title: Comparison of toxin removal outcomes in online hemodiafiltration and intra-dialytic exercise in high-flux hemodialysis: a prospective randomized open-label clinical study protocol.
abstract: BACKGROUND
  Maintenance hemodialysis (HD) patients universally suffer from excess toxin load. Hemodiafiltration (HDF) has shown its potential in better removal of small as well as large sized toxins, but its efficacy is restricted by inter-compartmental clearance. Intra-dialytic exercise on the other hand is also found to be effective for removal of toxins; the augmented removal is apparently obtained by better perfusion of skeletal muscles and decreased inter-compartmental resistance. The aim of this trial is to compare the toxin removal outcome associated with intra-dialytic exercise in HD and with post-dilution HDF.
  
  
  METHODS
  The main hypothesis of this study is that intra-dialytic exercise enhances toxin removal by decreasing the inter-compartmental resistance, a major impediment for toxin removal. To compare the HDF and HD with exercise, the toxin rebound for urea, creatinine, phosphate, and β2-microglobulin will be calculated after 2 hours of dialysis. Spent dialysate will also be collected to calculate the removed toxin mass. To quantify the decrease in inter-compartmental resistance, the recently developed regional blood flow model will be employed. The study will be single center, randomized, self-control, open-label prospective clinical research where 15 study subjects will undergo three dialysis protocols (a) high flux HD, (b) post-dilution HDF, (c) high flux HD with exercise. Multiple blood samples during each study session will be collected to estimate the unknown model parameters.
  
  
  CONCLUSIONS
  This will be the first study to investigate the exercise induced physiological change(s) responsible for enhanced toxin removal, and compare the toxin removal outcome both for small and middle sized toxins in HD with exercise and HDF. Successful completion of this clinical research will give important insights into exercise effect on factors responsible for enhanced toxin removal. The knowledge will give confidence for implementing, sustaining, and optimizing the exercise in routine dialysis care. We anticipate that toxin removal outcomes from intra-dialytic exercise session will be comparable to that obtained by standalone HDF. These results will encourage clinicians to combine HDF with intra-dialytic exercise for significantly enhanced toxin removal.
  
  
  BACKGROUND
  ClinicalTrials.gov number, NCT01674153.
authors.affiliation: Department of Chemical and Biomolecular Engineering, National University of Singapore, Singapore.
authors.forename: Vaibhav
authors.initials: V
authors.lastname: Maheshwari
authors.forename: Lakshminarayanan
authors.initials: L
authors.lastname: Samavedham
authors.forename: Gade Pandu
authors.initials: GP
authors.lastname: Rangaiah
authors.forename: Yijun
authors.initials: Y
authors.lastname: Loy
authors.forename: Lieng Hsi
authors.initials: LH
authors.lastname: Ling
authors.forename: Sunil
authors.initials: S
authors.lastname: Sethi
authors.forename: Titus Lau Wai
authors.initials: TL
authors.lastname: Leong
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003131:Combined Modality Therapy; D005081:Exercise Therapy; D005260:Female; D017583:Hemodiafiltration / Q000379:methods*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000175:diagnosis* / Q000534:rehabilitation*; D008297:Male; D008875:Middle Aged; D009862:Online Systems; D011446:Prospective Studies; D014118:Toxins, Biological / Q000097:blood*; D016896:Treatment Outcome; D055815:Young Adult; D001613:beta 2-Microglobulin / Q000097:blood*
chemical_list: D014118:Toxins, Biological; D001613:beta 2-Microglobulin