title: Free p-cresylsulphate is a predictor of mortality in patients at different stages of chronic kidney disease.
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.
authors.affiliation: INSERM ERI-12 (EA 4292) and the Clinical Research Centre-Division of Clinical Pharmacology, Amiens University Hospital, Amiens, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Liabeuf
authors.forename: Daniela V
authors.initials: DV
authors.lastname: Barreto
authors.forename: Fellype C
authors.initials: FC
authors.lastname: Barreto
authors.forename: Natalie
authors.initials: N
authors.lastname: Meert
authors.forename: Griet
authors.initials: G
authors.lastname: Glorieux
authors.forename: Eva
authors.initials: E
authors.lastname: Schepers
authors.forename: Mohammed
authors.initials: M
authors.lastname: Temmar
authors.forename: Gabriel
authors.initials: G
authors.lastname: Choukroun
authors.forename: Raymond
authors.initials: R
authors.lastname: Vanholder
authors.forename: Ziad A
authors.initials: ZA
authors.lastname: Massy
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood*; D003408:Cresols / Q000097:blood*; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000401:mortality*; D008297:Male; D011237:Predictive Value of Tests; D013463:Sulfuric Acid Esters / Q000097:blood*; D015996:Survival Rate
chemical_list: D015415:Biomarkers; D003408:Cresols; D013463:Sulfuric Acid Esters; C408690:4-cresol sulfate