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Abstract: PO0931

High-Throughput Analysis of Changes in Protein Biomarkers During Hemodialysis

Session Information

Category: Dialysis

  • 701 Dialysis: Hemodialysis and Frequent Dialysis

Authors

  • Lanktree, Matthew B., McMaster University, Hamilton, Ontario, Canada
  • Collister, David Thomas, University of Manitoba, Winnipeg, Manitoba, Canada
  • Pare, Guillaume, McMaster University, Hamilton, Ontario, Canada
  • Walsh, Michael, McMaster University, Hamilton, Ontario, Canada
Background

The impact of hemodialysis on the concentration of circulating protein biomarkers remains unclear. Biomarkers may decrease in concentration due to filter adsorption, diffusive clearance, or convective clearance, while others may increase in concentration due to production and secretion or intracellular release. Ultrafiltration of water is expected to also increase biomarker concentration. We sought to evaluate the impact of hemodialysis on 1,163 protein biomarkers in a high-throughput fashion.

Methods

A nested cohort of 44 patients (25 male, 19 female) including 29 with intradialytic hypotension and 15 without were selected from the prospective Hemodialysis Outcomes and Symptoms assessment (HOST) cohort. Intradialytic hypotension was stringently defined as a 60 mmHg drop in systolic blood pressure or a nadir systolic blood pressure of less than 70 mmHg during hemodialysis treatment. All hemodialysis treatments were done using the same hemodialysis filter type. 1,163 unique biomarkers were measured in each patient before and after a hemodialysis session using the Olink proximity extension assay (www.olink.com). Paired sample t-tests were used to compare pre- and post-dialysis concentrations with a Bonferroni-corrected significance threshold (P < 5 x 10-5).

Results

54 biomarkers (5%) significantly increased during hemodialysis treatment, while 243 (24%) significantly decreased. Change in biomarker concentration was significantly associated with biomarker molecular weight (r = 0.37, P = 2.8 x 10-16), isoelectric point (r = -0.26, P = 6.4 x 10-14), and pre-dialysis concentration (r = -0.21, P = 3.0 x 10-9). There was a significant enrichment of cardiovascular biomarkers in the top 20 biomarkers associated with drop in systolic blood pressure (P = 2.8 x 10-10), including Kidney Injury Molecule 1 (KIM1, P = 0.005).

Conclusion

Hemodialysis is associated with significant changes in protein biomarker concentrations related to protein properties and clinical events during treatment. These changes are measurable on a high-throughput platform. Further high-throughput biomarker studies could assess dialysis adequacy, test biomarker-symptom associations, and improve risk prognostication.

Funding

  • Private Foundation Support