title: Evidence that p-cresol and IL-6 are adsorbed by the HFR cartridge: towards a new strategy to decrease systemic inflammation in dialyzed patients?
abstract: BACKGROUND
  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.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01865773.
authors.affiliation: Department of Public Health, Section of Nephrology, Federico II University of Naples, Naples, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Riccio
authors.affiliation: Department of Neuroscience, Reproductive and Odontostomatologic Sciences, Section of Pharmacology, Federico II University of Naples, Naples, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Cataldi
authors.affiliation: Department of Public Health, Section of Nephrology, Federico II University of Naples, Naples, Italy.
authors.forename: Maristella
authors.initials: M
authors.lastname: Minco
authors.affiliation: Department of Public Health, Section of Nephrology, Federico II University of Naples, Naples, Italy.
authors.forename: Gennaro
authors.initials: G
authors.lastname: Argentino
authors.affiliation: Department of Public Health, Section of Nephrology, Federico II University of Naples, Naples, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Russo
authors.affiliation: Department of Public Health, Section of Nephrology, Federico II University of Naples, Naples, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Brancaccio
authors.affiliation: Department of Public Health, Section of Nephrology, Federico II University of Naples, Naples, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Memoli
authors.affiliation: Department of Pharmaceutical and Toxicological Chemistry, Federico II University of Naples, Naples, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Grumetto
authors.affiliation: Department of Cellular and Molecular Biology and Pathology, Federico II University of Naples, Naples, Italy.
authors.forename: Loredana
authors.initials: L
authors.lastname: Postiglione
authors.affiliation: Department of Clinical Medicine and Surgery, Federico II University of Naples, Naples, Italy.
authors.forename: Bruna
authors.initials: B
authors.lastname: Guida
authors.affiliation: Department of Public Health, Section of Nephrology, Federico II University of Naples, Naples, Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Memoli
mesh_terms: D000327:Adsorption; D000368:Aged; D003408:Cresols / Q000097:blood / Q000737:chemistry*; D005260:Female; D017583:Hemodiafiltration / Q000295:instrumentation / Q000379:methods; D015312:Hemodialysis Solutions / Q000737:chemistry; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000517:prevention & control; D015850:Interleukin-6 / Q000097:blood / Q000737:chemistry*; D007676:Kidney Failure, Chronic / Q000097:blood / Q000150:complications / Q000628:therapy; D008297:Male; D008875:Middle Aged; D012709:Serum Albumin / Q000737:chemistry
chemical_list: D003408:Cresols; D015312:Hemodialysis Solutions; D015850:Interleukin-6; D012709:Serum Albumin; C032538:4-cresol
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