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Novel method for simultaneous determination of p-cresylsulphate and p-cresylglucuronide: clinical data and pathophysiological implications

Natalie Meert UGent, Eva Schepers UGent, Griet Glorieux UGent, MARIA VAN LANDSCHOOT UGent, Jan Goeman UGent, MARIA WATERLOOS UGent, Annemieke Dhondt UGent, Johan Van der Eycken UGent and Raymond Vanholder UGent (2012) NEPHROLOGY DIALYSIS TRANSPLANTATION. 27(6). p.2388-2396
abstract
Background. The uraemic retention solutes p-cresylsulphate (pCS) and p-cresylglucuronide (pCG), two conjugates of p-cresol, were never determined simultaneously. In the present paper, a high-performance liquid chromatography (HPLC) method was developed and used to quantify both compounds in parallel in an in vivo observational study and their in vitro effect was evaluated by flow cytometry. Methods. pCS and pCG were determined in serum. For the validation specificity, linearity, recovery, precision and the quantification limit were evaluated. In vivo, concentrations of both compounds were determined in 15 controls and 77 haemodialysis patients, as well as protein binding in the dialysed group and the reduction ratios during haemodiafiltration. In addition, the in vitro effect of the solutes on leucocyte free radical production at measured concentrations was assessed. Results. A fast and accurate HPLC method was developed to simultaneously quantify pCS and pCG. Both conjugates are retained in uraemia with a substantially higher total serum pCS in comparison to pCG (31.4 +/- 15.8 versus 7.3 +/- 6.5 mg/L) but also a substantial difference in protein binding (92.4 +/- 3.0 versus 8.3 +/- 4.4%) and in reduction ratio during post-dilution haemodiafiltration (37.4 +/- 7.1 versus 78.6 +/- 6.4%). pCG per se has no effect on leucocyte oxidative burst activity, whereas in combination with pCS, a synergistic activating effect was observed. Conclusions. Serum concentrations of pCS and pCG are elevated in uraemia. Both conjugates show a different protein binding, resulting in a different dialytic behaviour. Biologically, both conjugates are synergistic in activating leucocytes.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
dialysis adequacy, concentration, leucocyte activation, protein-bound uraemic toxins, removal by dialysis, UREMIC RETENTION SOLUTES, CHRONIC-RENAL-FAILURE, BETA-D-GLUCURONIDE, INDOXYL SULFATE, HEMODIALYSIS-PATIENTS, IN-VITRO, TOXINS, REMOVAL, CRESOL, CELLS
journal title
NEPHROLOGY DIALYSIS TRANSPLANTATION
Nephrol. Dial. Transplant.
volume
27
issue
6
pages
2388 - 2396
Web of Science type
Article
Web of Science id
000304832100041
JCR category
UROLOGY & NEPHROLOGY
JCR impact factor
3.371 (2012)
JCR rank
14/73 (2012)
JCR quartile
1 (2012)
ISSN
0931-0509
DOI
10.1093/ndt/gfr672
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
1979143
handle
http://hdl.handle.net/1854/LU-1979143
date created
2012-01-05 14:49:46
date last changed
2012-09-17 16:53:23
@article{1979143,
  abstract     = {Background. The uraemic retention solutes p-cresylsulphate (pCS) and p-cresylglucuronide (pCG), two conjugates of p-cresol, were never determined simultaneously. In the present paper, a high-performance liquid chromatography (HPLC) method was developed and used to quantify both compounds in parallel in an in vivo observational study and their in vitro effect was evaluated by flow cytometry. 
Methods. pCS and pCG were determined in serum. For the validation specificity, linearity, recovery, precision and the quantification limit were evaluated. In vivo, concentrations of both compounds were determined in 15 controls and 77 haemodialysis patients, as well as protein binding in the dialysed group and the reduction ratios during haemodiafiltration. In addition, the in vitro effect of the solutes on leucocyte free radical production at measured concentrations was assessed. 
Results. A fast and accurate HPLC method was developed to simultaneously quantify pCS and pCG. Both conjugates are retained in uraemia with a substantially higher total serum pCS in comparison to pCG (31.4 +/- 15.8 versus 7.3 +/- 6.5 mg/L) but also a substantial difference in protein binding (92.4 +/- 3.0 versus 8.3 +/- 4.4\%) and in reduction ratio during post-dilution haemodiafiltration (37.4 +/- 7.1 versus 78.6 +/- 6.4\%). pCG per se has no effect on leucocyte oxidative burst activity, whereas in combination with pCS, a synergistic activating effect was observed. 
Conclusions. Serum concentrations of pCS and pCG are elevated in uraemia. Both conjugates show a different protein binding, resulting in a different dialytic behaviour. Biologically, both conjugates are synergistic in activating leucocytes.},
  author       = {Meert, Natalie and Schepers, Eva and Glorieux, Griet and VAN LANDSCHOOT, MARIA and Goeman, Jan and WATERLOOS, MARIA and Dhondt, Annemieke and Van der Eycken, Johan and Vanholder, Raymond},
  issn         = {0931-0509},
  journal      = {NEPHROLOGY DIALYSIS TRANSPLANTATION},
  keyword      = {dialysis adequacy,concentration,leucocyte activation,protein-bound uraemic toxins,removal by dialysis,UREMIC RETENTION SOLUTES,CHRONIC-RENAL-FAILURE,BETA-D-GLUCURONIDE,INDOXYL SULFATE,HEMODIALYSIS-PATIENTS,IN-VITRO,TOXINS,REMOVAL,CRESOL,CELLS},
  language     = {eng},
  number       = {6},
  pages        = {2388--2396},
  title        = {Novel method for simultaneous determination of p-cresylsulphate and p-cresylglucuronide: clinical data and pathophysiological implications},
  url          = {http://dx.doi.org/10.1093/ndt/gfr672},
  volume       = {27},
  year         = {2012},
}

Chicago
Meert, Natalie, Eva Schepers, Griet Glorieux, Maria Van Landschoot, Jan Goeman, Maria Waterloos, Annemieke Dhondt, Johan Van der Eycken, and Raymond Vanholder. 2012. “Novel Method for Simultaneous Determination of P-cresylsulphate and P-cresylglucuronide: Clinical Data and Pathophysiological Implications.” Nephrology Dialysis Transplantation 27 (6): 2388–2396.
APA
Meert, N., Schepers, E., Glorieux, G., Van Landschoot, M., Goeman, J., Waterloos, M., Dhondt, A., et al. (2012). Novel method for simultaneous determination of p-cresylsulphate and p-cresylglucuronide: clinical data and pathophysiological implications. NEPHROLOGY DIALYSIS TRANSPLANTATION, 27(6), 2388–2396.
Vancouver
1.
Meert N, Schepers E, Glorieux G, Van Landschoot M, Goeman J, Waterloos M, et al. Novel method for simultaneous determination of p-cresylsulphate and p-cresylglucuronide: clinical data and pathophysiological implications. NEPHROLOGY DIALYSIS TRANSPLANTATION. 2012;27(6):2388–96.
MLA
Meert, Natalie, Eva Schepers, Griet Glorieux, et al. “Novel Method for Simultaneous Determination of P-cresylsulphate and P-cresylglucuronide: Clinical Data and Pathophysiological Implications.” NEPHROLOGY DIALYSIS TRANSPLANTATION 27.6 (2012): 2388–2396. Print.