P-cresylsulphate, the main in vivo metabolite of p-cresol, activates leucocyte free radical production

Nephrol Dial Transplant. 2007 Feb;22(2):592-6. doi: 10.1093/ndt/gfl584. Epub 2006 Oct 13.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / blood
  • Cresols / metabolism*
  • Cresols / pharmacology*
  • Endotoxins / pharmacology
  • Escherichia coli
  • Free Radicals / metabolism
  • Humans
  • Leukocytes / drug effects*
  • Leukocytes / metabolism*
  • Respiratory Burst / drug effects*
  • Sulfuric Acid Esters / pharmacology*
  • Uremia / blood*


  • Biomarkers
  • Cresols
  • Endotoxins
  • Free Radicals
  • Sulfuric Acid Esters
  • 4-cresol
  • 4-cresol sulfate