The Microbiome and p-Inulin in Hemodialysis: A Feasibility Study

Dominic S. Raj; Michael B. Sohn; David M. Charytan; Jonathan Himmelfarb; T. Alp Ikizler; Rajnish Mehrotra; Ali Ramezani; Renu Regunathan-Shenk; Jesse Y. Hsu; J. Richard Landis; Hongzhe Li; Paul L. Kimmel; Alan S. Kliger; Laura M. Dember; Alan Kliger; David M. Charytan; Emily Robinson; Mark Williams; Daniel E. Weiner; Finnian Mc Causland; Sushrut Waikar; Ezra Aurien-Blajeni; Angeles Cinelli; Tayyaba Nisam; Sookyung Rim; Paul Seok; Caroline Smith; Jasmine Rollins; Dominic Raj; Renu Regunathan-Shenk; Shailendra Sharma; Ali Ramezani; Sarah Andrews; Michelle Dumadag; Christina Franco; Maria Wing; Jonathan Himmelfarb; Rajnish Mehrotra; Lisa Anderson; Lori Linke; Linda Manahan; T. Alp Ikizler; Adriana Hung; Kerri Cavanaugh; Cindy Booker; Brigitte Brannon; Adrienne Clagett; Charles Ellis; Laura M. Dember; J. Richard Landis; Amanda Anderson; Jesse Hsu; Denise Cifelli; Shawn Ballard; Marie Durborow; Tamara Howard; Natalie Kuzla; Lisa Nessel; Ann Tierney; Hicham Skali; Scott Solomon; Aria Rad; Marcelo Di Carli; Masha Gaber; Courtney Foster; Paul Kimmel; John Kusek; Kevin Abbott; Paul Palevsky; Stuart Goldstein; Patricia Hibberd; George Kaysen; Joshua Korzenik; Joao Lima; Allen Nissenson; Vasan Ramachandran; David Raboussin; Jeffrey Siegel; Nosratola Vaziri; Gloria Vigliani; Janet Wittes

doi:10.34067/KID.0006132020

The Microbiome and p-Inulin in Hemodialysis: A Feasibility Study

Dominic S. Raj, Michael B. Sohn, David M. Charytan, Jonathan Himmelfarb, T. Alp Ikizler, Rajnish Mehrotra, Ali Ramezani, Renu Regunathan-Shenk, Jesse Y. Hsu, J. Richard Landis, Hongzhe Li, Paul L. Kimmel, Alan S. Kliger, Laura M. Dember, Alan Kliger, David M. Charytan, Emily Robinson, Mark Williams, Daniel E. Weiner, Finnian Mc CauslandSushrut Waikar, Ezra Aurien-Blajeni, Angeles Cinelli, Tayyaba Nisam, Sookyung Rim, Paul Seok, Caroline Smith, Jasmine Rollins, Dominic Raj, Renu Regunathan-Shenk, Shailendra Sharma, Ali Ramezani, Sarah Andrews, Michelle Dumadag, Christina Franco, Maria Wing, Jonathan Himmelfarb, Rajnish Mehrotra, Lisa Anderson, Lori Linke, Linda Manahan, T. Alp Ikizler, Adriana Hung, Kerri Cavanaugh, Cindy Booker, Brigitte Brannon, Adrienne Clagett, Charles Ellis, Laura M. Dember, J. Richard Landis, Amanda Anderson, Jesse Hsu, Denise Cifelli, Shawn Ballard, Marie Durborow, Tamara Howard, Natalie Kuzla, Lisa Nessel, Ann Tierney, Hicham Skali, Scott Solomon, Aria Rad, Marcelo Di Carli, Masha Gaber, Courtney Foster, Paul Kimmel, John Kusek, Kevin Abbott, Paul Palevsky, Stuart Goldstein, Patricia Hibberd, George Kaysen, Joshua Korzenik, Joao Lima, Allen Nissenson, Vasan Ramachandran, David Raboussin, Jeffrey Siegel, Nosratola Vaziri, Gloria Vigliani, Janet Wittes

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

Abstract

Background The intestinal microbiome is an appealing target for interventions in ESKD because of its likely contribution to uremic toxicity. Before conducting clinical trials of microbiome-altering treatments, it is necessary to understand the within-person and between-person variability in the composition and function of the gut microbiome in patients with ESKD. Methods We conducted a multicenter, nonrandomized, crossover feasibility study of patients on maintenance hemodialysis consisting of three phases: pretreatment (8 weeks); treatment, during which the prebiotic, p-inulin, was administered at a dosage of 8 g twice daily (12 weeks); and post-treatment (8 weeks). Stool samples were collected 1-2 times per week and blood was collected weekly for 28 weeks. The gut microbiome was characterized using 16S ribosomal-RNA sequencing and metabolomic profiling. Results A total of 11 of the 13 participants completed the 28-week study. Interparticipant variability was greater than intraparticipant variability for microbiome composition (P<0.001 by UniFrac distances) and metabolomic composition (P<0.001 by Euclidean distances). p-Inulin was well tolerated by 12 of 13 participants. Adherence to the frequent sample collection and self-aliquoting of stool samples were both 96%. A change in the microbiome composition from pretreatment to post-treatment was evident by the overall shifts in weighted UniFrac distances (P0.004) and a progressive decrease in prevalence of high intraclass correlations, indicating an increase in intraparticipant microbiome diversity during and after p-inulin treatment. An effect of p-inulin on the metabolomic profile was not evident. Conclusions The intraparticipant stability of the gut microbiome under no-treatment conditions, the tolerability of p-inulin, the signals of increased diversity of the microbiome with p-inulin treatment, and the willingness of participants to provide stool samples all support the feasibility of a larger trial to investigate interventions targeting the gut microbiome in patients with ESKD. Whether or not p-inulin has sufficient efficacy as an intervention requires evaluation in larger studies.

Original language	English (US)
Pages (from-to)	445-455
Number of pages	11
Journal	Kidney360
Volume	2
Issue number	3
DOIs	https://doi.org/10.34067/KID.0006132020
State	Published - Mar 1 2021
Externally published	Yes

Keywords

crossover trial
dialysis
feasibility studies
hemodialysis
microbiome
p-inulin-5.
prebiotic

ASJC Scopus subject areas

Nephrology
Medicine (miscellaneous)

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10.34067/KID.0006132020

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Raj, D. S., Sohn, M. B., Charytan, D. M., Himmelfarb, J., Ikizler, T. A., Mehrotra, R., Ramezani, A., Regunathan-Shenk, R., Hsu, J. Y., Landis, J. R., Li, H., Kimmel, P. L., Kliger, A. S., Dember, L. M., Kliger, A., Charytan, D. M., Robinson, E., Williams, M., Weiner, D. E., ... Wittes, J. (2021). The Microbiome and p-Inulin in Hemodialysis: A Feasibility Study. Kidney360, 2(3), 445-455. https://doi.org/10.34067/KID.0006132020

Raj, DS, Sohn, MB, Charytan, DM, Himmelfarb, J, Ikizler, TA, Mehrotra, R, Ramezani, A, Regunathan-Shenk, R, Hsu, JY, Landis, JR, Li, H, Kimmel, PL, Kliger, AS, Dember, LM, Kliger, A, Charytan, DM, Robinson, E, Williams, M, Weiner, DE, Mc Causland, F, Waikar, S, Aurien-Blajeni, E, Cinelli, A, Nisam, T, Rim, S, Seok, P, Smith, C, Rollins, J, Raj, D, Regunathan-Shenk, R, Sharma, S, Ramezani, A, Andrews, S, Dumadag, M, Franco, C, Wing, M, Himmelfarb, J, Mehrotra, R, Anderson, L, Linke, L, Manahan, L, Ikizler, TA, Hung, A, Cavanaugh, K, Booker, C, Brannon, B, Clagett, A, Ellis, C, Dember, LM, Landis, JR, Anderson, A, Hsu, J, Cifelli, D, Ballard, S, Durborow, M, Howard, T, Kuzla, N, Nessel, L, Tierney, A, Skali, H, Solomon, S, Rad, A, Di Carli, M, Gaber, M, Foster, C, Kimmel, P, Kusek, J, Abbott, K, Palevsky, P, Goldstein, S, Hibberd, P, Kaysen, G, Korzenik, J, Lima, J, Nissenson, A, Ramachandran, V, Raboussin, D, Siegel, J, Vaziri, N, Vigliani, G & Wittes, J 2021, 'The Microbiome and p-Inulin in Hemodialysis: A Feasibility Study', Kidney360, vol. 2, no. 3, pp. 445-455. https://doi.org/10.34067/KID.0006132020

