Uremic toxins in blood of end stage renal disease patients with dysbiosis of digestive tract

Numerous molecules, which are either excreted or metabolized by the kidneys, accumulate in patients with chronic kidney disease (CKD). These uremic retention molecules, contributing to the syndrome of uremia, may be classified according to their site of origin, that is: endogenous metabolism, microbial metabolism, or exogenous intake. Phenolic compounds such as phenylacetic acid, phenol, and p-cresol are generated by the partial breakdown of tyrosine and phenylalanine by a wide range of intestinal obligate or facultative anaerobes, including the genera Bacteroides, Lactobacillus, Enterobacter, Bifidobacterium, andespecially Clostridium. It is well known that probiotics can modify intestinal microbiota and thus provide clinical benefit for healthy individuals. However, their effect on patients with renal disease has not been fully studied. 18 patients undergoing hemodialysis (HD) treatment three times a week were enrolled in the study. Dysbiosis in feces of patients was detected by conventional culture-based methods. Serum p-cresol levels were measured by a protocol with a modification of HPLC method of Niwa. The results showed that HD patients without dysbiosis had the serum p-cresol level of about 26,5±6.7 mcmol/l, while patients with high serum p-cresol levels of 53,5±15,5 mcmol/l had > 10 5 colony-forming units (CFU) of Clostridium per gram of stool. Probiotic treatment appeared to have reduced the serum p-cresol level to 15.6±5.1 mcmol/l. This preliminary study demonstrates that HD patients with dysbiosis have high serum levels of p-cresol, and that probiotic treatment can reduce the serum level of this compound.