Indoxyl Sulfate Contributes to Impaired Height Velocity in (Pre)School Children

Abstract

IntroductionGrowth failure is considered the most important clinical outcome parameter in childhood chronic kidney disease (CKD). Central in the pathophysiology of growth failure is the presence of a chronic pro-inflammatory state, presumed partly driven by the accumulation of uremic toxins. In this study, we assessed the association between uremic toxin concentrations and height velocity in a longitudinal multicentric prospective pediatric CKD cohort of (pre-)school aged children and children during pubertal stages. MethodsIn a prospective, multicentric observational study, a selection of uremic toxin levels of children (0-18y) with CKD stage 1-5D was assessed every 3 months (max 2 years) along with clinical growth parameters. Linear mixed models with a random slope for age and a random intercept for child were fitted for height (in cm and SDS). A piecewise linear association between age and height was assumed. ResultsData-analysis included data from 560 visits of 81 children (median age 9.4 years; 2/3 male). In (pre-)school aged children (2-12 years), a 10% increase in concurrent indoxyl sulfate (IxS, total) concentration resulted in an estimated mean height velocity decrease of 0.002 SDS/year (p<.05), given that CKD stage, growth hormone, bicarbonate concentration, and dietary protein intake are held constant. No significant association with height velocity was found in children during pubertal stages (>12years). ConclusionsThe present study demonstrated that especially IxS contributes to a lower height velocity in (pre-)school children, while we could not find a role for uremic toxins with height velocity during pubertal stages.