The ARRplus: a model for renin-dependent and sex-specific aldosterone cut-offs that improves screening for primary aldosteronism.

OBJECTIVES

Screening for primary aldosteronism (PA) using the aldosterone:renin ratio (ARR) has suboptimal diagnostic accuracy, particularly in females. We assessed whether accuracy could be improved using sex-specific relationships of aldosterone with renin.

METHODS

Plasma aldosterone and renin were measured in 442 females and 491 males prospectively screened for PA. Patients were divided into test (n=717) and validation (n=216) cohorts. Sex-specific cut-offs for renin-dependent aldosterone concentrations and the ARR were developed using logistic regression models in the test cohort. Diagnostic performance of models in both cohorts was compared to that of the ARR.

RESULTS

Females without PA had higher (p<0.001) ARRs than males due to higher plasma aldosterone and lower renin concentrations. Consequently, rates of false-positives were higher (p<0.001) in females than males. At diagnostic sensitivities close to 95 % suitable for screening, and with sex-specific cut-offs for the ARR, specificities for the test cohort were 44 % in females compared to 73 % in males. Compared to the ARR, use of formulas (termed ARRplus) for sex-specific and renin-dependent cut-offs for aldosterone resulted in increased (p≤0.005) areas under receiver operating characteristic (ROC) curves for both sexes and enhanced specificity to 71 % in females and 82 % in males. Superiority of the ARRplus compared to the ARR was confirmed in the validation cohort according to ROC curve comparisons and 47-82 % reductions in false-positive results.

CONCLUSIONS

Renin-dependent and sex-specific aldosterone cut-offs using the ARRplus offer higher diagnostic accuracy than the ARR and considerably reduced rates of false-positives to minimize follow-up of screened patients, particularly women.