@article{e68ce2fd387443e1944e24833d4b7218,

title = "The Microbiome and p-Inulin in Hemodialysis: A Feasibility Study",

abstract = "Background The intestinal microbiome is an appealing target for interventions in ESKD because of its likely contribution to uremic toxicity. Before conducting clinical trials of microbiome-altering treatments, it is necessary to understand the within-person and between-person variability in the composition and function of the gut microbiome in patients with ESKD. Methods We conducted a multicenter, nonrandomized, crossover feasibility study of patients on maintenance hemodialysis consisting of three phases: pretreatment (8 weeks); treatment, during which the prebiotic, p-inulin, was administered at a dosage of 8 g twice daily (12 weeks); and post-treatment (8 weeks). Stool samples were collected 1-2 times per week and blood was collected weekly for 28 weeks. The gut microbiome was characterized using 16S ribosomal-RNA sequencing and metabolomic profiling. Results A total of 11 of the 13 participants completed the 28-week study. Interparticipant variability was greater than intraparticipant variability for microbiome composition (P<0.001 by UniFrac distances) and metabolomic composition (P<0.001 by Euclidean distances). p-Inulin was well tolerated by 12 of 13 participants. Adherence to the frequent sample collection and self-aliquoting of stool samples were both 96%. A change in the microbiome composition from pretreatment to post-treatment was evident by the overall shifts in weighted UniFrac distances (P0.004) and a progressive decrease in prevalence of high intraclass correlations, indicating an increase in intraparticipant microbiome diversity during and after p-inulin treatment. An effect of p-inulin on the metabolomic profile was not evident. Conclusions The intraparticipant stability of the gut microbiome under no-treatment conditions, the tolerability of p-inulin, the signals of increased diversity of the microbiome with p-inulin treatment, and the willingness of participants to provide stool samples all support the feasibility of a larger trial to investigate interventions targeting the gut microbiome in patients with ESKD. Whether or not p-inulin has sufficient efficacy as an intervention requires evaluation in larger studies.",

keywords = "crossover trial, dialysis, feasibility studies, hemodialysis, microbiome, p-inulin-5., prebiotic",

author = "Raj, {Dominic S.} and Sohn, {Michael B.} and Charytan, {David M.} and Jonathan Himmelfarb and Ikizler, {T. Alp} and Rajnish Mehrotra and Ali Ramezani and Renu Regunathan-Shenk and Hsu, {Jesse Y.} and Landis, {J. Richard} and Hongzhe Li and Kimmel, {Paul L.} and Kliger, {Alan S.} and Dember, {Laura M.} and Alan Kliger and Charytan, {David M.} and Emily Robinson and Mark Williams and Weiner, {Daniel E.} and {Mc Causland}, Finnian and Sushrut Waikar and Ezra Aurien-Blajeni and Angeles Cinelli and Tayyaba Nisam and Sookyung Rim and Paul Seok and Caroline Smith and Jasmine Rollins and Dominic Raj and Renu Regunathan-Shenk and Shailendra Sharma and Ali Ramezani and Sarah Andrews and Michelle Dumadag and Christina Franco and Maria Wing and Jonathan Himmelfarb and Rajnish Mehrotra and Lisa Anderson and Lori Linke and Linda Manahan and Ikizler, {T. Alp} and Adriana Hung and Kerri Cavanaugh and Cindy Booker and Brigitte Brannon and Adrienne Clagett and Charles Ellis and Dember, {Laura M.} and Landis, {J. Richard} and Amanda Anderson and Jesse Hsu and Denise Cifelli and Shawn Ballard and Marie Durborow and Tamara Howard and Natalie Kuzla and Lisa Nessel and Ann Tierney and Hicham Skali and Scott Solomon and Aria Rad and {Di Carli}, Marcelo and Masha Gaber and Courtney Foster and Paul Kimmel and John Kusek and Kevin Abbott and Paul Palevsky and Stuart Goldstein and Patricia Hibberd and George Kaysen and Joshua Korzenik and Joao Lima and Allen Nissenson and Vasan Ramachandran and David Raboussin and Jeffrey Siegel and Nosratola Vaziri and Gloria Vigliani and Janet Wittes",

