Abstract
Background
Hemodialysis is a life-saving technology used during periods of acute or chronic kidney failure to remove toxins, and maintain fluid, electrolyte and metabolic balance. While this technology plays an important role for pediatric patients with kidney dysfunction, it can alter the pharmacokinetic behavior of medications placing patients at risk for suboptimal dosing and drug toxicity. The ability to directly translate pharmacokinetic alterations into dosing recommendations has thus far been limited and dosing guidance specific to pediatric hemodialysis patients is rare. Despite differences in dialysis prescription and patient populations, intermittent (iHD) and continuous kidney replacement therapy (CKRT) patients are often pooled together. In order to develop evidence-based dosing guidelines, it is important to first prioritize drugs for study in each modality.
Methods
Here we aim to identify priority drugs in two hemodialysis modalities, through: 1) Identification of hospitalized, pediatric patients who received CKRT or intermittent hemodialysis (iHD) using a machine learning-based predictive model based on medications; 2) Identification of medication administration patterns in these patient cohorts; and 3) Identification of the most commonly prescribed drugs that lack published dosing guidance.
Results
Notable differences were found in the pattern of medications and drug dosing guidance between iHD and CKRT patients. Antibiotics, diuretics and sedatives were more common in CKRT patients. Out of the 50 most commonly administered medications in the two modalities, only 34% and 28% had dosing guidance present for iHD and CKRT, respectively.
Conclusions
Our results add to the understanding of the differences between iHD and CKRT patient populations by identifying commonly used medications that lack dosing guidance for each hemodialysis modality, helping to pinpoint priority medications for further study. Overall, this study provides an overview of the current limitations in medication use in this at-risk population, and provides a framework for future studies by identifying commonly used medications in pediatric CKRT and iHD patients.
Graphical abstract
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Data availability
All medication based data generated or analyzed during this study are included in this published article and its supplementary information files. Additional datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
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Acknowledgements
The authors would like to thank the TriNetX team for guidance and technical support.
Funding
This work was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD097775, R21HD104412), the National Heart, Lung, and Blood Institute (2T32HL105321), the University of Utah College of Pharmacy Donald R. Gehlert Fellowship, the American Foundation for Pharmaceutical Education Pre-Doctoral Research Fellowship in Pharmaceutical Sciences and the National Institute of Diabetes and Digestive and Kidney Diseases (F31DK130542).
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467_2023_6199_MOESM5_ESM.tiff
Cumulative unique drug exposure by age group across 30 dialysis days. Blue triangles and red dots represent individual CKRT and iHD patients, respectively. The darker the color, the more patients represented by that symbol. The blue (CKRT) and (iHD) red lines represents the median cumulative number of unique medications across dialysis days. Curves were fit to each modality group using a generalized additive model to highlight trends in drug exposure across dialysis days (TIFF 16.4 MB)
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McKnite, A.M., Green, D.J., Nelson, R. et al. Medication patterns and dosing guidance in pediatric patients supported with intermittent hemodialysis or continuous kidney replacement therapy. Pediatr Nephrol 39, 1521–1532 (2024). https://doi.org/10.1007/s00467-023-06199-z
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DOI: https://doi.org/10.1007/s00467-023-06199-z