Renal Research Institute, New York, New York, USA,
Renal Research Institute, New York, New York, USA.
Blood Purif. 2022;51(8):639-648. doi: 10.1159/000517470. Epub 2021 Aug 10.
Constipation is prevalent in patients with kidney failure partly due to the use of medication, such as phosphate binders. We hypothesized that serum levels of gut microbiome-derived uremic toxins (UTOX) may be affected by the choice of phosphate binder putatively through its impact on colonic transit time. We investigated two commonly prescribed phosphate binders, sevelamer carbonate (SEV) and sucroferric oxyhydroxide (SFO), and their association with gut microbiome-derived UTOX levels in hemodialysis (HD) patients.
Weekly blood samples were collected from 16 anuric HD participants during the 5-week observational period. All participants were on active phosphate binder monotherapy with either SFO or SEV for at least 4 weeks prior to enrollment. Eight UTOX (7 gut microbiome-derived) and tryptophan were quantified using liquid chromatography-mass spectrometry. Serum phosphorus, nutritional, and liver function markers were also measured. For each substance, weekly individual levels, the median concentration per participant, and differences between SFO and SEV groups were reported. Patient-reported bowel movements, by the Bristol Stool Scale (BSS), and pill usage were assessed weekly.
The SEV group reported a 3.3-fold higher frequency of BSS stool types 1 and 2 (more likely constipated, p < 0.05), whereas the SFO group reported a 1.5-fold higher frequency of BSS stool types 5-7 (more likely loose stool and diarrhea, not significant). Participants in the SFO group showed a trend toward better adherence to phosphate binder therapy (SFO: 87.6% vs. SEV: 66.6%, not significant). UTOX, serum phosphorus, nutritional and liver function markers, and tryptophan were not different between the two groups.
There was no difference in the gut microbiome-derived UTOX levels between phosphate binders (SFO vs. SEV), despite SFO therapy resulting in fewer constipated participants. This pilot study may inform study design of future clinical trials and highlights the importance of including factors beyond bowel habits and their association with UTOX levels.
肾衰竭患者中便秘较为常见，部分原因是使用了药物，如磷酸盐结合剂。我们假设肠道微生物群衍生的尿毒症毒素（UTOX）的血清水平可能会受到磷酸盐结合剂选择的影响，因为它可能会影响结肠转运时间。我们研究了两种常用的磷酸盐结合剂，碳酸司维拉姆（SEV）和蔗糖铁氧体羟化物（SFO），以及它们与血液透析（HD）患者肠道微生物群衍生的 UTOX 水平的关系。
在 5 周的观察期内，每周从 16 名无尿 HD 参与者采集血液样本。所有参与者在入组前至少接受了 4 周的活性磷酸盐结合剂单药治疗，分别为 SFO 或 SEV。使用液相色谱-质谱法对 7 种 UTOX（7 种肠道微生物群衍生）和色氨酸进行定量。还测量了血清磷、营养和肝功能标志物。对于每种物质，报告了每周个体水平、每位参与者的中位数浓度以及 SFO 和 SEV 组之间的差异。每周评估患者的排便情况（Bristol 粪便量表，BSS）和药丸使用情况。
SEV 组报告 BSS 粪便类型 1 和 2（更可能便秘，p < 0.05）的频率高 3.3 倍，而 SFO 组报告 BSS 粪便类型 5-7（更可能出现稀便和腹泻，无统计学意义）的频率高 1.5 倍。SFO 组的参与者对磷酸盐结合剂治疗的依从性更好（SFO：87.6% vs. SEV：66.6%，无统计学意义）。两组之间 UTOX、血清磷、营养和肝功能标志物以及色氨酸无差异。
尽管 SFO 治疗导致更少的便秘参与者，但两种磷酸盐结合剂（SFO 与 SEV）之间的肠道微生物群衍生 UTOX 水平没有差异。这项初步研究可能为未来临床试验的研究设计提供信息，并强调了纳入超出肠道习惯及其与 UTOX 水平的关联的重要性。
