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

**Authors:** Jie-sheng Lin, Tanja Zeller, Wolfgang Koenig, Pekka Jousilahti, Frank Kee, Licia Iacoviello, Hugh Tunstall-Pedoe, Stefan Söderberg, Giancarlo Cesana, Luigi Palmieri, Veikko Salomaa, Julia de Man Lapidoth, Roberto De Ponti, Chiara Donfrancesco, Thiess Lorenz, Kari Kuulasmaa, Stefan Blankenberg, Annette Peters, Barbara Thorand

PMC · DOI: 10.1038/s41598-026-37377-2 · Scientific Reports · 2026-02-23

## TL;DR

This study shows that heart-related stress markers are linked to reduced kidney function and higher risk of chronic kidney disease.

## Contribution

The study identifies three CVD markers as potential biomarkers for CKD through large-scale cross-sectional and longitudinal analyses.

## Key findings

- Higher levels of MR-proADM, MR-proANP, and NT-proBNP are associated with lower eGFR and higher CKD prevalence.
- NT-proBNP is linked to faster eGFR decline and higher CKD incidence over 10 years.
- Associations between markers and eGFR are stronger in individuals with CVD and diabetes.

## Abstract

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.

The online version contains supplementary material available at 10.1038/s41598-026-37377-2.

## Linked entities

- **Diseases:** cardiovascular disease (MONDO:0004995), chronic kidney disease (MONDO:0005300), diabetes (MONDO:0005015)

## Full-text entities

- **Genes:** MME (membrane metalloendopeptidase) [NCBI Gene 4311] {aka CALLA, CD10, CMT2T, NEP, SCA43, SFE}, NPPA (natriuretic peptide A) [NCBI Gene 4878] {aka ANF, ANP, ATFB6, ATRST2, CDD, CDD-ANF}, NPPB (natriuretic peptide B) [NCBI Gene 4879] {aka BNP, Iso-ANP}, ADM (adrenomedullin) [NCBI Gene 133] {aka AM, PAMP}, CST3 (cystatin C) [NCBI Gene 1471] {aka ADLDWA, ARMD11, HEL-S-2}, REN (renin) [NCBI Gene 5972] {aka ADTKD4, HNFJ2, RTD}
- **Diseases:** albuminuria (MESH:D000419), cardiorenal syndrome (MESH:D059347), hypertension (MESH:D006973), ESKD (MESH:D007676), myocardial ischemia (MESH:D017202), CVD (MESH:D002318), Myocardial Infarction (MESH:D009203), impaired kidney function (MESH:D007674), HF (MESH:D006333), cardiac pathology (MESH:D006331), volume overload (MESH:D019190), inflammatory (MESH:D007249), Diabetes (MESH:D003920), CKD (MESH:D051436), angina pectoris (MESH:D000787), obesity (MESH:D009765), stroke (MESH:D020521), function (MESH:D003291), kidney function (MESH:D007680)
- **Chemicals:** LCZ696 (MESH:C549068), cr-cys (-), natriuretic peptides (MESH:D045265), cys (MESH:D003545), alcohol (MESH:D000438), Creatinine (MESH:D003404), triglycerides (MESH:D014280)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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Source: https://tomesphere.com/paper/PMC12929796