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

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

引言
血液透析（hemodialysis, HD）与血液透析滤过仅能低效清除血浆中的白细胞介素-6（interleukin-6, IL-6）与对甲酚（p-cresol），二者均为与终末期肾病（end stage renal disease）患者高心血管风险相关的蛋白结合性尿毒症毒素（protein-bound uremic toxins）。HFR Supra是一款双腔血液透析滤过系统（double-chamber hemodiafiltration system），其超滤液（ultrafiltrate）经可结合疏水性及蛋白结合性溶质的树脂吸附柱（resin cartridge）再生后回输至患者体内。本研究旨在评估该HFR吸附柱是否同样可结合超滤液中的总对甲酚与IL-6并将其清除。
方法
本研究纳入12名炎症状态慢性血液透析患者，在240分钟HFR治疗开始与结束时，分别采集吸附柱入口（UFin）与出口（UFout）处的超滤液样本，对比其中IL-6与对甲酚的水平。同时，采集12名健康志愿者的外周血单个核细胞（peripheral blood mononuclear cells, PBMC），通过评估超滤液样本诱导的IL-6 mRNA表达与蛋白释放变化，测定样本的促炎活性（pro-inflammatory activity）。此外，分别在HFR治疗前后采集外周血浆样本，检测其中IL-6与对甲酚的循环水平；并以常规血液透析（HD）作为对照进行比较。
结果
在HFR治疗开始与结束时，吸附柱出口处的超滤液样本中对甲酚与IL-6水平均低于入口处样本，提示二者可被吸附柱截留。与HFR治疗开始时采集的入口超滤液样本孵育的PBMC相比，以治疗结束时采集的出口超滤液样本孵育的PBMC中IL-6 mRNA表达与蛋白释放水平更低，提示超滤液经吸附柱处理后其促炎活性有所降低。HFR治疗后血浆总对甲酚水平下降约53%，常规HD治疗后下降约37%；两种透析方式均未改变患者的IL-6循环水平。
结论
本研究表明，HFR Supra吸附柱可截留超滤液中的总对甲酚与IL-6，并可降低血浆总对甲酚水平，但无法改变IL-6循环水平。
试验注册
ClinicalTrials.gov NCT01865773