Abstract

Uremia has been a rapidly increasing health problem in China. Hemodialysis (HD) is the main renal replacement therapy for uremia. The results of large-scale clinical trials have shown that the HD pattern is crucial for long-term prognosis of maintenance hemodialysis (MHD) in uremic patients. Plasma metabolism is very important for revealing the biological insights linked to the therapeutic effects of the HD pattern on uremia. Alteration of plasma metabolites in uremic patients in response to HD therapy has been reported. However, HD-pattern-dependent changes in plasma metabolites remain poorly understood. To this end, a capillary electrophoresis-time of flight mass spectrometry (CE-TOF/MS)-based metabolomics method was performed to systemically study the differences between HD and high flux hemodialysis (HFD) on plasma metabolite changes in patients. Three hundred and one plasma samples from three independent human cohorts (i.e., healthy controls, patients with pre-HD/post-HD, and patients with pre-HFD/post-HFD) were used in this study. Metabolites significantly changed (p < 0.05) after a single HD or HFD process. However, 11 uremic retention solutes could be more efficiently removed by HFD. Our findings indicate that a CE-TOF/MS-based metabolomics approach is promising for providing novel insights into understanding the effects of different dialysis methods on metabolite alterations of uremia.

Highlights

  • Chronic kidney disease (CKD) is a worldwide health problem in a rapidly increasing population and can develop into end-stage renal disease (ESRD)[1]

  • Differentiate CKD stages, Shah et al investigated plasma metabolites in 4 stages of CKD by gas and liquid chromatography coupled to mass spectrometry[10]

  • No significant differences existed between the HFD group and the HD group including age, gender, primary disease, dialysis age, hemoglobin, albumin, Glutamicpyruvic transaminase, pre/post-dialysis blood urea nitrogen (BUN) and pre/post-dialysis serum creatinine (Scr), Kt/V, pre-dialysis serum potassium, sodium, calcium, and phosphorus

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Summary

Introduction

Chronic kidney disease (CKD) is a worldwide health problem in a rapidly increasing population and can develop into end-stage renal disease (ESRD)[1]. Much attention has been paid to ESRD and dialysis from different aspects, the particular alterations of small molecular hydrophilic metabolites in uremic patients after one course of different types of dialysis (e.g., HD and high flux hemodialysis (HFD)) still have rarely been studied. Differentiate CKD stages, Shah et al investigated plasma metabolites in 4 stages of CKD by gas and liquid chromatography coupled to mass spectrometry[10]. A capillary electrophoresis-time of flight mass spectrometry (CE-TOF/MS)-based metabolomics approach was used to define small molecular hydrophilic metabolites in plasma from different uremic patients before (pre-) and after (post-) HD and HFD (e.g., pre-HD, post-HD, pre-HFD, post-HFD) and compare those results to healthy controls. Support Vector Machines-Recursive Feature Elimination (SVM-RFE)[12] was used for statistical analysis of the current metabolomics data

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