Renin: Measurements, Correlates, and Associations With Long-Term Adverse Kidney Outcomes

Background: The association of renin with adverse kidney outcomes is largely unknown, and renin measurement strategies vary. We aimed to measure the clinical correlates of different renin measurements and the association between renin and incident chronic kidney disease (CKD), end-stage kidney disease (ESKD), and mortality. Methods: We performed a prospective cohort analysis of 9,420 participants in the Atherosclerosis Risk in Communities study followed from 1996 to 1998 through 2019. We estimated longitudinal associations of renin measured using SomaScan modified nucleotide aptamer assay with incident CKD, ESKD, and death using Cox proportional hazards models. Using samples from a subsequent study visit, we compared SomaScan renin with plasma renin activity (PRA) and renin level from Olink, and estimated associations with covariates using univariate and multivariable regression. Results: Higher SomaScan renin levels were associated with a higher risk of incident CKD (hazard ratio per two-fold higher [HR], 1.14; 95% confidence interval [CI], 1.09 to 1.20), ESKD (HR, 1.20; 95% CI, 1.03 to 1.41), and mortality (HR, 1.08; 95% CI, 1.04 to 1.13) in analyses adjusted for demographic, clinical, and socioeconomic covariates. SomaScan renin was moderately correlated with PRA (r=0.61) and highly correlated with Olink renin (r=0.94). SomaScan renin and PRA had similar clinical correlates except for divergent associations with age and beta-blocker use, both of which correlated positively with SomaScan renin but negatively with PRA. Conclusions: SomaScan aptamer-based renin level was associated with a higher risk of CKD, ESKD, and mortality. It was moderately correlated with PRA, sharing generally similar clinical covariate associations.