Cardiac and Stress Biomarkers and Chronic Kidney Disease Progression: The CRIC Study

Clin Chem. 2019 Nov;65(11):1448-1457. doi: 10.1373/clinchem.2019.305797. Epub 2019 Oct 2.


Background: Increases in cardiac and stress biomarkers may be associated with loss of kidney function through shared mechanisms involving cardiac and kidney injury. We evaluated the associations of cardiac and stress biomarkers [N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity troponin T (hsTnT), growth differentiation factor 15 (GDF-15), soluble ST-2 (sST-2)] with progression of chronic kidney disease (CKD).

Methods: We included 3664 participants with CKD from the Chronic Renal Insufficiency Cohort study. All biomarkers were measured at entry. The primary outcome was CKD progression, defined as progression to end-stage renal disease (ESRD) or 50% decline in estimated glomerular filtration rate (eGFR). Cox models tested the association of each biomarker with CKD progression, adjusting for demographics, site, diabetes, cardiovascular disease, eGFR, urine proteinuria, blood pressure, body mass index, cholesterol, medication use, and mineral metabolism.

Results: There were 1221 participants who had CKD progression over a median (interquartile range) follow-up of 5.8 (2.4-8.6) years. GDF-15, but not sST2, was significantly associated with an increased risk of CKD progression [hazard ratios (HRs) are per SD increase in log-transformed biomarker]: GDF-15 (HR, 1.50; 95% CI, 1.35-1.67) and sST2 (HR, 1.07; 95% CI, 0.99-1.14). NT-proBNP and hsTnT were also associated with increased risk of CKD progression, but weaker than GDF-15: NT-proBNP (HR, 1.24; 95% CI, 1.13-1.36) and hsTnT (HR, 1.11; 95% CI, 1.01-1.22).

Conclusions: Increases in GDF-15, NT-proBNP, and hsTnT are associated with greater risk for CKD progression. These biomarkers may inform mechanisms underlying kidney injury.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / blood
  • Cardiovascular Diseases / blood
  • Cohort Studies
  • Disease Progression*
  • Female
  • Glomerular Filtration Rate / physiology
  • Growth Differentiation Factor 15 / blood*
  • Humans
  • Interleukin-1 Receptor-Like 1 Protein / blood*
  • Male
  • Middle Aged
  • Natriuretic Peptide, Brain / blood*
  • Peptide Fragments / blood*
  • Proportional Hazards Models
  • Renal Insufficiency, Chronic / blood
  • Renal Insufficiency, Chronic / diagnosis*
  • Renal Insufficiency, Chronic / physiopathology
  • Risk Factors
  • Troponin T / blood*


  • Biomarkers
  • GDF15 protein, human
  • Growth Differentiation Factor 15
  • IL1RL1 protein, human
  • Interleukin-1 Receptor-Like 1 Protein
  • Peptide Fragments
  • Troponin T
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain