Comparative analyses of adsorbed circulating proteins in the PMMA and PES hemodiafilters in patients on predilution online hemodiafiltration

PLoS One. 2024 Jul 19;19(7):e0299757. doi: 10.1371/journal.pone.0299757. eCollection 2024.

Abstract

Acute and chronic inflammation are common in patients with end-stage kidney disease (ESKD). So, the adsorption of pro-inflammatory cytokines by the hollow fiber of the dialysis membrane has been expected to modify the inflammatory dysregulation in ESKD patients. However, it remains to be determined in detail what molecules of fiber materials can preferably adsorb proteins from the circulating circuit. We aimed this study to analyze directly the adsorbed proteins in the polymethyl methacrylate (PMMA) and polyethersulfone (PES) membranes in patients on predilution online hemodiafiltration (OL-HDF). To compare the adsorbed proteins in the PMMA and PES hemodiafilters membrane, we initially performed predilution OL-HDF using the PES (MFX-25Seco) membrane while then switched to the PMMA (PMF™-A) membrane under the same condition in three patients. We extracted proteins from the collected hemodiafilters by extraction, then SDS-PAGE of the extracted sample, protein isolation, in-gel tryptic digestion, and nano-LC MS/MS analyses. The concentrations of adsorbed proteins from the PMMA and PES membrane extracts were 35.6±7.9 μg/μL and 26.1±9.2 μg/μL. SDS-PAGE analysis revealed distinct variations of adsorbed proteins mainly in the molecular weight between 10 to 25 kDa. By tryptic gel digestion and mass spectrometric analysis, the PMMA membrane exhibited higher adsorptions of β2 microglobulin, dermcidin, retinol-binding protein-4, and lambda-1 light chain than those from the PES membrane. In contrast, amyloid A-1 protein was adsorbed more potently in the PES membrane. Western blot analyses revealed that the PMMA membrane adsorbed interleukin-6 (IL-6) approximately 5 to 118 times compared to the PES membrane. These findings suggest that PMMA-based OL-HDF therapy may be useful in controlling inflammatory status in ESKD patients.

Publication types

  • Comparative Study

MeSH terms

  • Adsorption
  • Aged
  • Blood Proteins / analysis
  • Blood Proteins / chemistry
  • Female
  • Hemodiafiltration* / instrumentation
  • Hemodiafiltration* / methods
  • Humans
  • Kidney Failure, Chronic / blood
  • Kidney Failure, Chronic / therapy
  • Male
  • Membranes, Artificial*
  • Middle Aged
  • Polymers* / chemistry
  • Polymethyl Methacrylate* / chemistry
  • Sulfones* / chemistry
  • Tandem Mass Spectrometry / methods

Substances

  • Polymethyl Methacrylate
  • Sulfones
  • Polymers
  • Membranes, Artificial
  • polyether sulfone
  • Blood Proteins

Grants and funding

This work was supported by the MEXT Project to promote public utilization of advanced research infrastructure (Imaging Platform) (Grant Number JPMXS0410300220) and by the AMED project (Grant Number 21ak0101179), Japan. The funders had no role in the study design, data collection and analysis, preparation of the manuscript, or decision to publish. There was no additional external funding received for this study.