Conceptual evaluation of urea rebound in pediatric hemodialysis patients by a physiology-based pharmacokinetic simulation study
V Gotta(1), O Marsenic(2), M Pfister(1)
(1) Pediatric Pharmacology & Pharmacometrics, University of Basel Children’s Hospital, Basel, Switzerland (2) Pediatric Nephrology, Yale-New Have Children’s Hospital and Yale School of Medicine, New Haven, CT
Objectives: Pediatric hemodialysis (HD) dosing and monitoring strategies are mainly derived from adult studies, based on pre- and post-HD urea plasma concentration sampling. Accuracy of such HD evaluation approach depends on extent and duration of post-HD urea rebound, which occurs due to redistribution of urea from slowly perfused (peripheral) to quickly perfused (central) body compartments. The goal of this urea kinetic simulation study was to evaluate expected urea rebound in paediatric HD patients.
Methods: Realistic pediatric HD prescription parameters and demographics were calculated over body weight (BW)-bands of 5 kg from a large registry database (DaVita) with ≥20 patients and >130 HD sessions per BW-band. Typical urea concentration-time profiles during and after HD sessions were simulated applying published urea kinetic data[1,2] and implementing expected physiologically-based kinetic changes in pediatrics (age-, body weight, and gender-dependency of total body water[3,4], cardiac output[5], and fraction of skeletal muscle mass[6] as indicator of slowly equilibrating somatic tissue mass). Time to regaining equilibrium after HD sessions between central and peripheral urea concentration (TTE) was calculated (i.e. at least 97% of complete equilibrium).
Results: In children up to 25 kg (10 years) predicted TTE was ≤5 min, in adolescents up to 35 kg (17 years) ≤10 min. In young adults (19-21 years, 40-120 kg) TTE was up to 25 min (longest in boys weighing >80 kg), while almost 90% of complete equilibrium was predicted to be achieved 5 min post-HD.
Conclusions: Results from urea kinetic simulations that take HD prescription parameters and physiologic changes in pediatrics into account indicate that time to equilibrium is shorter in pediatric than in adult HD patients, with urea rebound occurring within 5-10 min after HD sessions. This finding can be utilized to design optimal sampling strategies in urea kinetic studies in pediatric HD patients.
References:
[1] Pfister et al. Hemodial. Int. 2008
[2] Odeh et al. Clin. Pharmacol. Ther. 1993
[3] Watson et al. Am. J. Clin. Nutr. 1980
[4] Cheek et al. Am. J. Dis. Child 1966
[5] de Simone et al. Circulation 1997
[6] McCarthy et al. Pediatr. Obes. 2014
