Renin normalization may predict improved outcomes in medically treated primary aldosteronism

medwireNews: Having unsuppressed renin after targeted mineralocorticoid receptor antagonist (MRA) therapy may reduce the risk for cardiovascular events and all-cause mortality in patients with primary aldosteronism, show data from a systematic review and meta-analysis.

The findings “support current expert recommendations that normalisation of post-treatment renin should be targeted to mitigate the risk of cardiovascular events,” write Jun Yang (Hudson Institute of Medical Research, Clayton, Victoria, Australia) and co-authors in The Lancet Diabetes & Endocrinology.

In the primary meta-analysis, which included data from four studies including 874 patients with primary aldosteronism on MRAs, the researchers found that individuals with unsuppressed post-treatment renin had a significant 57% lower risk for cardiovascular events than those with suppressed renin. Across the studies, renin suppression was typically defined as plasma renin activity below 1.0 ng/mL per hour.

A subgroup meta-analysis of data from three studies with 754 patients revealed that unsuppressed post-treatment renin was associated with a significant 67% lower risk for cardiovascular events after 5 or more years of follow-up than suppressed renin, but no significant association was found for patients with less than 5 years of follow-up.

However, no studies included follow-up periods between 2 years and 4 years, meaning that “the minimum duration required to detect a significant difference in cardiovascular outcomes between patients with unsuppressed versus suppressed post-treatment renin remains uncertain,” the authors remark.

There was no significant association between plasma renin activity and renal outcomes in two studies involving 276 patients, while one study, among 201 patients, reported that unsuppressed post-treatment renin was associated with a significant 71% lower risk for all-cause mortality versus suppressed renin.

In addition, meta-analyses of secondary outcomes showed that individuals with unsuppressed post-treatment renin had significantly lower systolic and diastolic blood pressure than those with suppressed renin (pooled mean difference –4.4 mmHg and –3.3 mmHg, respectively; n=10 studies, 2659 patients).

Yang et al say this finding further supports “the prognostic value of aiming for renin normalization.”

The investigators also found that patients with unsuppressed post-treatment renin received higher MRA doses than those with suppressed renin after treatment (pooled mean difference 3.4 mg; n=8 studies, 2149 patients), and that spironolactone use was higher in in the former group than in the latter (71 vs 57%; n=7 studies, 2026 patients).

Of note, the team generally judged certainty of evidence as low for each of the outcomes and found that none of the studies had a low risk for bias across all domains in the Quality in Prognostic Studies (QUIPS) tool. Indeed, many had high risk in the QUIPS Domain 5, indicating bias due to confounding.

Yang and colleagues conclude: “Our findings reinforce the clinical importance of post-treatment renin as a biomarker to assess the efficacy of medical treatment for primary aldosteronism, particularly for cardiovascular protection.

“However, limitations related to confounding and sparse data on renal outcomes warrant caution.”

They add: “Prospective trials are warranted to confirm whether medication titration improves clinical outcomes through normalisation of post-treatment renin.”

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Lancet Diabetes Endocrinol 2025; doi:10.1016/S2213-8587(25)00263-3