The association between TMAO, CMPF, and clinical outcomes in advanced chronic kidney disease: results from the European QUALity (EQUAL) Study.
3-carboxy-4-methyl-5-propyl-2-furanpropionate
CKD
fish intake
kidney replacement therapy
mortality
red meat
trimethylamine N-oxide
uremic toxins
Journal
The American journal of clinical nutrition
ISSN: 1938-3207
Titre abrégé: Am J Clin Nutr
Pays: United States
ID NLM: 0376027
Informations de publication
Date de publication:
19 12 2022
19 12 2022
Historique:
received:
31
05
2022
revised:
18
08
2022
accepted:
24
09
2022
pubmed:
28
9
2022
medline:
21
12
2022
entrez:
27
9
2022
Statut:
ppublish
Résumé
Trimethylamine N-oxide (TMAO), a metabolite from red meat and fish consumption, plays a role in promoting cardiovascular events. However, data regarding TMAO and its impact on clinical outcomes are inconclusive, possibly due to its undetermined dietary source. We hypothesized that circulating TMAO derived from fish intake might cause less harm compared with red meat sources by examining the concomitant level of 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF), a known biomarker of fish intake, and investigated the association between TMAO, CMPF, and outcomes. Patients were recruited from the European QUALity (EQUAL) Study on treatment in advanced chronic kidney disease among individuals aged ≥65 y whose estimated glomerular filtration rate (eGFR) had dropped for the first time to ≤20 mL/min per 1.73 m2 during the last 6 mo. The association between TMAO, CMPF, and outcomes including all-cause mortality and kidney replacement therapy (KRT) was assessed among 737 patients. Patients were further stratified by median cutoffs of TMAO and CMPF, suggesting high/low red meat and fish intake. During a median of 39 mo of follow-up, 232 patients died. Higher TMAO was independently associated with an increased risk of all-cause mortality (multivariable HR: 1.46; 95% CI: 1.17, 1.83). Higher CMPF was associated with a reduced risk of both all-cause mortality (HR: 0.79; 95% CI: 0.71, 0.89) and KRT (HR: 0.80; 95% CI: 0.71, 0.90), independently of TMAO and other clinically relevant confounders. In comparison to patients with low TMAO and CMPF, patients with low TMAO and high CMPF had reduced risk of all-cause mortality (adjusted HR: 0.49; 95% CI: 0.31, 0.73), whereas those with high TMAO and high CMPF showed no association across adjusted models. High CMPF conferred an independent role in health benefits and might even counteract the unfavorable association between TMAO and outcomes. Whether higher circulating CMPF concentrations are due to fish consumption, and/or if CMPF is a protective factor, remains to be verified.
Sections du résumé
BACKGROUND
Trimethylamine N-oxide (TMAO), a metabolite from red meat and fish consumption, plays a role in promoting cardiovascular events. However, data regarding TMAO and its impact on clinical outcomes are inconclusive, possibly due to its undetermined dietary source.
OBJECTIVES
We hypothesized that circulating TMAO derived from fish intake might cause less harm compared with red meat sources by examining the concomitant level of 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF), a known biomarker of fish intake, and investigated the association between TMAO, CMPF, and outcomes.
METHODS
Patients were recruited from the European QUALity (EQUAL) Study on treatment in advanced chronic kidney disease among individuals aged ≥65 y whose estimated glomerular filtration rate (eGFR) had dropped for the first time to ≤20 mL/min per 1.73 m2 during the last 6 mo. The association between TMAO, CMPF, and outcomes including all-cause mortality and kidney replacement therapy (KRT) was assessed among 737 patients. Patients were further stratified by median cutoffs of TMAO and CMPF, suggesting high/low red meat and fish intake.
RESULTS
During a median of 39 mo of follow-up, 232 patients died. Higher TMAO was independently associated with an increased risk of all-cause mortality (multivariable HR: 1.46; 95% CI: 1.17, 1.83). Higher CMPF was associated with a reduced risk of both all-cause mortality (HR: 0.79; 95% CI: 0.71, 0.89) and KRT (HR: 0.80; 95% CI: 0.71, 0.90), independently of TMAO and other clinically relevant confounders. In comparison to patients with low TMAO and CMPF, patients with low TMAO and high CMPF had reduced risk of all-cause mortality (adjusted HR: 0.49; 95% CI: 0.31, 0.73), whereas those with high TMAO and high CMPF showed no association across adjusted models.
