Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; Department of Epidemiology, University of Colorado School of Public Health, Aurora, Colorado.
J Ren Nutr. 2024 Mar;34(2):95-104. doi: 10.1053/j.jrn.2023.10.007. Epub 2023 Nov 8.
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.
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.
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.
Untargeted plasma metabolomic profiling revealed metabolites associated with dietary intake of protein and CKD progression in a pediatric population.
关于低蛋白饮食对 CKD 患者疗效的证据不一致，推荐低蛋白饮食用于儿科患者存在争议。此外，还缺乏饮食摄入的客观生物标志物。本研究旨在鉴定与蛋白质饮食摄入相关的血浆代谢物，并评估蛋白质相关代谢物是否与 CKD 进展相关。
对 484 名慢性肾脏病儿童（CKiD）参与者的血浆样本进行非靶向代谢组学分析。多变量线性回归估计了 949 种已知非药物代谢物与总蛋白质、动物蛋白、植物蛋白、鸡肉、乳制品、坚果和豆类、红色和加工肉类、鱼类以及鸡蛋饮食摄入之间的横断面关联，同时调整了人口统计学、临床和饮食协变量。Cox 比例风险模型评估了蛋白质相关代谢物与 CKD 进展（定义为开始肾脏替代治疗或 eGFR 降低 50%）之间的前瞻性关联，同时调整了人口统计学和临床协变量。
在 5 年的随访期间，有 127 名（26%）儿童发生 CKD 进展。127 名（26%）儿童在 5 年的随访期间发生 CKD 进展。有 60 种代谢物与膳食蛋白质摄入显著相关。在这 60 种代谢物中，有 10 种代谢物与 CKD 进展显著相关（动物蛋白：n=1，乳制品：n=7，红色和加工肉类：n=2，坚果和豆类：n=1），包括 1 种氨基酸、1 种辅因子和维生素、4 种脂质、2 种核苷酸、1 种肽和 1 种外源性化合物。1-(1-烯基-棕榈酰基)-2-油酰基甘油磷酸乙醇胺（GPE，P-16:0/18:1）与红色和加工肉类的饮食摄入呈正相关，其丰度增加一倍与 CKD 进展的风险增加 88%相关。3-脲基丙酸与红色和加工肉类的饮食摄入呈负相关，其丰度增加一倍与 CKD 进展的风险降低 48%相关。
非靶向血浆代谢组学分析揭示了与儿科人群蛋白质饮食摄入和 CKD 进展相关的代谢物。