note = "Publisher Copyright: Copyright {\textcopyright} 2021 by the American Society of Nephrology.",

year = "2021",

month = mar,

day = "1",

doi = "10.34067/KID.0006132020",

language = "English (US)",

volume = "2",

pages = "445--455",

journal = "Kidney360",

issn = "2641-7650",

publisher = "Lippincott Williams and Wilkins",

number = "3",

}

TY - JOUR

T1 - The Microbiome and p-Inulin in Hemodialysis

T2 - A Feasibility Study

AU - Raj, Dominic S.

AU - Sohn, Michael B.

AU - Charytan, David M.

AU - Himmelfarb, Jonathan

AU - Ikizler, T. Alp

AU - Mehrotra, Rajnish

AU - Ramezani, Ali

AU - Regunathan-Shenk, Renu

AU - Hsu, Jesse Y.

AU - Landis, J. Richard

AU - Li, Hongzhe

AU - Kimmel, Paul L.

AU - Kliger, Alan S.

AU - Dember, Laura M.

AU - Kliger, Alan

AU - Charytan, David M.

AU - Robinson, Emily

AU - Williams, Mark

AU - Weiner, Daniel E.

AU - Mc Causland, Finnian

AU - Waikar, Sushrut

AU - Aurien-Blajeni, Ezra

AU - Cinelli, Angeles

AU - Nisam, Tayyaba

AU - Rim, Sookyung

AU - Seok, Paul

AU - Smith, Caroline

AU - Rollins, Jasmine

AU - Raj, Dominic

AU - Regunathan-Shenk, Renu

AU - Sharma, Shailendra

AU - Ramezani, Ali

AU - Andrews, Sarah

AU - Dumadag, Michelle

AU - Franco, Christina

AU - Wing, Maria

AU - Himmelfarb, Jonathan

AU - Mehrotra, Rajnish

AU - Anderson, Lisa

AU - Linke, Lori

AU - Manahan, Linda

AU - Ikizler, T. Alp

AU - Hung, Adriana

AU - Cavanaugh, Kerri

AU - Booker, Cindy

AU - Brannon, Brigitte

AU - Clagett, Adrienne

AU - Ellis, Charles

AU - Dember, Laura M.

