Free p-cresylsulphate is a predictor of mortality in patients at different stages of chronic kidney disease.
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.
Liabeuf
Sophie
S
INSERM ERI-12 (EA 4292) and the Clinical Research Centre-Division of Clinical Pharmacology, Amiens University Hospital, Amiens, France.
Barreto
Daniela V
DV
Barreto
Fellype C
FC
Meert
Natalie
N
Glorieux
Griet
G
Schepers
Eva
E
Temmar
Mohammed
M
Choukroun
Gabriel
G
Vanholder
Raymond
R
Massy
Ziad A
ZA
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
D015415:Biomarkers; D003408:Cresols; D013463:Sulfuric Acid Esters; C408690:4-cresol sulfate