Tiong Mark K, Krishnasamy Rathika, Smith Edward R, Hutchison Colin A, Ryan Elizabeth G, Pascoe Elaine M, Hawley Carmel M, Hewitson Tim D, Jardine Meg J, Roberts Matthew A, Cho Yeoungjee, Wong Muh Geot, Heath Anne, Nelson Craig L, Sen Shaundeep, Mount Peter F, Vergara Liza A, Paul-Brent Peta-Anne, Johnson David W, Toussaint Nigel D
Department of Nephrology, The Royal Melbourne Hospital, Parkville, Australia.
Department of Medicine (RMH), University of Melbourne, Parkville, Australia.
Hemodial Int. 2021 Mar 28. doi: 10.1111/hdi.12924.
Hemodialysis (HD) with medium cut-off (MCO) dialyzers may expand molecular clearance, predominantly larger middle molecules (molecular weight 25-60 kDa). However, the impact of MCO dialyzers on long-term clearance of various other components of the uremic milieu is unknown. The tRial Evaluating Mid cut-Off Value membrane clearance of Albumin and Light chains in HemoDialysis patients (REMOVAL-HD) provided an opportunity to assess the effect of MCO dialyzers on protein-bound uremic toxins and novel markers of mineral metabolism.
This exploratory sub-study of REMOVAL-HD evaluated changes in protein-bound solutes (total and free indoxyl sulfate [IS] and p-cresyl sulfate [PCS]) and mineral metabolism markers (intact fibroblast growth factor-23 [iFGF23], fetuin-A and endogenous calciprotein particles [CPP-1 and CPP-2]). Mid-week, pre-HD serum samples were collected at baseline and after 12 and 24 weeks of MCO use in stable adult patients. Change from baseline to Week 12 and 24 was estimated using linear mixed effects models.
Eighty-nine participants were studied (mean age 67 ± 15 years, 38% female, 51% diabetic, median urine output 200 ml/24 h). Serum iFGF23 was reduced at Week 12 compared to baseline (-26.8% [95%CI -39.7, -11.1], p = 0.001), which was sustained at Week 24 (-21.7% [95%CI -35.7, -4.5], p = 0.012). There was no significant change in serum IS, PCS, fetuin-A, CPP-1, or CPP-2.
The use of a MCO dialyzer over 24 weeks was associated with a sustained reduction in FGF23, while other measured components of the uremic milieu were not significantly altered. Further studies are required to determine whether FGF23 reduction is associated with improved patient outcomes.
使用中截留量（MCO）透析器进行血液透析（HD）可能会扩大分子清除范围，主要是清除较大的中分子物质（分子量25 - 60 kDa）。然而，MCO透析器对尿毒症环境中其他各种成分的长期清除效果尚不清楚。血液透析患者中截留量膜白蛋白和轻链清除率评估试验（REMOVAL - HD）提供了一个机会，来评估MCO透析器对与蛋白质结合的尿毒症毒素以及矿物质代谢新标志物的影响。
REMOVAL - HD的这项探索性子研究评估了与蛋白质结合的溶质（总硫酸吲哚酚[IS]和对甲酚硫酸酯[PCS]以及游离硫酸吲哚酚和对甲酚硫酸酯）和矿物质代谢标志物（完整成纤维细胞生长因子23[iFGF23]、胎球蛋白 - A和内源性钙蛋白颗粒[CPP - 1和CPP - 2]）的变化。在稳定的成年患者中，于使用MCO透析器的第12周和24周的透析前，在周中采集血清样本。使用线性混合效应模型估计从基线到第12周和24周的变化。
对89名参与者进行了研究（平均年龄67±15岁，38%为女性，51%患有糖尿病，中位数尿量200 ml/24小时）。与基线相比，第12周时血清iFGF23降低（-26.8%[95%置信区间 - 39.7，-11.1]，p = 0.001），第24周时持续降低（-21.7%[95%置信区间 - 35.7，-4.5]，p = 0.012）。血清IS、PCS、胎球蛋白 - A、CPP - 1或CPP - 2无显著变化。
使用MCO透析器24周与FGF23持续降低相关，而尿毒症环境中其他测量成分未发生显著改变。需要进一步研究以确定FGF23降低是否与患者预后改善相关。
