Aldosterone-to-Renin Ratio and eGFR Decline

In a recent JASN article, Hundemer et al. report that elevated aldosterone-to-renin ratio (ARR) and suppressed renin are associated with steeper eGFR decline over 6.2 years in the CARTaGENE Population-based Cohort and Biobank (paired with CAHHM: Canadian Alliance for Healthy Hearts and Minds in our study)/Canadian Alliance for Healthy Hearts and Minds cohort.1 Extending the subclinical primary aldosteronism framework to kidney outcomes is timely and clinically relevant. We sought clarification regarding the handling of renin values below the assay's lower limit of reporting. The authors set concentrations below 1.0 ng/L (1.67 mU/L) to 0.9 ng/L (1.50 mU/L) to avoid over-inflation of the ARR.1 Because ARR interpretation is highly sensitive to the renin denominator—particularly in the suppressed range that defines a positive screen—analytic choices around censoring can meaningfully influence ARR distribution, categorization, and effect estimates.2,3 Could the authors report (1) the proportion of participants with renin below the reporting limit and (2) whether the ARR–eGFR slope association is robust to alternative, prespecified approaches for censored renin (e.g., limit of detection assay lower limit for renin measurement/√2 imputation, interval-censored methods, or analyses excluding individuals at the reporting limit)? Such sensitivity analyses would help readers gauge how much of the observed signal reflects biology versus analytical handling at the assay floor and may be particularly informative as the field debates renin-centered versus ARR-centered screening strategies.2–4 These additional details may further strengthen the interpretability and reproducibility of this important population-based observation.