Metabolite Biomarkers of CKD Progression in Children.
Adenosine
/ analogs & derivatives
Adolescent
Alanine
/ analogs & derivatives
Biomarkers
/ blood
Child
Citrates
/ blood
Disease Progression
Female
Follow-Up Studies
Glomerular Filtration Rate
Humans
Hydrocortisone
/ analogs & derivatives
Male
Metabolomics
Prospective Studies
Pseudouridine
/ blood
Renal Insufficiency, Chronic
/ blood
Renal Replacement Therapy
Sugar Acids
/ blood
Sulfides
/ blood
Tryptophan
/ analogs & derivatives
Uridine
/ analogs & derivatives
biomarkers
children
chronic kidney disease
metabolism
pediatric nephrology
progression of chronic renal failure
Journal
Clinical journal of the American Society of Nephrology : CJASN
ISSN: 1555-905X
Titre abrégé: Clin J Am Soc Nephrol
Pays: United States
ID NLM: 101271570
Informations de publication
Date de publication:
08 2021
08 2021
Historique:
received:
06
01
2021
accepted:
17
06
2021
entrez:
7
8
2021
pubmed:
8
8
2021
medline:
15
1
2022
Statut:
ppublish
Résumé
Metabolomics facilitates the discovery of biomarkers and potential therapeutic targets for CKD progression. We evaluated an untargeted metabolomics quantification of stored plasma samples from 645 Chronic Kidney Disease in Children (CKiD) participants. Metabolites were standardized and logarithmically transformed. Cox proportional hazards regression examined the association between 825 nondrug metabolites and progression to the composite outcome of KRT or 50% reduction of eGFR, adjusting for age, sex, race, body mass index, hypertension, glomerular versus nonglomerular diagnosis, proteinuria, and baseline eGFR. Stratified analyses were performed within subgroups of glomerular/nonglomerular diagnosis and baseline eGFR. Baseline characteristics were 391 (61%) male; median age 12 years; median eGFR 54 ml/min per 1.73 m Untargeted plasma metabolomic profiling facilitated discovery of novel metabolite associations with CKD progression in children that were independent of established clinical predictors and highlight the role of select biologic pathways.
Sections du résumé
BACKGROUND AND OBJECTIVES
Metabolomics facilitates the discovery of biomarkers and potential therapeutic targets for CKD progression.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS
We evaluated an untargeted metabolomics quantification of stored plasma samples from 645 Chronic Kidney Disease in Children (CKiD) participants. Metabolites were standardized and logarithmically transformed. Cox proportional hazards regression examined the association between 825 nondrug metabolites and progression to the composite outcome of KRT or 50% reduction of eGFR, adjusting for age, sex, race, body mass index, hypertension, glomerular versus nonglomerular diagnosis, proteinuria, and baseline eGFR. Stratified analyses were performed within subgroups of glomerular/nonglomerular diagnosis and baseline eGFR.
RESULTS
Baseline characteristics were 391 (61%) male; median age 12 years; median eGFR 54 ml/min per 1.73 m
CONCLUSIONS
Untargeted plasma metabolomic profiling facilitated discovery of novel metabolite associations with CKD progression in children that were independent of established clinical predictors and highlight the role of select biologic pathways.
Identifiants
pubmed: 34362785
pii: 01277230-202108000-00009
doi: 10.2215/CJN.00220121
pmc: PMC8455058
doi:
Substances chimiques
Biomarkers
0
C-glycosyltryptophan
0
Citrates
0
Sugar Acids
0
Sulfides
0
cortisol 21-sulfate
1253-43-6
Pseudouridine
1445-07-4
gulonic acid
20246-33-7
N(6)-(N-threonylcarbonyl)adenosine
24719-82-2
5,6-dihydrouridine
5627-05-4
2-methylcitric acid
6061-96-7
Tryptophan
8DUH1N11BX
lanthionine
JO78O46X3K
Adenosine
K72T3FS567
Alanine
OF5P57N2ZX
Uridine
WHI7HQ7H85
Hydrocortisone
WI4X0X7BPJ
Types de publication
Journal Article
Multicenter Study
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1178-1189Subventions
Organisme : NIDDK NIH HHS
ID : U01 DK066143
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK066174
Pays : United States
Organisme : NIDDK NIH HHS
ID : U24 DK066116
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK106982
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK103225
Pays : United States
Organisme : NIDDK NIH HHS
ID : K23 DK093556
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK106981
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK085689
Pays : United States
Investigateurs
Vasan S Ramachandran
(VS)
Joseph Massaro
(J)
Clary Clish
(C)
Jeffrey Schelling
(J)
Michelle Denburg
(M)
Susan Furth
(S)
Bradley Warady
(B)
Joseph Bonventre
(J)
Sushrut Waikar
(S)
Gearoid McMahon
(G)
Venkata Sabbisetti
(V)
Josef Coresh
(J)
Morgan Grams
(M)
Casey Rebholz
(C)
Alison Abraham
(A)
Adriene Tin
(A)
Chirag Parikh
(C)
Jon Klein
(J)
Steven Coca
(S)
Bart S Ferket
(BS)
Girish N Nadkarni
(GN)
Eugene Rhee
(E)
Paul L Kimmel
(PL)
Daniel Gossett
(D)
Brad Rovin
(B)
Michael G Shlipak
(MG)
M Sarnak
(M)
Andrew S Levey
(AS)
Lesley A Inker
(LA)
Meredith Foster
(M)
Orlando M Gutiérrez
(OM)
Joachim Ix
(J)
Ruth Dubin
(R)
Jesse Seegmiller
(J)
Tom Hostetter
(T)
Rajat Deo
(R)
Harold I Feldman
(HI)
Amanda Anderson
(A)
Theodore Mifflin
(T)
Dawei Xie
(D)
Haochang Shou
(H)
Shawn Ballard
(S)
Krista Whitehead
(K)
Heather Collins
(H)
Jason Greenberg
(J)
Peter Ganz
(P)
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2021 by the American Society of Nephrology.
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