P1057UNTARGETED 1H NMR-BASED SERUM METABOLIC PROFILE ANALYSIS OF PATIENTS TREATED WITH HIGH VOLUME HEMODIAFILTRATION (HDF)

Abstract

Abstract Background and Aims Uremic toxins (UTs) accumulate in the circulation of patients with chronic kidney disease (CKD), contributing to poor outcomes. One of the main objectives of renal replacement therapies is the removal of UTs, and while HD is restricted to the clearance of low molecular weight UTs, hemodiafiltration (HDF) adds efficiency to the removal of medium molecular weight UTs through the association of diffusion and convection methods. Metabolomic analysis from nuclear magnetic resonance (NMR) spectra offers efficient data about metabolites profile, indicating the main features of HDF, and possibly highlighting the positive effects of this modality. Thus, the aim of the present study is to evaluate the profile of metabolites in the circulation of a cohort of patients undergoing HDF. Method From 97 individuals participating in the HDF arm of a randomized control trial (ClinicalTrials.gov Identifier: NCT02787161), we randomly (using Python language; NumPy library) selected 6 patients (mean age 49, 6 males, 44% diabetics, average duration of 245 minutes, blood flow of 400 mL/min, target convective volume of 22 L per treatment). Patient’s serum samples were collected in the beginning of the study (baseline) and 6 months. The samples were prepared with deuterium oxide, sodium trimethylsilylpropanesulfonate as internal standard (ð=0.0 ppm), and further submitted to 1H NMR spectra recorded with Bruker 600 MHz AVANCE III spectrometer in order to identify the patient’s metabolomic profile. Data was evaluated with t-test and results were then compared with the Human Metabolome Database (HMDB) for descending order of the Jaccard similarity score. Results A total of 50 metabolites were investigated. Interestingly, 2 metabolites were significantly (P<0.05) reduced in the serum after 6 months compared to baseline, acetate (3.3 ± 0.1) % and dimethylglyoxal (7.6 ± 0.1) % (Figure 1). In order to confirm the presence of these metabolites in human serum, further studies will be conducted with 2D 1H-13C-HSQCed NMR. Conclusion We observed a reduction of acetate and dimethylglyoxal levels after six months of HDF treatment, in comparison to baseline, most likely as a consequence of the increase in clearance of these molecules. Hypothetically these changes in solute removal could explain the positive effects of HDF on clinical outcomes, and further studies should address this potential benefit of the modality.