Yamamoto Suguru, Sato Mami, Sato Yoko, Wakamatsu Takuya, Takahashi Yoshimitsu, Iguchi Akira, Omori Kentaro, Suzuki Yasushi, Ei Isei, Kaneko Yoshikatsu, Goto Shin, Kazama Junichiro J, Gejyo Fumitake, Narita Ichiei
Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
Division of Blood Purification Therapy, Niigata University Medical and Dental Hospital, Niigata, Japan.
Artif Organs. 2018 Jan;42(1):88-93. doi: 10.1111/aor.12961. Epub 2017 Jul 13.
An accumulation of protein-bound uremic toxins (PBUTs) is one of major reasons for development of uremia-related complications. We examined the PBUT removal ability of a hexadecyl-immobilized cellulose bead (HICB)-containing column for patients undergoing hemodialysis. Adsorption of indoxyl sulfate (IS), a representative PBUT, to HICBs was examined in vitro. The HICB column was used in patients undergoing hemodialysis for direct hemoperfusion with a regular hemodialyzer. The serum IS, indole acetic acid (IAA), phenyl sulfate (PhS), and p-cresyl sulfate (PCS) levels were measured before and after passing the column. HICBs adsorbed protein-free (free) IS in a dose- and time-dependent manner in vitro (55.4 ± 1.4% adsorption of 1 millimolar, 251 µg/mL, IS for 1 h). In clinical studies, passing the HICB-containing column decreased the serum level of free IS, IAA, PhS, and PCS levels significantly (by 34.4 ± 30.0%, 34.8 ± 25.4%, 28.4 ± 18.0%, and 34.9 ± 22.1%, respectively), but not protein-bound toxins in maintenance hemodialysis patients. HICBs absorbed some amount of free PBUTs, but the clinical trial to use HICB column did not show effect to reduce serum PBUTs level in hemodialysis patients. Adsorption treatment by means of direct hemoperfusion with regular hemodialysis may become an attractive blood purification treatment to increase PBUT removal when more effective materials to adsorb PBUTs selectively will be developed.
蛋白结合尿毒症毒素（PBUTs）的蓄积是尿毒症相关并发症发生的主要原因之一。我们检测了含十六烷基固定化纤维素珠（HICB）的柱对接受血液透析患者的PBUT清除能力。在体外检测了代表性PBUT硫酸吲哚酚（IS）对HICB的吸附情况。HICB柱用于接受血液透析的患者，与常规血液透析器一起进行直接血液灌流。在通过该柱之前和之后测量血清IS、吲哚乙酸（IAA）、苯硫酸（PhS）和对甲酚硫酸（PCS）水平。在体外，HICB以剂量和时间依赖性方式吸附无蛋白（游离）IS（1毫摩尔、251μg/mL的IS吸附1小时，吸附率为55.4±1.4%）。在临床研究中，通过含HICB的柱显著降低了游离IS、IAA、PhS和PCS的血清水平（分别降低了34.4±30.0%、34.8±25.4%、28.4±18.0%和34.9±22.1%），但对维持性血液透析患者的蛋白结合毒素无影响。HICB吸收了一定量的游离PBUT，但使用HICB柱的临床试验未显示对降低血液透析患者血清PBUT水平有效果。当开发出更有效的选择性吸附PBUT的材料时，通过常规血液透析进行直接血液灌流的吸附治疗可能成为一种有吸引力的血液净化治疗方法，以增加PBUT的清除。
