Plasma p-Cresol Lowering Effect of Sevelamer in Peritoneal Dialysis Patients: Evidence from a Cross-Sectional Observational Study.

p-Cresol is a by-product of the metabolism of aromatic aminoacid operated by resident intestinal bacteria. In patients with chronic kidney disease, the accumulation of p-cresol and of its metabolite p-cresyl-sulphate, that represents more than 95% of circulating p-cresol, causes endothelial dysfunction and ultimately increases the cardiovascular risk of these patients. Therapeutic strategies able to reduce plasma p-cresol levels are highly demanded but unfortunately not available yet. Because it has been reported that the phosphate binder sevelamer also sequesters p-cresol in vitro we hypothesized that it could do so also in peritoneal dialysis patients. To explore this hypothesis we measured total cresol plasma concentrations in 57 patients with end-stage renal disease on peritoneal dialysis patients, 29 receiving sevelamer for the treatment of hyperphosphatemia and 28 patients not assuming this drug. Among the patients not assuming sevelamer, 16 were treated with lanthanum whereas the remaining 12 received no drug because they were not hyperphosphatemic. When we compared total p-cresol plasma concentrations in these different groups of patients, we, we found that plasma p-cresol levels were significantly lower in patients receiving sevelamer than in subjects receiving lanthanum or no drug. Patients assuming sevelamer had also lower high sensitivity C-reactive protein serum concentrations compared to patients not assuming this drug. Multiple linear regression analysis showed that Conversely, no difference either in residual glomerular filtration rate, total weekly dialysis dose or serum phosphate levels were observed among the different groups. These results suggest that sevelamer could be an effective strategy to lower p-cresol circulating levels in peritoneal dialysis patients in which it could also favorably affect the cardiovascular risk because of its anti-inflammatory effect.