AU - Landis, J. Richard

AU - Anderson, Amanda

AU - Hsu, Jesse

AU - Cifelli, Denise

AU - Ballard, Shawn

AU - Durborow, Marie

AU - Howard, Tamara

AU - Kuzla, Natalie

AU - Nessel, Lisa

AU - Tierney, Ann

AU - Skali, Hicham

AU - Solomon, Scott

AU - Rad, Aria

AU - Di Carli, Marcelo

AU - Gaber, Masha

AU - Foster, Courtney

AU - Kimmel, Paul

AU - Kusek, John

AU - Abbott, Kevin

AU - Palevsky, Paul

AU - Goldstein, Stuart

AU - Hibberd, Patricia

AU - Kaysen, George

AU - Korzenik, Joshua

AU - Lima, Joao

AU - Nissenson, Allen

AU - Ramachandran, Vasan

AU - Raboussin, David

AU - Siegel, Jeffrey

AU - Vaziri, Nosratola

AU - Vigliani, Gloria

AU - Wittes, Janet

PY - 2021/3/1

Y1 - 2021/3/1

N2 - Background The intestinal microbiome is an appealing target for interventions in ESKD because of its likely contribution to uremic toxicity. Before conducting clinical trials of microbiome-altering treatments, it is necessary to understand the within-person and between-person variability in the composition and function of the gut microbiome in patients with ESKD. Methods We conducted a multicenter, nonrandomized, crossover feasibility study of patients on maintenance hemodialysis consisting of three phases: pretreatment (8 weeks); treatment, during which the prebiotic, p-inulin, was administered at a dosage of 8 g twice daily (12 weeks); and post-treatment (8 weeks). Stool samples were collected 1-2 times per week and blood was collected weekly for 28 weeks. The gut microbiome was characterized using 16S ribosomal-RNA sequencing and metabolomic profiling. Results A total of 11 of the 13 participants completed the 28-week study. Interparticipant variability was greater than intraparticipant variability for microbiome composition (P<0.001 by UniFrac distances) and metabolomic composition (P<0.001 by Euclidean distances). p-Inulin was well tolerated by 12 of 13 participants. Adherence to the frequent sample collection and self-aliquoting of stool samples were both 96%. A change in the microbiome composition from pretreatment to post-treatment was evident by the overall shifts in weighted UniFrac distances (P0.004) and a progressive decrease in prevalence of high intraclass correlations, indicating an increase in intraparticipant microbiome diversity during and after p-inulin treatment. An effect of p-inulin on the metabolomic profile was not evident. Conclusions The intraparticipant stability of the gut microbiome under no-treatment conditions, the tolerability of p-inulin, the signals of increased diversity of the microbiome with p-inulin treatment, and the willingness of participants to provide stool samples all support the feasibility of a larger trial to investigate interventions targeting the gut microbiome in patients with ESKD. Whether or not p-inulin has sufficient efficacy as an intervention requires evaluation in larger studies.

AB - Background The intestinal microbiome is an appealing target for interventions in ESKD because of its likely contribution to uremic toxicity. Before conducting clinical trials of microbiome-altering treatments, it is necessary to understand the within-person and between-person variability in the composition and function of the gut microbiome in patients with ESKD. Methods We conducted a multicenter, nonrandomized, crossover feasibility study of patients on maintenance hemodialysis consisting of three phases: pretreatment (8 weeks); treatment, during which the prebiotic, p-inulin, was administered at a dosage of 8 g twice daily (12 weeks); and post-treatment (8 weeks). Stool samples were collected 1-2 times per week and blood was collected weekly for 28 weeks. The gut microbiome was characterized using 16S ribosomal-RNA sequencing and metabolomic profiling. Results A total of 11 of the 13 participants completed the 28-week study. Interparticipant variability was greater than intraparticipant variability for microbiome composition (P<0.001 by UniFrac distances) and metabolomic composition (P<0.001 by Euclidean distances). p-Inulin was well tolerated by 12 of 13 participants. Adherence to the frequent sample collection and self-aliquoting of stool samples were both 96%. A change in the microbiome composition from pretreatment to post-treatment was evident by the overall shifts in weighted UniFrac distances (P0.004) and a progressive decrease in prevalence of high intraclass correlations, indicating an increase in intraparticipant microbiome diversity during and after p-inulin treatment. An effect of p-inulin on the metabolomic profile was not evident. Conclusions The intraparticipant stability of the gut microbiome under no-treatment conditions, the tolerability of p-inulin, the signals of increased diversity of the microbiome with p-inulin treatment, and the willingness of participants to provide stool samples all support the feasibility of a larger trial to investigate interventions targeting the gut microbiome in patients with ESKD. Whether or not p-inulin has sufficient efficacy as an intervention requires evaluation in larger studies.

KW - crossover trial

KW - dialysis

KW - feasibility studies

KW - hemodialysis

KW - microbiome

KW - p-inulin-5.

KW - prebiotic

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DO - 10.34067/KID.0006132020

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JO - Kidney360

JF - Kidney360

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ER -

The Microbiome and p-Inulin in Hemodialysis: A Feasibility Study

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