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Tacrolimus is widely reported to display diurnal variation in pharmacokinetic parameters with twice‐daily dosing. However, the contribution of chronopharmacokinetics versus food intake is unclear, with even less evidence in the pediatric population. The objectives of this study were to summarize the existing literature by meta‐analysis and evaluate the impact of food composition on 24‐hour pharmacokinetics in pediatric kidney transplant recipients. For the meta‐analysis, 10 studies involving 253 individuals were included. The pooled effect sizes demonstrated significant differences in area under the concentration–time curve from time 0 to 12 hours (standardized mean difference [SMD], 0.27; 95% confidence interval [CI], 0.03‐0.52) and maximum concentration (SMD, 0.75; 95% CI, 0.35‐1.15) between morning and evening dose administration. However, there was significant between‐study heterogeneity that was explained by food exposure. The effect size for minimum concentration was not significantly different overall (SMD, −0.09; 95% CI, −0.27 to 0.09) or across the food exposure subgroups. A 2‐compartment model with a lag time, linear clearance, and first‐order absorption best characterized the tacrolimus pharmacokinetics in pediatric participants. As expected, adding the time of administration and food composition covariates reduced the unexplained within‐subject variability for the first‐order absorption rate constant, but only caloric composition significantly reduced variability for lag time. The available data suggest food intake is the major driver of diurnal variation in tacrolimus exposure, but the associated changes are not reflected by trough concentrations alone. [ABSTRACT FROM AUTHOR]

Background: The process of transition to adult‐based care encompasses a critical period in the life of an adolescent and young adult living with a chronic illness and one that comes with an increase in the risk of poor health outcomes. As yet, there is a dearth of empirical data to help optimize this process to ensure the best long‐term outcome. Methods: This study used a principal components analysis to determine specific constructs measured by a revised version of the transition readiness survey used in our clinic. We investigated changes in these constructs over time. We further investigated the relationship between the change in these constructs over time spent in a focused transition program with adherence. Results: The primary component underlying our transition readiness survey for patients and parents represented self‐efficacy. Time spent in the transition program was an independent predictor of change in self‐efficacy (rho 0.299, p =.015); however, the magnitude of that change had no relationship to adherence. Change in parent‐proxy self‐efficacy was found to have a statistically significant relationship with tacrolimus standard deviation (rho −0.301, p =.026). There was disagreement identified between patient and parent responses on the survey. Neither change in patient nor parent reports of self‐efficacy was found to have a relationship with post‐transfer adherence. Conclusions: This study reaches the novel conclusion that self‐efficacy and parent‐proxy self‐efficacy are dynamic concepts that change over time spent in a focused transition program. The patient‐parent disagreement and the relationship between parent‐proxy self‐efficacy and adherence stress the importance of involving parents/guardians in the transition process as well. [ABSTRACT FROM AUTHOR]

Background: Mitochondrial hepatopathies (MHs) are primary mitochondrial genetic disorders that can present as childhood liver disease. No recognized biomarkers discriminate MH from other childhood liver diseases. The protein biomarkers growth differentiation factor 15 (GDF15) and fibroblast growth factor 21 (FGF21) differentiate mitochondrial myopathies from other myopathies. We evaluated these biomarkers to determine if they discriminate MH from other liver diseases in children., Methods: Serum biomarkers were measured in 36 children with MH (17 had a genetic diagnosis); 38 each with biliary atresia, α1-antitrypsin deficiency, and Alagille syndrome; 20 with NASH; and 186 controls., Results: GDF15 levels compared to controls were mildly elevated in patients with α1-antitrypsin deficiency, Alagille syndrome, and biliary atresia-young subgroup, but markedly elevated in MH (p<0.001). FGF21 levels were mildly elevated in NASH and markedly elevated in MH (p<0.001). Both biomarkers were higher in patients with MH with a known genetic cause but were similar in acute and chronic presentations. Both markers had a strong performance to identify MH with a molecular diagnosis with the AUC for GDF15 0.93±0.04 and for FGF21 0.90±0.06. Simultaneous elevation of both markers >98th percentile of controls identified genetically confirmed MH with a sensitivity of 88% and specificity of 96%. In MH, independent predictors of survival without requiring liver transplantation were international normalized ratio and either GDF15 or FGF21 levels, with levels <2000 ng/L predicting survival without liver transplantation (p<0.01)., Conclusions: GDF15 and FGF21 are significantly higher in children with MH compared to other childhood liver diseases and controls and, when combined, were predictive of MH and had prognostic implications., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)