Department of Health Technologies, Tallinn University of Technology, 19086 Tallinn, Estonia.
Centre of Nephrology, North Estonia Medical Centre, 13419 Tallinn, Estonia.
Int J Mol Sci. 2020 Feb 23;21(4):1522. doi: 10.3390/ijms21041522.
Tryptophan is an essential dietary amino acid that originates uremic toxins that contribute to end-stage kidney disease (ESKD) patient outcomes. We evaluated serum levels and removal during haemodialysis and haemodiafiltration of tryptophan and tryptophan-derived uremic toxins, indoxyl sulfate (IS) and indole acetic acid (IAA), in ESKD patients in different dialysis treatment settings. This prospective multicentre study in four European dialysis centres enrolled 78 patients with ESKD. Blood and spent dialysate samples obtained during dialysis were analysed with high-performance liquid chromatography to assess uremic solutes, their reduction ratio (RR) and total removed solute (TRS). Mean free serum tryptophan and IS concentrations increased, and concentration of IAA decreased over pre-dialysis levels (67%, 49%, -0.8%, respectively) during the first hour of dialysis. While mean serum total urea, IS and IAA concentrations decreased during dialysis (-72%, -39%, -43%, respectively), serum tryptophan levels increased, resulting in negative RR (-8%) towards the end of the dialysis session ( < 0.001), despite remarkable Trp losses in dialysate. RR and TRS values based on serum (total, free) and dialysate solute concentrations were lower for conventional low-flux dialysis ( < 0.001). High-efficiency haemodiafiltration resulted in 80% higher Trp losses than conventional low-flux dialysis, despite similar neutral Trp RR values. In conclusion, serum Trp concentrations and RR behave differently from uremic solutes IS, IAA and urea and Trp RR did not reflect dialysis Trp losses. Conventional low-flux dialysis may not adequately clear Trp-related uremic toxins while high efficiency haemodiafiltration increased Trp losses.
色氨酸是一种必需的膳食氨基酸,其代谢产物可引起尿毒症毒素的产生,从而影响终末期肾病(ESKD)患者的预后。我们评估了在不同透析治疗环境下,ESKD 患者血液透析和血液透析滤过过程中色氨酸和色氨酸衍生尿毒症毒素(吲哚硫酸酯[IS]和吲哚乙酸[IAA])的血清水平及其清除率。这项前瞻性多中心研究在欧洲的四个透析中心进行,共纳入 78 例 ESKD 患者。采用高效液相色谱法分析透析过程中采集的血液和废弃透析液样本,以评估尿毒症溶质及其减少率(RR)和总去除溶质(TRS)。与透析前相比,在透析的第一个小时内,游离血清色氨酸和 IS 浓度增加,而 IAA 浓度降低(分别为 67%、49%、-0.8%)。虽然在透析过程中,血清总尿素、IS 和 IAA 浓度降低(分别为-72%、-39%、-43%),但血清色氨酸水平升高,导致透析末期 RR 为负(-8%)(<0.001),尽管透析液中色氨酸有明显损失。基于血清(总、游离)和透析液溶质浓度的 RR 和 TRS 值,常规低通量透析(<0.001)更低。尽管中性色氨酸 RR 值相似,但高效血液透析滤过导致色氨酸损失比常规低通量透析高 80%。结论:与尿毒症溶质 IS、IAA 和尿素相比,血清色氨酸浓度和 RR 表现不同,色氨酸 RR 并不能反映透析时色氨酸的损失。常规低通量透析可能不能充分清除与色氨酸相关的尿毒症毒素,而高效血液透析滤过则会增加色氨酸的损失。