Paired Predialysis and Postdialysis Investigation of Global Metabolomics (P/paraDIGM): Pilot Results

Background: Urea is recognized as a limited marker of uremic toxin burden and dialysis clearance. In children receiving chronic hemodialysis (HD), we used metabolomic profiling to assess: 1) global metabolic changes pre/post-HD, and 2) clearance of a uremic toxin panel. Methods: P/paraDIGM recruited participants receiving chronic HD at a large children’s hospital. Participants were eligible if they were >1 year-old, weighed >10kg, hemoglobin >8g/dL, and had been on chronic HD for >1-month. Pre- and post-HD blood samples were collected for up to 6 HD sessions per participant. Plasma global metabolomic profiling was completed in one batch at Metabolon Inc. (Durham, NC). Metabolite reduction ratios (RRs) were calculated similar to urea reduction ratio (URR) using the formulaL (1-[pre/post-HD level])*100. We selected 14 novel or candidate uremic toxins for targeted analyses (listed in Table 1). Linear mixed-effects models (LME) adjusted for age and sex and repeated measures correlation were applied to assess the associations of toxin RR with URR. Results: There were 10 study participants in whom paired pre- and post-HD blood samples were obtained for 49 HD sessions. Median (interquartile range) age was 11.7 (3.9, 16.1) years and dialysis vintage was 1.6 (0.7, 2.2) years. 50% of participants were male and 70% were anuric. A total of 1580 metabolites were quantified. Based on median RR after HD, 522 metabolites had >50% reduction, 552 had <20% change, 184 had >50% increase. 28 lysophospholipids (involved in inflammatory signaling) were enriched among the metabolites increased after HD (hypergeometric distribution test p-value <0.0001). Table 1 shows how the 14 toxin RRs associate with URR. Conclusion: We showed the feasibility of using metabolomics for pre/post-HD analyses. Inflammatory lysophospholipids increased after HD runs.Strong linear correlations between toxin RR and URR does not imply equivalent clearance. These data contribute to the recognition of urea being a limited marker of uremia and dialysis clearance. Funding: NIDDK Support - NIDDK Support, NIDDK Support