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

IntroductionHemodialysis (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.MethodsWe 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.Resultsp-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.ConclusionsThis 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 RegistrationClinicalTrials.gov NCT01865773

Hemodiafiltration With Endogenous Reinfusion Improved Microinflammation and Endothelial Damage Compared With Online-Hemodiafiltration: A Hypothesis Generating Study

“…Hemodiafiltration with endogenous reinfusion (HFR) of regenerated ultrafiltrate as a substitution fluid combines adsorption, convection, and diffusion. HFR uses a dual dialyzer with an adsorbent resin cartridge between chambers . The first chamber is a high‐flux membrane where convection takes place.…”

“…p‐cresyl sulfate and indoxyl sulfate were measured from frozen serum aliquots. Total p‐cresyl (i.e., the sum of its free and protein‐bound fractions) and indoxyl sulfate were measured in serum with HPLC using a Hewlett‐Packard 1100 (Agilent Technologies, Inc., Santa Clara, CA, USA) high‐performance liquid chromatography system equipped in the standard configuration . IL‐6 and TNF‐α were measured using the Bio‐Plex Pro human cytokine panel (Bio‐Rad, Hercules, CA, USA).…”

“…Uremic toxin accumulation, chronic inflammation, endothelial injury and dysfunction, and enhanced reactive oxygen species (ROS) generation contribute to the high incidence of accelerated atherosclerosis and other cardiovascular complications in chronic kidney disease patients . Medium, high‐molecular weight and protein‐bound uremic toxins such as p‐cresyl sulfate and indoxyl sulfate have emerged as important risk factors for such morbidity and for mortality in dialysis patients . These toxins activate monocyte‐derived dendritic cells, i.e., CD14+CD16+ or CD14++CD16+ monocytes, which release proinflammatory cytokines that damage the endothelium .…”

Acute effect of one session of hemodiafiltration with endogenous reinfusion on uremic toxins and inflammatory mediators

“…Since significant hemoconcentration occurred during therapy, post-HFR concentrations of relatively large molecules were corrected depending on the change in the concentration of total serum protein (multiplying the ratio between the concentration of total serum protein at the beginning and at the end of therapy). 19,20 The results showed that hemoglobin and albumin remained unchanged during the HFR therapy process. There were significant reductions in p-CS and IS after a single HFR session with the mean reduction ratios of 40.91% (p = 0.0051) and 43.64% (p = 0.0051), respectively.…”

Radical Improvement of Signs and Symptoms in Systemic Lupus Erythematosus when Treated with Hemodiafiltration with Endogenous Reinfusion Dialysis

“…In contrast, the cartridge does not retain bicarbonate, amino acids and hydrosoluble vitamins. Other solutes, such as urea, creatinine, uric acid, Na+, K+, Ca2+, phosphate and bicarbonate, which are not adsorbed by the cartridge, are cleared, by diffusion, in the second chamber of the filter [ 6 , 7 , 8 ].…”