Plasma Metabolomics of Dietary Intake of Protein-Rich Foods and Kidney Disease Progression in Children

Xuyuehe Ren, Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
Jingsha Chen, Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
Alison G. Abraham, Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; Department of Epidemiology, University of Colorado School of Public Health, Aurora, Colorado.
Yunwen Xu, Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
Aisha Siewe, Division of Cardiology, Department of Medicine, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
Bradley A. Warady, Department of Pediatrics, University of Missouri-Kansas City School of Medicine, Children's Mercy Kansas City, Kansas City, Missouri.
Paul L. Kimmel, Division of Kidney, Urologic, and Hematologic Diseases, National Institute of Diabetes, Digestive, and Kidney Disorders, National Institutes of Health, Bethesda, Maryland; Division of Renal Diseases and Hypertension, Department of Medicine, George Washington University Medical Center, Washington, District of Columbia.
Ramachandran S. Vasan, University of Texas School of Public Health San Antonio, San Antonio, Texas.
Eugene P. Rhee, Nephrology Division and Endocrinology Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts.
Susan L. Furth, Division of Nephrology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania; Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania; Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
Josef Coresh, Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
Michelle Denburg, Division of Nephrology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania; Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania; Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania; Center for Pediatric Clinical Effectiveness, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Casey M. Rebholz, Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland. Electronic address: crebhol1@jhu.edu.

Document Type

Journal Article

Publication Date

11-8-2023

Journal

Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation

DOI

10.1053/j.jrn.2023.10.007

Keywords

children; chronic kidney disease; dietary intake; protein; red meat

Abstract

OBJECTIVE: Evidence regarding the efficacy of a low-protein diet for patients with CKD is inconsistent and recommending a low-protein diet for pediatric patients is controversial. There is also a lack of objective biomarkers of dietary intake. The purpose of this study was to identify plasma metabolites associated with dietary intake of protein and to assess whether protein-related metabolites are associated with CKD progression. METHODS: Nontargeted metabolomics was conducted in plasma samples from 484 Chronic Kidney Disease in Children (CKiD) participants. Multivariable linear regression estimated the cross-sectional association between 949 known, nondrug metabolites and dietary intake of total protein, animal protein, plant protein, chicken, dairy, nuts and beans, red and processed meat, fish, and eggs, adjusting for demographic, clinical, and dietary covariates. Cox proportional hazards models assessed the prospective association between protein-related metabolites and CKD progression defined as the initiation of kidney replacement therapy or 50% eGFR reduction, adjusting for demographic and clinical covariates. RESULTS: One hundred and twenty-seven (26%) children experienced CKD progression during 5 years of follow-up. Sixty metabolites were significantly associated with dietary protein intake. Among the 60 metabolites, 10 metabolites were significantly associated with CKD progression (animal protein: n = 1, dairy: n = 7, red and processed meat: n = 2, nuts and beans: n = 1), including one amino acid, one cofactor and vitamin, 4 lipids, 2 nucleotides, one peptide, and one xenobiotic. 1-(1-enyl-palmitoyl)-2-oleoyl-glycerophosphoethanolamine (GPE, P-16:0/18:1) was positively associated with dietary intake of red and processed meat, and a doubling of its abundance was associated with 88% higher risk of CKD progression. 3-ureidopropionate was inversely associated with dietary intake of red and processed meat, and a doubling of its abundance was associated with 48% lower risk of CKD progression. CONCLUSIONS: Untargeted plasma metabolomic profiling revealed metabolites associated with dietary intake of protein and CKD progression in a pediatric population.

Department

Medicine

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