Application of Individualized Bayesian Urea Kinetic Modeling to Pediatric Hemodialysis

Abstract

Incorporating urea rebound using equilibrated urea concentration (Ceq) after hemodialysis (HD) is essential for accurate assessment of HD efficiency. It is impractical to measure Ceq in clinical settings, and there are no recommended methodologies to predict Ceq in children. The objective of this work is to assess the ability of an Individualized Bayesian Urea Kinetic Model (IBKM) for predicting Ceq in children receiving HD. Developed based on adult HD data, the IBKM is a two-pool urea kinetic model that calculates Bayesian estimates of individual Ceq. Blood urea nitrogen (BUN) samples from 30 HD sessions in 13 children (age 12-18 years) were taken at pre-HD, immediately post-HD, and 60 minutes post-HD (Ceq). The IBKM and estimated population parameters from adult data were fitted to the observed data from children to predict individual Ceq using NONMEM VI software in comparison with observed Ceq (9.5 +/- 3.8 mmol/L), the average individual predicted Ceq was 9.4 +/- 3.8 mmol/L, with absolute individual prediction error of 6.2% +/- 4.4%. For a given dialysis goal and desired dialysis duration, the required blood flow rate and dialyzer size are predicted by IBKM and confirmed by the analysis data. This study suggests that the IBKM can be used in a pediatric HD setting and accurately predict Ceq in children using only pre-HD and immediately post-HD BUN.

Effect of Kidney Function on Drug Kinetics and Dosing in Neonates, Infants, and Children

“…Pharmacometric approaches can be leveraged to identify predictive covariates, characterize exposure/response and TW of drugs, and provide a scientific basis for individualized dosing strategies, including Bayesian-based TDM, in neonates, infants, and children [ 242 – 245 , 289 , 295 , 296 ]. Model-based approaches can also be applied to fine-tune RRT strategies in pediatric patients [ 296 – 298 ].…”

Understanding Renal Replacement Therapy and Dosing of Drugs in Pediatric Patients with Kidney Disease

“…Although research in this area is difficult and complicated by variability in clinical practice and the complexity of diverse critical illnesses, new further research is warranted to allow for pediatric‐focused dosing guidance for children with renal failure. For example, in a recent publication titled “Application of Individualized Bayesian Urea Kinetic Modeling to Pediatric Hemodialysis,” 27 advanced modeling and simulation techniques were used to create an individualized Bayesian urea kinetic model (IBKM) that can predict equilibrated urea concentration (Ceq) after hemodialysis based on BUN samples taken prior to and immediately after the hemodialysis sessions. The average individual predicted Ceq was 9.4 ± 3.8 mmol/L, in comparison to the observed Ceq of 9.5 ± 3.8 mmol/L, with an absolute individual prediction error of 6.2% ± 4.4%.…”

Optimizing Drug Development and Use in Patients With Kidney Disease

“…16,17 However, there is very limited information in the literature that clearly guides their use. Recent data show that drugdosing studies have been conducted for fewer than 20% and 1% of currently marketed drugs for use during continuous and hybrid replacement therapies, respectively.…”

“…However, there remains a paucity of current and clinically relevant data for guiding drug 15 There is an increasing number of intermittent (eg, 6 times per week vs 3 times per week), continuous, and hybrid RRT modalities used today to treat adult and pediatric patients with kidney disease. 16,17 However, there is very limited information in the literature that clearly guides their use. Recent data show that drugdosing studies have been conducted for fewer than 20% and 1% of currently marketed drugs for use during continuous and hybrid replacement therapies, respectively.…”

“…Most hemodialysis drug clearance and dosing data that are used presently are based on conventional modalities that in some cases are obsolete 15 . There is an increasing number of intermittent (eg, 6 times per week vs 3 times per week), continuous, and hybrid RRT modalities used today to treat adult and pediatric patients with kidney disease 16 , 17 . However, there is very limited information in the literature that clearly guides their use.…”