Kidney Week Educational Symposia-Uremic Toxin Removal with Dialysis: Effects of Middle Molecule Clearance on Clinical Outcomes

Video Transcription

Video Summary

The session reviews how “middle molecules” and other uremic toxins contribute to chronic kidney disease (CKD) complications and how dialysis technologies may better remove them. Anders Berg traces the middle molecule hypothesis to Belding Scribner’s “square meter-hour” concept, linking clearance of larger, slowly dialyzable solutes to membrane permeability and surface area. The European Working Group on Uremic Toxins has since cataloged 90+ toxins and grouped them by size/chemistry to guide removal strategies.<br /><br />Although urea is a small molecule, Berg argues it can still be toxic by generating cyanate, which carbamylates proteins and alters function. His group developed a mass-spectrometry assay for carbamylated albumin—an “HbA1c for uremia”—that correlates with time-averaged urea. Higher carbamylated albumin is associated with ~3-fold higher mortality in dialysis cohorts and predicts death and faster CKD progression in earlier-stage CKD. Levels can be reduced by intensified dialysis (e.g., frequent nocturnal dialysis) and possibly amino acid therapy.<br /><br />Jolanta Małyszko summarizes systemic effects of uremic toxins (cardiovascular, endocrine, immune, neurologic, GI) and highlights middle/large middle molecules (e.g., β2-microglobulin, cytokines, FGF23) implicated in inflammation and atherosclerosis. High-flux dialysis improves removal versus low-flux, but long-term outcome benefits remain inconsistent. Newer medium cut-off (MCO) membranes and expanded hemodialysis show better clearance of larger solutes (including free light chains) and short-term improvements in symptoms (e.g., pruritus, restless legs, quality of life), but definitive mortality data are lacking.<br /><br />Daniel Wiener emphasizes moving beyond Kt/V urea as “adequacy,” balancing enhanced middle molecule removal with safety (avoiding albumin loss). He reviews diffusion vs convection (hemodialysis vs hemofiltration/hemodiafiltration) and presents trial data suggesting MCO dialyzers increase larger middle molecule clearance with minimal albumin change. Overall, the field needs rigorous trials focused on patient-reported outcomes and survival.

Asset Subtitle

Moderators: Anders Berg

Speakers:

Introduction: History of Dialytic Clearance and the Importance of Middle Molecules - Anders Berg
Outcomes Associated with Middle Molecules in Chronic Dialysis - Jolanta Malyszko
Middle Molecule Removal with Chronic Dialysis: Safety and Efficacy of Current Approaches - Daniel Weiner

Meta Tag

Date 11/5/2021

Pathway 1 Dialysis

Session ID 408684

Session Type ES - Educational Symposium

Keywords

middle molecules

uremic toxins

chronic kidney disease complications

carbamylated albumin

cyanate carbamylation

high-flux hemodialysis

medium cut-off (MCO) membranes

expanded hemodialysis (HDx)

hemodiafiltration (HDF) convection

Kt/V urea adequacy