Effects of spironolactone in addition to conventional pharmacotherapy in dialysis patients

• Grant number: 10/10439-1
• Support Opportunities: Regular Research Grants
• Start date: December 01, 2010
• End date: November 30, 2013
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Luis Cuadrado Martin
• Grantee: Luis Cuadrado Martin
• Host Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Associated researchers: Beatriz Bojikian Matsubara ; Greicy Mara Mengue Feniman de Stefano ; Pasqual Barretti ; Roberto Jorge da Silva Franco

Abstract

Several studies indicate that Chronic Kidney Disease (CKD) patients give a high cardiovascular risk. The CKD has an intrinsic relationship with hypertension and cardiomyopathy that is characterized by left ventricular hypertrophy (LVH) and interstitial fibrosis, important predictors of cardiovascular mortality in CKD. Moreover, reversal of LVH is associated with increased life expectancy in these patients. The renin-angiotensin-aldosterone system (RAAS) plays an important role in blood pressure control. Even patients using ACE 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, as well as in CKD. Spironolactone is a synthetic steroid that acts as an antagonist of aldosterone, which has historically avoided in CKD 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. The increased influx of Ca+ and consequent contraction of vascular smooth muscle cell are crucial to the resulting increase in total peripheral vascular resistance and consequent increase in blood pressure as well as the processes of vascular and ventricular hypertrophy. Spironolactone and canrenone in previous research were able to reverse LVH in CKD patients on conservative treatment, which turn this drug and its metabolite potential tools for reversion of LVH in CKD. 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 CKD patients on hemodialysis, in addition to measuring its ability to reduce LVH and arterial stiffness indices. Design: interventional unicenter randomized, double-blind, placebo-controlled study comprising two groups: one that will take 12.5 mg to 25 mg of spironolactone associated with conventional antihypertensive therapy and another that will take spironolactone placebo 12,5 mg to 25 mg 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. (AU)