In patients with heart failure, use of MRAs (spironolactone and eplerenone) was associated with lower appendicular skeletal muscle mass index and higher plasma renin activity in patients not receiving ACEi/ARB but not in patients receiving ACEi/ARB suggesting that MRA use without concurrent RAS inhibition, may contributing to upregulation of angiotensin II signaling, may be associated with reduction in muscle mass [155]. Here, REN is linked to heart failure.