Open Access Study protocol

Comparison of toxin removal outcomes in online hemodiafiltration and intra-dialytic exercise in high-flux hemodialysis: A prospective randomized open-label clinical study protocol

Vaibhav Maheshwari1, Lakshminarayanan Samavedham1, Gade Pandu Rangaiah1, Yijun Loy2, Lieng Hsi Ling34, Sunil Sethi45 and Titus Lau Wai Leong46*

Author Affiliations

1 Department of Chemical and Biomolecular Engineering, National University of Singapore, Singapore, Singapore

2 Rehabilitation Medicine, National University Hospital, Singapore, Singapore

3 National University Heart Center, Singapore, Singapore

4 Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

5 Department of Laboratory Medicine, National University Hospital, Singapore, Singapore

6 Division of Nephrology, Department of Medicine, National University Hospital, Singapore, Singapore

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BMC Nephrology 2012, 13:156  doi:10.1186/1471-2369-13-156

Published: 23 November 2012



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.


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.


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.

Trial registration number, NCT01674153

Hemodialysis; Hemodiafiltration; Intra-dialytic exercise; Toxin removal; Inter-compartmental resistance; Cardiac output; Regional blood flow model; Spent dialysate; Blood temperature