Urea dialyzer clearance (KD) has been suggested to be underpredicted from blood flow (QB), dialysate flow (QD), 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 (fKoA) required for unbiased KD and post-HD urea concentration predictions in vivo. QD/QB ratio was most strongly associated with individual fKoA estimates (P < 0.001; fKoA = −1%, 18%, and 110% at QD/QB ratios of 1.5, 2, and 5). Additional factors included in the model were filter flux (−12% lower fKoA for low- vs high-flux filters), ultra-filtration rate, and true QB (lower than nominal QB ≥200 ml/min). Of note, high QD/QB ratios used in children ≤6 years were associated with significant underprediction of KDin vivo, with post-HD urea concentrations being 23% lower than expected. In conclusion, dialyzers should be characterized under pediatric conditions where high QD/QB 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.
From the *Pediatric Pharmacology & Pharmacometrics, University of Basel Children’s Hospital, Basel, Switzerland
†Pediatric Nephrology, Yale University School of Medicine, New Haven, Connecticut.
Submitted for consideration July 2018; accepted for publication in revised form December 2018.
Disclosures: Marc Pfister is a consultant at Certara Company. Drs Verena Gotta and Olivera Marsenic declare that they have no relevant financial interests.
This project has been supported by the Research Fund for Junior Researchers, University of Basel, Switzerland and by the Eckenstein-Geigy Foundation, which is sponsoring research at Pediatric Pharmacology at University Children’s Hospital Basel.
Supplemental digital content is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML and PDF versions of this article on the journal’s Web site (www.asaiojournal.com)
Correspondence: Verena Gotta, Pediatric Pharmacology & Pharmacometrics, University of Basel Children’s Hospital Spitalstrasse 33 4031 Basel, Switzerland. Email: email@example.com.