Proteome-Wide Changes in Blood Biomarkers During Hemodialysis

Abstract

IntroductionDuring hemodialysis, proteins in the blood can decrease in concentration due to diffusion, convective clearance, dialyzer adsorption, or cellular uptake, while others may increase in concentration due to production, cellular release, secretion, or ultrafiltration of water. We examined the impact of hemodialysis on blood protein concentrations on a proteome-wide scale. MethodsA nested cohort of 44 patients (25 male, 19 female) including 29 with intradialytic hypotension were selected from the prospective Hemodialysis Outcomes and SympToms assessment (HOST) cohort. 1,163 proteins were measured before and after a hemodialysis treatment using Olink. Pre- and post-dialysis concentrations were compared, and the impact of protein characteristics and intradialytic hypotension on protein concentration was evaluated. Results189 proteins (16%) significantly decreased and 54 (5%) significantly increased in concentration. Change in concentration was associated with protein 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 enrichment for cardiovascular biomarkers in those nominally associated with a drop in systolic blood pressure during treatment (P = 2.8 x 10-8). ConclusionsChanges in the blood proteome are detectable during hemodialysis on a high throughput scale. Protein properties and intradialytic hypotension events appear associated with changes in biomarker concentration. Larger proteome-wide biomarker studies may identify measures of dialysis adequacy and reveal pathological processes contributing to adverse effects of dialysis.