Free P-Cresylsulphate Is a Predictor of Mortality in Patients at Different Stages of Chronic Kidney Disease

Nephrol Dial Transplant. 2010 Apr;25(4):1183-91. doi: 10.1093/ndt/gfp592. Epub 2009 Nov 13.

Abstract

Background: Uraemic toxins are considered to be emerging mortality risk factors in chronic kidney disease (CKD) patients. p-Cresol (a prototype protein-bound uraemic retention solute) has been shown to exert toxic effects in vitro. Recently, it has been demonstrated that p-cresol is present in plasma as its sulphate conjugate, p-cresylsulphate. The present study evaluated the distribution of free and total p-cresylsulphate and sought to determine whether these parameters were associated with vascular calcification, arterial stiffness and mortality risk in a cohort of CKD patients.

Methods: One hundred and thirty-nine patients (mean +/- SD age: 67 +/- 12; males: 60%) at different stages of CKD (8% at Stage 2, 26.5% at Stage 3, 26.5% at Stage 4, 7% at Stage 5 and 32% at Stage 5D) were enrolled in this study.

Results: Baseline total and free p-cresylsulphate presented an inverse relationship with renal function and were significantly associated with vascular calcification. During the study period (mean follow-up period: 779 +/- 185 days), 38 patients died [including 22 from cardiovascular (CV) causes]. In crude survival analyses, free (but not total) p-cresylsulphate was shown to be a predictor of overall and CV death. Higher free p-cresylsulphate levels (>0.051 mg/100 mL; median) were associated with mortality independently of well-known predictors of survival such as age, vascular calcification, anaemia and inflammation.

Conclusions: Serum levels of free and total p-cresylsulphate (the main in vivo circulating metabolites of p-cresol) were elevated in later CKD stages. However, only free p-cresylsulphate seems to be a predictor of survival in CKD.

MeSH terms

  • Aged
  • Biomarkers / blood*
  • Cresols / blood*
  • Female
  • Humans
  • Kidney Failure, Chronic / blood
  • Kidney Failure, Chronic / mortality*
  • Male
  • Predictive Value of Tests
  • Sulfuric Acid Esters / blood*
  • Survival Rate

Substances

  • Biomarkers
  • Cresols
  • Sulfuric Acid Esters
  • 4-cresol sulfate