INTRODUCTION
The renin-angiotensin-aldosterone system (RAAS) is a complex neuroendocrine system that regulates salt and water homeostasis, blood pressure (BP) and tissue proliferation amongst several other actions [1]. Blockers of RAAS are a cornerstone in the treatment of hypertension working at least in part by reducing the formation or blocking the effects of angiotensin II and plasma aldosterone (PA) which is recognized as an independent cardiovascular risk factor promoting cardiovascular and renal inflammation, fibrosis, and remodelling [2].
Compared to RAAS inhibitory drugs, diuretics have more complex mechanism of action [3] which includes an initial reduction in plasma volume and a sustained decline in peripheral resistance, thereby improving the underlying haemodynamic defect of hypertension [4–7]. Under acute and chronic conditions, diuretics induce an increase in plasma renin activity (PRA) [8] but whether diuretics also increases PA has been debated [9] . In fact, apart from the level of activation of the RAAS; potassium [10–12] (which is also affected by diuretic treatment) plays an important role in the regulation of PA production and some diuretics (such as mineralocorticoid receptor antagonists) are known to have direct inhibitory action on aldosterone formation.
Therefore, the main objective of the present study was to perform a systematic review and meta-analysis of randomised clinical trials (RCT) where diuretics were used to treat hypertension and measurements of PA were available before and after diuretic treatment to address if they lead to a sustained increased in PA. The secondary outcomes were to establish (a) if there is correlation between difference in PA and plasma potassium between diuretic classes (b) if the decrease in BP relates to the difference in PA.