Metabolomic Patterns in Adolescents With Mild to Moderate CKD

Abstract

To the Editor: Metabolomics of patients with chronic kidney disease (CKD) can provide a unique perspective on subclinical metabolic perturbations relative to the glomerular filtration rate (GFR) because the kidneys have a major role in maintaining metabolic homeostasis. Examination of metabolomics in CKD has largely focused on adults in advanced stages and centered on risk of mortality. However, metabolic alterations in children and adolescents with mild-moderate CKD presents a significant risk of secondary morbidities because they are undergoing periods of rapid growth and development and would otherwise not normally experience untoward issues with nutrient catabolism. The goal of this study was to use targeted metabolomics to identify altered biochemical pathways in adolescents with mild to moderate CKD (stages 2 and 3b) in 2 cohorts matched by age, gender, and CKD etiology. Metabolites and their ratios were selected a priori due to previously documented alterations in CKD. For this investigation, CKD etiology was categorized as glomerulopathy (G) or nonglomerular urologic anomalies (NG), the latter of which is defined as congenital abnormalities of the kidney and urinary tract and includes the largest proportion of the pediatric CKD population. Therefore, the 2 cohorts (CKD-2 and -3b) had equal numbers with G and NG. Forty plasma specimens and data, including directly measured GFR (mGFR, determined by plasma iohexol clearance) were selected from a large heterogeneous population of children and adolescents in the ongoing, prospective, observational Chronic Kidney Disease in Children (CKiD) study in North America. By closely matching the cohorts, an unbiased approach to the metabolomics of mild to moderate CKD was achieved. We posited that abnormal metabolic findings would be present in early (mild) CKD (stage 2), with some significant differences observed between CKD stages 2 and 3b (moderate).