Understanding Urea Kinetic Factors That Enhance Personalized Hemodialysis Prescription in Children

Urea dialyzer clearance (K-D) has been suggested to be underpredicted from blood flow (Q(B)), dialysate flow (Q(D)), and in vitro mass transfer-area coefficient of urea (KoA) in pediatric hemodialysis (HD) patients using a widely accepted mechanistic equation. We characterize factors that could explain this, assuming that it results from a bias between reported in vitro and actual in vivo KoA. An adult urea kinetic model was scaled to 923 patients aged 1-29 years based on pediatric physiologic knowledge (intercompartmental clearance, volumes of distribution). Using data from 2,676 HD sessions of those patients (pre-/post-HD urea concentrations and HD treatment parameters), mixed effect modeling was applied to estimate individual KoA correction factors (f(KoA)) required for unbiased K-D and post-HD urea concentration predictions in vivo. Q(D)/Q(B) ratio was most strongly associated with individual f(KoA) estimates (P < 0.001; f(KoA) = -1%, 18%, and 110% at Q(D)/Q(B) ratios of 1.5, 2, and 5). Additional factors included in the model were filter flux (-12% lower f(KoA) for low- vs high-flux filters), ultra-filtration rate, and true Q(B) (lower than nominal Q(B) >= 200 ml/min). Of note, high Q(D)/Q(B) ratios used in children <= 6 years were associated with significant underprediction of K-D in vivo, with post-HD urea concentrations being 23% lower than expected. In conclusion, dialyzers should be characterized under pediatric conditions where high Q(D)/Q(B) ratios are used. Our model can be used to prevent underestimation of urea clearance, allowing shorter dialysis sessions, higher quality of life, and individualized treatment prescription in children on maintenance HD.