CONCLUSIONS
High CMPF conferred an independent role in health benefits and might even counteract the unfavorable association between TMAO and outcomes. Whether higher circulating CMPF concentrations are due to fish consumption, and/or if CMPF is a protective factor, remains to be verified.
Identifiants
pubmed: 36166845
pii: S0002-9165(23)03715-2
doi: 10.1093/ajcn/nqac278
pmc: PMC9761748
doi:
Substances chimiques
Methylamines
0
trimethyloxamine
FLD0K1SJ1A
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1842-1851Subventions
Organisme : Department of Health
Pays : United Kingdom
Investigateurs
Andreas Schneider
(A)
Anke Torp
(A)
Beate Iwig
(B)
Boris Perras
(B)
Christian Marx
(C)
Christiane Drechsler
(C)
Christof Blaser
(C)
Christoph Wanner
(C)
Claudia Emde
(C)
Detlef Krieter
(D)
Dunja Fuchs
(D)
Ellen Irmler
(E)
Eva Platen
(E)
Hans Schmidt-Gürtler
(H)
Hendrik Schlee
(H)
Holger Naujoks
(H)
Ines Schlee
(I)
Sabine Cäsar
(S)
Joachim Beige
(J)
Jochen Röthele
(J)
Justyna Mazur
(J)
Kai Hahn
(K)
Katja Blouin
(K)
Katrin Neumeier
(K)
Kirsten Anding-Rost
(K)
Lothar Schramm
(L)
Monika Hopf
(M)
Nadja Wuttke
(N)
Nikolaus Frischmuth
(N)
Pawlos Ichtiaris
(P)
Petra Kirste
(P)
Petra Schulz
(P)
Sabine Aign
(S)
Sandra Biribauer
(S)
Sherin Manan
(S)
Silke Röser
(S)
Stefan Heidenreich
(S)
Stephanie Palm
(S)
Susanne Schwedler
(S)
Sylke Delrieux
(S)
Sylvia Renker
(S)
Sylvia Schättel
(S)
Theresa Stephan
(T)
Thomas Schmiedeke
(T)
Thomas Weinreich
(T)
Til Leimbach
(T)
Torsten Stövesand
(T)
Udo Bahner
(U)
Wolfgang Seeger
(W)
Adamasco Cupisti
(A)
Adelia Sagliocca
(A)
Alberto Ferraro
(A)
Alessandra Mele
(A)
Alessandro Naticchia
(A)
Alex Còsaro
(A)
Andrea Ranghino
(A)
Andrea Stucchi
(A)
Angelo Pignataro
(A)
Antonella De Blasio
(A)
Antonello Pani
(A)
Aris Tsalouichos
(A)
Bellasi Antonio
(B)
Biagio Raffaele Di Iorio
(B)
Butti Alessandra
(B)
Cataldo Abaterusso
(C)
Chiara Somma
(C)
Claudia D'Alessandro
(C)
Claudia Torino
(C)
Claudia Zullo
(C)
Claudio Pozzi
(C)
Daniela Bergamo
(D)
Daniele Ciurlino
(D)
Daria Motta
(D)
Domenico Russo
(D)
Enrico Favaro
(E)
Federica Vigotti
(F)
Ferruccio Ansali
(F)
Ferruccio Conte
(F)
Francesca Cianciotta
(F)
Francesca Giacchino
(F)
Francesco Cappellaio
(F)
Francesco Pizzarelli
(F)
Gaetano Greco
(G)
Gaetana Porto
(G)
Giada Bigatti
(G)
Giancarlo Marinangeli
(G)
Gianfranca Cabiddu
(G)
Giordano Fumagalli
(G)
Giorgia Caloro
(G)
Giorgina Piccoli
(G)
Giovanbattista Capasso
(G)
Giovanni Gambaro
(G)
Giuliana Tognarelli
(G)
Giuseppe Bonforte
(G)
Giuseppe Conte
(G)
Giuseppe Toscano
(G)
Goffredo Del Rosso
(G)
Irene Capizzi
(I)
Ivano Baragetti
(I)
Lamberto Oldrizzi
(L)
Loreto Gesualdo
(L)
Luigi Biancone
(L)
Manuela Magnano
(M)
Marco Ricardi
(M)
Maria Di Bari
(M)
Maria Laudato
(M)
