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

Evidence That p-Cresol and IL-6 Are Adsorbed by the HFR Cartridge: Towards a New Strategy to Decrease Systemic Inflammation in Dialyzed Patients?

Introduction Hemodialysis (HD) and hemodiafiltration clear only with a low efficiency the plasma from interleukin-6 and p-cresol, two protein-bound uremic toxins associated with high cardiovascular risk in end stage renal disease. HFR Supra is a double-chamber hemodiafiltration system in which the ultrafiltrate returns to the patient after its regeneration through a resin cartridge that binds hydrophobic and protein-bound solutes. In the present study, we evaluated whether the HFR cartridge can also bind total p-cresol and IL-6 and remove them from the ultrafiltrate. Methods We compared the levels of IL-6 and p-cresol in ultrafiltrate samples collected at the inlet (UFin) and at the outlet (UFout) of the cartridge at the start or at the end of a 240 min HFR session in 12 inflamed chronic HD patients. The pro-inflammatory activity of the ultrafiltrate samples was also determined by evaluating the changes that they induced in IL-6 mRNA expression and protein release in peripheral blood mononuclear cells from 12 healthy volunteers. IL-6 and p-cresol circulating levels were also assessed in peripheral plasma blood samples collected before and after HFR and, for comparison, a control HD. Results p-Cresol and IL-6 were lower in UFout than in UFin both at the start and at the end of the HFR session, suggesting that they were retained by the cartridge. IL-6 mRNA expression and release were lower in PBMC incubated with UFout collected at the end than with UFin collected at the start of HFR, suggesting that passage through the cartridge reduced UF pro-inflammatory activity. Plasma total p-cresol decreased by about 53% after HFR, and 37% after HD. IL-6 circulating values were unmodified by either these dialysis procedures. Conclusions This study shows that the HFR-Supra cartridge retains total p-cresol and IL-6 in the ultrafiltrate and lowers plasma total p cresol but not IL-6 levels. Trial Registration ClinicalTrials.gov NCT0186577

Simultaneous abdominal wall defect repair and Tenckhoff catheter placement in candidates for peritoneal dialysis

The presence of pre-existing abdominal wall defect (AWD) could represent a potential contraindication for peritoneal dialysis (PD) treatment. We report the results of our 6-year experience involving simultaneous repair of pre-existing AWD and catheter insertion for PD

Imaging of the peritoneum evaluated by 99mTc-icodextrin scintigraphy in peritoneal dialysis patients: preliminary data

In this study, we proposed a peritoneal scintigraphy with a different marker, the 99mTechnetium-Icodextrin, to evaluate the distribution of the dialysate within the peritoneal cavity in peritoneal dialysis (PD) patients

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 causes endothelial dysfunction and ultimately increases the cardiovascular risk of these patients. Therapeutic strategies to reduce plasma p-cresol levels are highly demanded but not available yet. Because it has been reported that the phosphate binder sevelamer 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, 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. Patients receiving sevelamer had plasma p-cresol and serum high sensitivity C-reactive protein concentrations significantly lower than those receiving lanthanum or no drug. Conversely, no difference was observed among the different groups either in residual glomerular filtration rate, total weekly dialysis dose, total clearance, urine volume, protein catabolic rate, serum albumin or serum phosphate levels. Multiple linear regression analysis showed that none of these variables predicted plasma p-cresol concentrations that, instead, negatively correlated with the use of sevelamer. 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 cardiovascular risk because of its anti-inflammatory effect