Gut Microbiome-Derived Uremic Toxin Levels in Hemodialysis Patients on Different Phosphate Binder Therapies.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

A brief review of external mass balance and internal calcium redistribution in dialysis patients--is calcium a uremic toxin?

Recent debates between 2 schools of thought on calcium mass balance in dialysis patients and its relevance to disease--one emphasizing external calcium mass balance, and the other, internal calcium redistribution--have created controversy. Due to decreased ability to excrete calcium and loss of endocrine function by the kidney, patients suffering from chronic kidney disease, particularly when requiring dialysis, demonstrate varying degrees of positive or negative calcium balance, vitamin D deficiency, and secondary hyperparathyroidism. Consequently, patients are prone to bone demineralization, with diminished bone strength, and are thus prone to fractures that substantially worsen morbid outcomes in this population. However, intra- and interdialytic positive calcium mass balance creates complications of a different kind, which include the occurrence of vascular and cardiac disease and reduced survival. This review aims to shed light on the mechanisms of and relationships between external calcium mass balance and internal calcium redistribution and their consequences. It also discusses the potential to improve current regimens by means of diffusive and convective calcium mass transfer for the achievement of neutral calcium mass balance.