Maria Luisa Sirico
(M)
Martina Ferraresi
(M)
Michele Provenzano
(M)
Moreno Malaguti
(M)
Nicola Palmieri
(N)
Paola Murrone
(P)
Pietro Cirillo
(P)
Pietro Dattolo
(P)
Pina Acampora
(P)
Rita Nigro
(R)
Roberto Boero
(R)
Roberto Scarpioni
(R)
Rosa Sicoli
(R)
Rosella Malandra
(R)
Silvana Savoldi
(S)
Silvio Bertoli
(S)
Silvio Borrelli
(S)
Stefania Maxia
(S)
Stefano Maffei
(S)
Stefano Mangano
(S)
Teresa Cicchetti
(T)
Tiziana Rappa
(T)
Valentina Palazzo
(V)
Walter De Simone
(W)
Anita Schrander
(A)
Bastiaan van Dam
(B)
Carl Siegert
(C)
Carlo Gaillard
(C)
Charles Beerenhout
(C)
Cornelis Verburgh
(C)
Cynthia Janmaat
(C)
Ellen Hoogeveen
(E)
Ewout Hoorn
(E)
Friedo Dekker
(F)
Johannes Boots
(J)
Henk Boom
(H)
Jan-Willem Eijgenraam
(JW)
Jeroen Kooman
(J)
Joris Rotmans
(J)
Kitty Jager
(K)
Liffert Vogt
(L)
Maarten Raasveld
(M)
Marc Vervloet
(M)
Marjolijn van Buren
(M)
Merel van Diepen
(M)
Nicholas Chesnaye
(N)
Paul Leurs
(P)
Pauline Voskamp
(P)
Sadie van Esch
(S)
Siska Boorsma
(S)
Stefan Berger
(S)
Constantijn Konings
(C)
Zeynep Aydin
(Z)
Aleksandra Musiała
(A)
Anna Szymczak
(A)
Ewelina Olczyk
(E)
Hanna Augustyniak-Bartosik
(H)
Ilona Miśkowiec-Wiśniewska
(I)
Jacek Manitius
(J)
Joanna Pondel
(J)
Kamila Jędrzejak
(K)
Katarzyna Nowańska
(K)
Łukasz Nowak
(Ł)
Maciej Szymczak
(M)
Magdalena Durlik
(M)
Szyszkowska Dorota
(S)
Teresa Nieszporek
(T)
Zbigniew Heleniak
(Z)
Andreas Jonsson
(A)
Björn Rogland
(B)
Carin Wallquist
(C)
Denes Vargas
(D)
Emöke Dimény
(E)
Fredrik Sundelin
(F)
Fredrik Uhlin
(F)
Gunilla Welander
(G)
Isabel Bascaran Hernandez
(I)
Knut-Christian Gröntoft
(KC)
Maria Stendahl
(M)
Maria Eriksson Svensson
(M)
Marie Evans
(M)
Olof Heimburger
(O)
Pavlos Kashioulis
(P)
Stefan Melander
(S)
Tora Almquist
(T)
Alistair Woodman
(A)
Anna McKeever
(A)
Asad Ullah
(A)
Barbara McLaren
(B)
Camille Harron
(C)
Carla Barrett
(C)
Charlotte O'Toole
(C)
Christina Summersgill
(C)
Colin Geddes
(C)
Deborah Glowski
(D)
Deborah McGlynn
(D)
Dympna Sands
(D)
Fergus Caskey
(F)
Geena Roy
(G)
Gillian Hirst
(G)
Hayley King
(H)
Helen McNally
(H)
Houda Masri-Senghor
(H)
Hugh Murtagh
(H)
Hugh Rayner
(H)
Jane Turner
(J)
Joanne Wilcox
(J)
Jocelyn Berdeprado
(J)
Jonathan Wong
(J)
Joyce Banda
(J)
Kirsteen Jones
(K)
Lesley Haydock
(L)
Lily Wilkinson
(L)
Margaret Carmody
(M)
Maria Weetman
(M)
Martin Joinson
(M)
Mary Dutton
(M)
Michael Matthews
(M)
Neal Morgan
(N)
Nina Bleakley
(N)
Paul Cockwell
(P)
Paul Roderick
(P)
Phil Mason
(P)
Philip Kalra
(P)
Rincy Sajith
(R)
Sally Chapman
(S)
Santee Navjee
(S)
Sarah Crosbie
(S)
Sharon Brown
(S)
Sheila Tickle
(S)
Suresh Mathavakkannan
(S)
Ying Kuan
(Y)
Informations de copyright
© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.
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