, and central blood pressure measurement of serum aldosterone will be are evaluated before and after treatment that will last 12 months.

Timeline

Start

2011-03

Primary completion

2012-12

Completion

2013-12

Publications

• Hasegawa T, Nishiwaki H, Ota E, Levack WM, Noma H. Aldosterone antagonists for people with chronic kidney disease requiring dialysis. Cochrane Database Syst Rev. 2021 Feb 15;2(2):CD013109. doi: 10.1002/14651858.CD013109.pub2.
• Feniman De Stefano GM, Zanati-Basan SG, De Stefano LM, Silva VR, Xavier PS, Barretti P, da Silva Franco RJ, Caramori JC, Martin LC. Aldosterone is associated with left ventricular hypertrophy in hemodialysis patients. Ther Adv Cardiovasc Dis. 2016 Oct;10(5):304-13. doi: 10.1177/1753944716644583. Epub 2016 Apr 27.
• Feniman-De-Stefano GM, Zanati-Basan SG, De Stefano LM, Xavier PS, Castro AD, Caramori JC, Barretti P, Franco RJ, Martin LC. Spironolactone is secure and reduces left ventricular hypertrophy in hemodialysis patients. Ther Adv Cardiovasc Dis. 2015 Aug;9(4):158-67. doi: 10.1177/1753944715591448. Epub 2015 Jun 26.

Drugs

Indications