p-Cresol and cardiovascular risk in mild-to-moderate kidney disease.
OBJECTIVE
Cardiovascular disease is highly prevalent in chronic kidney disease. Traditional risk factors are insufficient to explain the high cardiovascular disease prevalence. Free p-cresol serum concentrations, mainly circulating as its derivative p-cresyl sulfate, are associated with cardiovascular disease in hemodialysis patients. It is not known if p-cresol is associated with cardiovascular disease in patients with chronic kidney disease not yet on dialysis.


METHODS
In a prospective observational study in 499 patients with mild-to-moderate kidney disease, we examined the multivariate association between p-cresol free serum concentrations and cardiovascular events.


RESULTS
After a mean follow-up of 33 mo, 62 patients reached the primary end point of fatal or nonfatal cardiovascular events. Higher baseline concentrations of free p-cresol were directly associated with cardiovascular events (univariate hazard ratio [HR] 1.79, P<0.0001). In multivariate analysis, p-cresol remained a predictor of cardiovascular events, independent of GFR and independent of Framingham risk factors (full model, HR 1.39, P=0.04).


CONCLUSIONS
These findings suggest that p-cresol measurements may help to predict cardiovascular disease risk in renal patients over a wide range of residual renal function, beyond traditional markers of glomerular filtration. Whether p-cresol is a modifiable cardiovascular risk factor in CKD patients remains to be proven.
Meijers
Björn K I
BK
Department of Medicine, Division of Nephrology and Laboratory for Gastro-Intestinal Research and Leuven Food Science and Nutrition Research Centre (LFoRCe), University Hospital Leuven, Leuven, Belgium.
Claes
Kathleen
K
Bammens
Bert
B
de Loor
Henriette
H
Viaene
Liesbeth
L
Verbeke
Kristin
K
Kuypers
Dirk
D
Vanrenterghem
Yves
Y
Evenepoel
Pieter
P
D000368:Aged; D001530:Belgium; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology* / Q000401:mortality / Q000503:physiopathology; D003408:Cresols / Q000097:blood*; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D053208:Kaplan-Meier Estimate; D007674:Kidney Diseases / Q000097:blood* / Q000150:complications / Q000401:mortality / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D013997:Time Factors
D015415:Biomarkers; D003408:Cresols; C032538:4-cresol