NDT Advance Access originally published online on October 13, 2006
Nephrology Dialysis Transplantation 2007 22(2):592-596; doi:10.1093/ndt/gfl584
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P-cresylsulphate, the main in vivo metabolite of p-cresol, activates leucocyte free radical production
1Renal Division, Department of Internal Medicine, University Hospital Gent and 2Laboratory for Organic and Bio-organic Synthesis, Department of Organic Chemistry, Gent University, Gent, Belgium
Correspondence and offprint requests to: R. Vanholder, Renal Division, Department of Internal Medicine, University Hospital, De Pintelaan 185, 9000 Gent, Belgium. Email: Raymond.Vanholder{at}UGent.be
| Abstract |
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Background. Chronic renal insufficiency is associated with the retention of solutes normally excreted by healthy kidneys. P-cresol, a prototype protein-bound uraemic retention solute, has been shown to exert toxic effects in vitro. Recently, however, it has been demonstrated that p-cresol in the human body is conjugated, with p-cresylsulphate as the main metabolite.
Methods. The present study evaluates the effect of p-cresylsulphate on the respiratory burst activity of leucocytes.
Results. P-cresylsulphate significantly increased the percentage of leucocytes displaying oxidative burst activity at baseline. Oxidative burst activity of stimulated leucocytes was however not affected. In contrast, p-cresol had no effect on the leucocytes at baseline, but inhibited leucocytes burst activity after stimulation.
Conclusion. The present study demonstrates, for the first time, that p-cresylsulphate, the main in vivo metabolite of p-cresol, has a pro-inflammatory effect on unstimulated leucocytes. This effect could contribute to the propensity to vascular disease in the uraemic population.
Keywords: immune response; leucocytes; oxidative burst activity; uraemic toxins; vascular disease
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