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.