Renin suppression persists in many patients with primary aldosteronism (PA) despite targeted medical treatment, which may indicate suboptimal mineralocorticoid receptor blockade. Hence renin is a suggested biomarker for medication titration in the Primary Aldosteronism Medical Treatment Outcome (PAMO) criteria. This study systematically reviewed the evidence on the association between post-treatment renin status and cardiovascular, renal, and mortality outcomes in medically treated patients with PA.
A systematic search of MEDLINE, Embase, CENTRAL and Web of Science was conducted on May 5th, 2025. Studies that investigated the association between post-treatment renin and clinical outcomes among medically treated patients with PA were included. The primary outcomes were the incidence of cardiovascular events, renal events, and mortality. Risk-of-bias was assessed using the QUIPS tool. Random-effects models were employed to estimate pooled hazard ratios (HRs) with 95% confidence intervals (CIs). Certainty-of-evidence was rated using the GRADE framework.
Twenty-four studies involving 6621 patients with PA on mineralocorticoid receptor antagonists were included. Most studies used plasm renin activity with a cut-off of 1.0 ng/mL/h to classify post-treatment renin as suppressed or unsuppressed. A meta-analysis demonstrated that unsuppressed post-treatment renin was associated with a lower risk of cardiovascular events with ≥5 years follow-up (pooled HR 0.33 [95%CI, 0.19–0.57], I2=0%, three studies, 756 patients; moderate certainty). No significant association was found with renal events (pooled HR 0.95 [95%CI, 0.51–1.77], two studies, I2=0%, very low certainty). One study reported a lower risk of mortality in patients with unsuppressed vs. suppressed post-treatment renin (HR 0.29 [95%CI, 0.09–0.98], 201 patients; moderate certainty).
In conclusion, unsuppressed renin following targeted medical therapy for PA is associated with a reduced risk of cardiovascular events, suggesting that normalisation of renin should serve as a therapeutic target. Prospective studies are warranted to confirm that medication titration to normalise renin improves clinical outcomes.