Short-term increase of glucose concentration in PDS results in extensive removal and high glycation level of vital proteins during continuous ambulatory peritoneal dialysis

Nephrol Dial Transplant. 2011 Aug;26(8):2674-83. doi: 10.1093/ndt/gfq793. Epub 2011 Feb 1.

Abstract

Background: The effect of clearance of so-called middle- and high-molecular weight proteins on clinical outcome of patients treated by peritoneal dialysis is still a matter of debate. In our present study, we investigated the impact of short-time alteration of the glucose concentration and the osmolarity of the peritoneal dialysis solution (PDS) on protein removal.

Methods: Peritoneal dialysis liquids (PDL) were collected from 19 well-characterized continuous ambulatory peritoneal dialysis (CAPD) patients treated with two types of PDS: Baxter (n = 10) and Fresenius (n = 9). The patients were treated with two different glucose concentration of each PDS in 4-h cycles. The depletion of the six interfering high-abundant proteins from the PDL samples was performed with the Multiple Affinity Removal LC Column-Human 6. The resulting protein fractions were analysed by 2D gel electrophoresis, differential in gel electrophoresis, mass spectrometry and 2D western blot.

Results: Proteomics investigation of the PDL fractions after depletion allowed the identification of 198 polypeptides of 424 excised spots. These polypeptides equates to 48 non-redundant proteins. Comparative analyses of 2D gel electrophoresis protein pattern revealed a clear correlation between protein removal and PDS glucose concentration and osmolarity. An increase for 4 h in the PDS osmolarity (with 43-51 mosmol/L) resulted qualitatively in 18-23% more protein removal in PDL. Moreover, 2D western blot analyses of the protein glycation pattern showed that the short-time increase in PDS glucose concentration (45-50 mM) resulted in significant alteration of the advanced glycosylation end products (AGEs) pattern.

Conclusions: The data presented in this study demonstrate a clear correlation between the short-time changes in glucose concentration and osmolarity of the PDS, and the augmentation of the protein removal and the appearance of AGEs during CAPD.

MeSH terms

  • Adult
  • Aged
  • Biological Transport
  • Biomarkers / metabolism*
  • Dialysis Solutions / chemistry*
  • Electrophoresis, Gel, Two-Dimensional
  • Female
  • Follow-Up Studies
  • Glucose / metabolism*
  • Glycation End Products, Advanced / metabolism*
  • Glycosylation
  • Humans
  • Kidney Failure, Chronic / therapy*
  • Male
  • Middle Aged
  • Osmolar Concentration
  • Peritoneal Dialysis, Continuous Ambulatory*
  • Prognosis
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Substances

  • Biomarkers
  • Dialysis Solutions
  • Glycation End Products, Advanced
  • Glucose