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Abstract: TH-PO629

Cardiac Biomarkers and Kidney Function: A Bidirectional Mendelian Randomization Study

Session Information

Category: Hypertension and CVD

  • 1501 Hypertension and CVD: Epidemiology‚ Risk Factors‚ and Prevention

Authors

  • Robinson-Cohen, Cassianne, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Vartanian, Nicholas, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Akwo, Elvis Abang, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Hung, Adriana, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Ikizler, Talat Alp, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Bansal, Nisha, University of Washington, Seattle, Washington, United States
Background

Observational studies report strong associations between circulating cardiac biomarkers and kidney function. However, this evidence is vulnerable to bias from confounding and reverse causation. The aim of this study was to explore the causal direction of the relationship between kidney function and cardiac biomarkers using a bidirectional Mendelian Randomization (MR) approach.

Methods

Four cardiac biomarkers were studied, including NT-proBNP (N-terminal pro-B-type natriuretic peptide), galectin-3, growth differentiation factor-15 (GDF-15) and soluble ST2. Two-sample MR was used to estimate the causal effect of eGFR on these biomarkers and then performed in the opposite direction. We used as instruments genetic variants associated with creatinine-based eGFR in a large trans-ethnic genome-wide association study (GWAS) among individuals from the Chronic Kidney Disease Genetics Consortium (CKDGen, n=765,348) and UK Biobank (UKB, n=436,581), explaining up to 8.9% of the variance in eGFR, and GWAS of cardiac biomarkers from the SCALLOP consortium (n=21,757).

Results

Genetically predicted lower levels of eGFR were associated with higher levels of galectin-3 (p=2.3x10-9) and GDF-15 (p=3.9x10-4), but not NT-proBNP or soluble ST2 (Figure 1). In the other direction, there was evidence of a causal relationship between higher soluble ST2 and lower eGFR (p=0.0032), but not for any of the other biomarkers (Figure 2).

Conclusion

This MR study suggests that elevated galectin-3 and GDF-15, but not NT-proBNP or soluble ST2, are a consequence rather than a cause of reduced eGFR. Our findings also support a role for ST2 as a risk factor for reduced eGFR. Future work is needed to understand the mechanisms underlying these relationships and potential clinical utility of these biomarkers.

Funding

  • NIDDK Support