Uremic toxin p-cresol in terminal kidney failure patients

Sivkov A.V., Sinyuhin V.N., Bebeshko E.V.

Uremic toxins accumulate in patients with chronic kidney disease. These molecules may deteriorate the biochemical and physiological dysfunctions that define the uremic syndrome. Earlier studies concentrated on small water soluble and large middle molecules. However, the focus of the clinicians is shifting toward protein-bound uremic toxins recently. Protein-bound uremic toxins, including many kinds of different toxins, have been neglected for a long time and its clinical importance has been demonstrated in recent years. Para-cresol (p-cresol) belongs to the group of protein-bound uremic toxins and accumulates as renal function declines. In vivo, p-cresol exists predominantly as conjugated p-cresol sulfate and p-cresol glucuronide. However, previous reports demonstrated various toxic effects of total p-cresol in vitro. Their emphasis was placed on total p-cresol since the determination methods were based on deproteinization by acidification, leading to the disintegration of conjugates by hydrolysis. It was established that the production of conjugates correlates significantly with synthesis of maternal substance and its total concentration after hydrolysis reflects toxic effect. In our studies for quantification of total p-cresol we used high pressure liquid chromatography method after deproteinization of samples by acidification. It was found that in healthy control a total concentration of p-cresol was 6.8±3.4μmol/l. In haemodialysed patients it was 48±8.7μmol/l. In septic haemodialysed patients, there was a trend towards higher values (78±9.3μmol/l). It seems to us that very high concentrations of p-cresol in terminal kidney failure may be useful as a prognostic factor of inflammatory disease.

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