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Blood Purification

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

Lin-Chun Wang, Leticia M Tapia Silva, Xia Tao, null, Ohnmar Thwin, Hanjie Zhang, Stephan Thijssen, Peter Kotanko, Nadja Grobe

Abstract

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.

About the Contributors

Ohnmar Thwin, MD

Research Scientist

Ohnmar Thwin was born in Yangon, Burma. She received her medical degree from the Institute of Medicine, Yangon, Burma, and her MPH degree from Mahidol University, Bangkok, Thailand. Ohnmar served as a senior health training officer for the nternational Rescue Committee providing chronic disease prevention education, as well as empowering and helping to rebuild the lives of refugees affected by violent conflict and disasters. 

Hanjie Zhang, MSc, PhD

Supervisor of Biostatistics and Applied Artificial Intelligence /Machine Learning

Hanjie joined RRI in 2014. She received a master’s degree in statistics from Columbia University, New York, and a PhD in medical science from the University of Maastricht, The Netherlands. Hanjie has been involved in the design of several large cluster-randomized clinical trials and complex statistical analyses in collaboration with the Medical Office, FMCNA...

Stephan Thijssen, MD

Vice President, Applied and Basic Research

Prior to coming to New York, Stephan worked in the Nephrology Department at the University Hospital Homburg, Germany. He joined RRI in 2005. Stephan brings more than one and a half decades of research experience to the RRI team, covering laboratory research, clinical research, epidemiology research, and mathematical modeling.

Dr. Peter Kotanko, MD

RRI Research Director

SVP, Corporate Research & Development

Peter Kotanko, MD, is Research Director at the Renal Research Institute (RRI), New York. Prior to joining RRI, from 1997 to 2007 he served as vice chair of a department of internal medicine at an academic teaching hospital in Graz, Austria. Prior to moving to Graz in 1989, he worked from 1982 to 1989 in the Department of Physiology and the University Clinic of Internal Medicine in Innsbruck, Austria. From 1995 to 1996 he trained in nephrology at the Hammersmith Hospital, London, United Kingdom.

Nadja Grobe, MS, PhD

Supervisor, Laboratory Research

Nadja received her MS and PhD in biochemistry from the Martin Luther University Halle-Wittenberg, Germany. Prior to joining RRI in 2017, she gained more than 10 years of experience in guiding and implementing chemistry, biochemistry, and biomedical-focused research teams in nonprofit, academia, and government. Her previous research has been funded by the American Heart Association, the National Institutes of Health, and the American Society of Nephrology.

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