Association of Dietary Micronutrient Intake and the Metabolome in Children with CKD

Abstract

Key Points:

1. Given the role of diet in kids and micronutrients as cofactors, dietary micronutrient intake and its effect on the metabolome merit further study.

2. Many children with CKD have intake below dietary reference intake of at least one micronutrient despite normal body mass index.

3. Dietary intake of vitamins D and B12 had the greatest associations with plasma metabolites, particularly belonging to lipid pathways.

Background: Children with CKD experience poor growth and development through multiple mechanisms. We aimed to describe deficiencies in dietary micronutrient intake and associate dietary micronutrient intake with metabolic pathways.

Methods: The CKD in Children cohort study enrolled participants 6 months to 16 years with CKD stages 2–4 across North America. Micronutrient intake (three trace minerals, eight water-soluble vitamins, and four fat-soluble vitamins) was quantified by food frequency questionnaires at 6-month, 2-year and 4-year visits. Blood was collected at those time points for untargeted metabolomic profiling. Associations between 990 plasma metabolite features and dietary micronutrient intake were quantified with multiple linear regression using mixed effects regression models.

Results: There were 575 participants with available data at the 6-month visit (mean age 12 years, 39% female, eGFR 53 ml/min per 1.73 m², body mass index Z-score 0.7). The most common deficiency of micronutrient intake was vitamin D (90% of participants), followed by vitamin E (77%), and more than 45% of participants did not meet the dietary reference intake of iron and folate. Children with lower eGFR had lower intake of zinc and vitamins B5 and B6. Micronutrient intake was associated with 99 total and 42 unique metabolites. Dietary intake of vitamins D and B12 was associated with many metabolites involved in lipid superpathways and phosphatidylcholine, plasmalogen, and lysophospholipid subpathways. Dietary intake of iron, folate, and vitamins C, A, and K was associated with metabolites primarily belonging to the xenobiotic, cofactor/vitamin, and amino acid superpathways. The strongest associations between dietary micronutrient intake and plasma metabolites were between intake of vitamin C with stachydrine and 3-hydroxystachydrine.

Conclusions: Most children with CKD have intake below dietary reference intake of at least one micronutrient despite normal body mass index, which was associated with alterations in lipid metabolism.

Clinical Trial registry name and registration number:: The validation cohort, “Vitamin D Supplementation in Glomerular Disease (D-FINE),” was registered with clinicaltrials.gov, NCT01835639.

Keywords: CKD nondialysis; metabolomics; mineral metabolism; nutrition; pediatric nephrology; vitamin B1; vitamin C; vitamin D.