Glycoxidation and inflammatory markers in patients on treatment with PMMA-based protein-leaking dialyzers

Kidney Int. 2005 Feb;67(2):750-9. doi: 10.1111/j.1523-1755.2005.67138.x.

Abstract

Background: High-molecular-weight solutes such as glycation and oxidation protein products are putative proinflammatory mediators found in the uremic blood. The elimination of these and other large solutes by protein-leaking dialyzers (PLD) might help to correct the inflammatory status of maintenance hemodialysis (HD) patients.

Methods: Two matched groups of 13 standard 3 times/week HD patients were treated for 6 months with PMMA-based PLD and non-protein-leaking dialyzers (NPLD), respectively. At baseline, 1, 3, and 6 months, we measured the blood levels of the inflammatory cytokines IL-1beta, TNF-alpha, IL-6, the acute-phase protein C-reactive protein (CRP), the adhesion molecules ICAM-1, VCAM-1, and selectine-E, the chemotaxis factors MCP-1, and the glycation and oxidation protein end products pentosidine, protein carbonyls, and AOPP.

Results: In all the patients at baseline, pre-HD levels of glycation and oxidation protein markers, and inflammatory parameters were significantly higher than in healthy control subjects (P < 0.01 or greater). After 6 months, in the group on treatment with PLD, but not in that on NPLD, there was a significant decrease (P < 0.05 or greater) of pre-HD values of total pentosidine (mainly represented by pentosidine in serum albumin; -43%), protein carbonyls (-42%), AOPP (-38%), and the inflammatory cytokines IL-1beta (-49%), IL-6 (-39%), and TNF-alpha (-20%), while IL-10 and INF-gamma increased by 67% and 37%, respectively. Proinflammatory cytokines, and particularly IL-6, showed a positive correlation with the levels of circulating pentosidine. Protidemia was not significantly modified at the end of the study in both the groups.

Conclusion: The results in this pilot study show that the removal of large solutes by PLD can improve some indices of chronic inflammation in HD patients. Further studies are required to determine the relevance of the individual solutes removed with PLD as proinflammatory mediators in the uremic environment.

MeSH terms

  • Adult
  • Aged
  • Arginine / analogs & derivatives*
  • Arginine / metabolism
  • Blood Proteins / metabolism*
  • Chemokine CCL2 / blood
  • Female
  • Glycosylation
  • Humans
  • Inflammation / etiology*
  • Lysine / analogs & derivatives*
  • Lysine / metabolism
  • Male
  • Malnutrition / etiology
  • Membranes, Artificial*
  • Middle Aged
  • Oxidation-Reduction
  • Polymethyl Methacrylate
  • Protein Binding
  • Renal Dialysis / adverse effects
  • Renal Dialysis / instrumentation*

Substances

  • Blood Proteins
  • CCL2 protein, human
  • Chemokine CCL2
  • Membranes, Artificial
  • Polymethyl Methacrylate
  • Arginine
  • pentosidine
  • Lysine