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Factors Beyond High-Molecular-Weight Toxin Removal That Might Affect Survival in Comparisons of High-Volume Hemodiafiltration with Hemodialysis

John T. Daugirdas

Toxins | Aug 25, 2026

Abstract

Abstract

Comparisons of hemodiafiltration with hemodialysis have indicated significantly improved survival when the substitution fluid volume is greater than 23 L per treatment. This survival benefit has been ascribed to better removal of high-molecular-weight uremic toxins. However, with hemodiafiltration, predialysis levels of some high-molecular-weight toxins are only modestly reduced and remain far above levels measured in subjects with normal kidney function. In the present review, the potential role of other factors associated with hemodiafiltration that may beneficially impact survival relative to that seen with hemodialysis is explored. Factors analyzed include removal of relatively small uremic toxins such as urea, phosphate, and oxalate, a reduced incidence of intradialytic hypotension in some studies, possibly related to lower extracorporeal circuit temperature, benefits associated with use of ultrapure dialysis solution, and potential benefits associated with avoidance of thrice-weekly saline infusion for priming, volume replacement, and rinse back. The survival benefit associated with each of these factors may be small, but collectively, they may have a clinical impact.

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John T. Daugirdas

first | University of Illinois Chicago | ORCID 0000-0002-0644-6842

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@article{Daugirdas2026Factors,
  title = {Factors Beyond High-Molecular-Weight Toxin Removal That Might Affect Survival in Comparisons of High-Volume Hemodiafiltration with Hemodialysis},
  author = {John T. Daugirdas},
  journal = {Toxins},
  year = {2026},
  doi = {10.3390/toxins18090365},
  url = {https://doi.org/10.3390/toxins18090365}
}

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