Toxicity of Free p-Cresol: A Prospective and Cross-Sectional Analysis

• DOI: 10.1373/49.3.470
• Publication Date: 2004-02-13T00:42:12Z
• Authors: Rita De Smet; Jacqueline Van Kaer; Bruno Van Vlem; Antoine De Cubber; Philippe Brunet; Norbert Lameire; Raymond Vanholder
• Keywords: Male; Blood Proteins; Middle Aged; 3. Good health; Cresols; 03 medical and health sciences; Cross-Sectional Studies; 0302 clinical medicine; Renal Dialysis; Luminescent Measurements; Multivariate Analysis; Leukocytes; Humans; Kidney Failure, Chronic; Regression Analysis; Female; Prospective Studies

AbstractBackground: Uremic syndrome is the consequence of the retention of solutes usually cleared by the healthy kidneys. p-Cresol can be considered a prototypic protein-bound uremic toxin. It is conceivable, analogous with drugs, that the non-protein-bound fraction of p-cresol exerts toxicity. This aspect had never been evaluated, nor have the factors influencing the free fraction of p-cresol.Methods: In a transsectional study we evaluated the relationship between prehemodialysis free p-cresol and the ratio of free to total p-cresol (F:T) to clinical and biological factors in 44 chronic renal failure patients. The evolution of free p-cresol was assessed prospectively in 12 patients showing a change in serum albumin of at least 5 g/L over time. Hospitalization days attributable to infection and the free p-cresol concentrations were noted over a 1-year period. The impact of free p-cresol in vitro on leukocyte functional capacity was evaluated by chemiluminescence.Results: We observed a correlation between total and free p-cresol (r = 0.84; P <0.001). In the multivariate analyses, free p-cresol and F:T showed a negative correlation with albumin. A shift from normal serum albumin to hypoalbumininemia in 12 patients led to an increase in free p-cresol from 5.9 ± 3.2 to 8.2 ± 4.5 μmol/L (P <0.05; 0.64 ± 0.35 to 0.89 ± 0.49 mg/L). Free p-cresol (P <0.05) was higher in the patients hospitalized for infectious disease. In vitro, free p-cresol was higher in a 25 g/L than in a 50 g/L albumin solution (P <0.05). Leukocyte chemiluminescence production was more inhibited in the low albumin (high free p-cresol) solution (28% ± 6% vs 21% ± 8%; P <0.05).Conclusions: Hypoalbuminemia and total p-cresol increase the free fraction of p-cresol. Patients hospitalized for infections have higher free p-cresol. In vitro, high free p-cresol has a negative impact on leukocyte chemiluminescence production. These data demonstrate the toxicity of free p-cresol.