REN and heart failure: In CKD, in addition to up-regulation of the renin-angiotensin-aldosterone system (RAAS), sympathetic hyperactivation causes desensitization of cardiac beta-adrenergic receptors; furthermore, catecholamine clearance is reduced, resulting in a self-deteriorating cycle that worsens the GFR itself, and a progression of heart failure [27,28].The direct effects of sympathetic hyperactivation also include the alteration of cardiac calcium homeostasis, increased hypertrophy, and apoptosis of myocytes.