Longitudinal and cross-sectional associations of myocardial stress markers with kidney function and chronic kidney disease in the BiomarCaRE project

Given the complex relationship between cardiovascular disease (CVD) and chronic kidney disease (CKD), CVD-related markers may serve as CKD biomarkers. We examined associations of three major CVD-markers [mid-regional pro-adrenomedullin (MR-proADM), MR-pro-atrial natriuretic peptide (MR-proANP), and N-terminal pro-B-type natriuretic peptide (NT-proBNP)] with CKD. Cross-sectional analyses included up to 61,830 participants, and longitudinal analyses (NT-proBNP only) 4205 individuals. Kidney function was assessed by estimated glomerular filtration rate (eGFR) using creatinine, cystatin C, or both (eGFRcr-cys). Markers were categorized into four groups. Cross-sectional analyses found that higher levels of all three markers were consistently associated with lower eGFR and higher CKD prevalence. For example, per 1 standard deviation (SD) increase in log-transformed NT-proBNP, corresponding to a 2.71-fold increase in the original concentration, was associated with -2.35 (-2.49, -2.21) ml/min/1.73m2 lower eGFRcr-cys, and the highest NT-proBNP group had a 5.72-fold higher odds of CKDcr-cys (eGFRcr-cys < 60 ml/min/1.73m2) compared with the lowest. Associations with eGFR were stronger among participants with CVD and diabetes. In longitudinal analyses, participants with higher baseline NT-proBNP had faster declines in eGFR, with a 10-year decline of -1.37 (-1.77, -0.98) ml/min/1.73m2 eGFRcr-cys per 1 SD increase, and higher CKD incidence. These findings suggest MR-proADM, MR-proANP, and NT-proBNP as CKD biomarkers.