Uremic Toxins and Hemodiafiltration: From Molecular Mechanisms to Clinical Outcomes

Stuard, Stefano; Hugh-Jones, Charles; Chatoth, Dinesh; Anger, Michael; Gagel, Alfred; Canaud, Bernard

doi:10.3390/toxins18070312

Open AccessReview

Uremic Toxins and Hemodiafiltration: From Molecular Mechanisms to Clinical Outcomes

by

Stefano Stuard

^1,*

,

Charles Hugh-Jones

²,

Dinesh Chatoth

²

,

Michael Anger

²,

Alfred Gagel

³

and

Bernard Canaud

⁴

¹

Global Medical Office, Fresenius Medical Care, 26020 Palazzo Pignano, Italy

²

Global Medical Office, Fresenius Medical Care, Waltham, MA 02451, USA

³

Global Research and Development, Fresenius Medical Care, 61352 Bad Homburg, Germany

⁴

School of Medicine, Montpellier University, 9 Rue des Carmelites, 34090 Montpellier, France

^*

Author to whom correspondence should be addressed.

Toxins 2026, 18(7), 312; https://doi.org/10.3390/toxins18070312

Submission received: 3 June 2026 / Revised: 14 July 2026 / Accepted: 15 July 2026 / Published: 17 July 2026

(This article belongs to the Special Issue New Insights in Uremic Toxins and Toxin-Related Outcomes in Chronic Kidney Disease)

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Abstract

Uremic syndrome results from the accumulation of biologically active solutes that contribute to inflammation, oxidative stress, endothelial dysfunction, cardiovascular disease, anemia, CKD–mineral and bone disorder, and protein-energy wasting in patients with end-stage kidney disease. While conventional hemodialysis efficiently removes small water-soluble compounds, clearance of middle molecules and protein-bound uremic toxins remains limited. Post-dilution hemodiafiltration (HDF) combines diffusion and convection to enhance removal across a broader molecular-weight spectrum. This review summarizes the mechanisms of uremic toxin accumulation, the biologic and clinical relevance of major retained solutes, and current evidence supporting improved toxin removal with HDF. Randomized trials, meta-analyses, and observational studies have associated HDF with reduced inflammatory burden, improved hemodynamic tolerance, and favorable clinical outcomes, supporting its role as an advanced strategy for targeting the broader spectrum of uremic toxicity.

Keywords: uremic toxins; hemodiafiltration; middle molecules; protein-bound uremic toxins; β2-microglobulin; end-stage kidney disease

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MDPI and ACS Style

Stuard, S.; Hugh-Jones, C.; Chatoth, D.; Anger, M.; Gagel, A.; Canaud, B. Uremic Toxins and Hemodiafiltration: From Molecular Mechanisms to Clinical Outcomes. Toxins 2026, 18, 312. https://doi.org/10.3390/toxins18070312

AMA Style

Stuard S, Hugh-Jones C, Chatoth D, Anger M, Gagel A, Canaud B. Uremic Toxins and Hemodiafiltration: From Molecular Mechanisms to Clinical Outcomes. Toxins. 2026; 18(7):312. https://doi.org/10.3390/toxins18070312

Chicago/Turabian Style

Stuard, Stefano, Charles Hugh-Jones, Dinesh Chatoth, Michael Anger, Alfred Gagel, and Bernard Canaud. 2026. "Uremic Toxins and Hemodiafiltration: From Molecular Mechanisms to Clinical Outcomes" Toxins 18, no. 7: 312. https://doi.org/10.3390/toxins18070312

APA Style

Stuard, S., Hugh-Jones, C., Chatoth, D., Anger, M., Gagel, A., & Canaud, B. (2026). Uremic Toxins and Hemodiafiltration: From Molecular Mechanisms to Clinical Outcomes. Toxins, 18(7), 312. https://doi.org/10.3390/toxins18070312

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

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Uremic Toxins and Hemodiafiltration: From Molecular Mechanisms to Clinical Outcomes

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