Effect of a medium cut-off dialyzer on protein-bound uremic toxins and mineral metabolism markers in patients on hemodialysis

Mark K Tiong; Rathika Krishnasamy; Edward R Smith; Colin A Hutchison; Elizabeth G Ryan; Elaine M Pascoe; Carmel M Hawley; Tim D Hewitson; Meg J Jardine; Matthew A Roberts; Yeoungjee Cho; Muh Geot Wong; Anne Heath; Craig L Nelson; Shaundeep Sen; Peter F Mount; Liza A Vergara; Peta-Anne Paul-Brent; David W Johnson; Nigel D Toussaint

doi:10.1111/hdi.12924

Effect of a medium cut-off dialyzer on protein-bound uremic toxins and mineral metabolism markers in patients on hemodialysis

Hemodial Int. 2021 Mar 28. doi: 10.1111/hdi.12924. Online ahead of print.

Authors

Mark K Tiong^{1

2}, Rathika Krishnasamy^{3

4}, Edward R Smith^{1

2}, Colin A Hutchison⁵, Elizabeth G Ryan^{4

6}, Elaine M Pascoe⁴, Carmel M Hawley^{4

7

8}, Tim D Hewitson^{1

2}, Meg J Jardine^{4

9

10

11

12}, Matthew A Roberts^{4

13}, Yeoungjee Cho^{4

7}, Muh Geot Wong^{10

11}, Anne Heath¹¹, Craig L Nelson^{14

15

16}, Shaundeep Sen¹², Peter F Mount¹⁷, Liza A Vergara⁴, Peta-Anne Paul-Brent⁴, David W Johnson^{4

7

8}, Nigel D Toussaint^{1

2}

Affiliations

¹ Department of Nephrology, The Royal Melbourne Hospital, Parkville, Australia.
² Department of Medicine (RMH), University of Melbourne, Parkville, Australia.
³ Department of Nephrology, Sunshine Coast University Hospital, Birtinya, Australia.
⁴ Australasian Kidney Trials Network, The University of Queensland, Brisbane, Australia.
⁵ Department of Medicine, Hawke's Bay Hospital, Hawkes Bay, New Zealand.
⁶ QCIF Facility for Advanced Bioinformatics, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia.
⁷ Department of Nephrology, Princess Alexandra Hospital, Brisbane, Australia.
⁸ Translational Research Institute, Brisbane, Queensland, Australia.
⁹ NHMRC Clinical Trials Centre, University of Sydney, Sydney, Australia.
¹⁰ The George Institute for Global Health, UNSW, Sydney, Australia.
¹¹ SAN Renal Dialysis Unit, Sydney Adventist Hospital, Sydney, Australia.
¹² Department of Nephrology, Concord Repatriation and General Hospital, Sydney, Australia.
¹³ Eastern Health Clinical School, Monash University, Melbourne, Australia.
¹⁴ Department of Nephrology, Western Health, Melbourne, Australia.
¹⁵ Department of Medicine, Western Health, University of Melbourne, Melbourne, Australia.
¹⁶ Western Health Chronic Disease Alliance, Western Centre for Health Research and Education, Western Health, St Albans, Australia.
¹⁷ Department of Nephrology, Austin Health, Melbourne, Victoria, Australia.

PMID: 33779046
DOI: 10.1111/hdi.12924

Abstract

Introduction: Hemodialysis (HD) with medium cut-off (MCO) dialyzers may expand molecular clearance, predominantly larger middle molecules (molecular weight 25-60 kDa). However, the impact of MCO dialyzers on long-term clearance of various other components of the uremic milieu is unknown. The tRial Evaluating Mid cut-Off Value membrane clearance of Albumin and Light chains in HemoDialysis patients (REMOVAL-HD) provided an opportunity to assess the effect of MCO dialyzers on protein-bound uremic toxins and novel markers of mineral metabolism.

Methods: This exploratory sub-study of REMOVAL-HD evaluated changes in protein-bound solutes (total and free indoxyl sulfate [IS] and p-cresyl sulfate [PCS]) and mineral metabolism markers (intact fibroblast growth factor-23 [iFGF23], fetuin-A and endogenous calciprotein particles [CPP-1 and CPP-2]). Mid-week, pre-HD serum samples were collected at baseline and after 12 and 24 weeks of MCO use in stable adult patients. Change from baseline to Week 12 and 24 was estimated using linear mixed effects models.

Findings: Eighty-nine participants were studied (mean age 67 ± 15 years, 38% female, 51% diabetic, median urine output 200 ml/24 h). Serum iFGF23 was reduced at Week 12 compared to baseline (-26.8% [95%CI -39.7, -11.1], p = 0.001), which was sustained at Week 24 (-21.7% [95%CI -35.7, -4.5], p = 0.012). There was no significant change in serum IS, PCS, fetuin-A, CPP-1, or CPP-2.

Discussion: The use of a MCO dialyzer over 24 weeks was associated with a sustained reduction in FGF23, while other measured components of the uremic milieu were not significantly altered. Further studies are required to determine whether FGF23 reduction is associated with improved patient outcomes.

Keywords: calciprotein particles; fetuin-A; fibroblast growth factor 23; medium cut-off dialyzer; protein-bound uremic toxins.

Abstract

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