Scoping review of augmented renal clearance in critically ill pediatric patients

Augmented renal clearance (ARC), a phenomenon of enhanced elimination of renal solutes, has been described in adult critically ill patients, but little is known about the phenomenon in children. The aim of this scoping review was to gather and summarize all evidence on ARC in pediatric patients to examine its breadth and depth including prevalence, risk factors, and pharmacokinetic alterations and identify any gaps for further areas of inquiry. PubMed, Embase, and Web of Science were searched for titles, abstracts, or keywords that focused on ARC. Non-English studies, reviews, and nonhuman studies were excluded. Reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews (PRISMA-ScR) guidelines. Data were extracted on article type, study details, patient population, ARC definition and prevalence, methods of renal function assessment, and study results. A total of 215 citations were found with 25 citations meeting the criteria for inclusion in pediatrics (2102 total patients); the majority of studies (84%) focused on pharmacokinetics (PK) of antimicrobial agents. The median/mean age range was 1.25-12 years. There were a total of 10 different definitions of ARC. The prevalence of ARC ranged from 7.8% to 78%. The most common method for documenting creatinine clearance (CrCl) was the modified Schwartz equation (64%). Only 20% of studies reported risk factors for ARC including low serum creatinine, increasing age, febrile neutropenia, male, septic shock, and treatment with antibiotics. Glycopeptide antimicrobials were the most evaluated class (42.9%) among the 21 antimicrobial drug studies. All studies reported increased drug clearance and/or poor probability of achieving target concentrations of the agents studied. ARC showed variable prevalence in pediatric patients likely due to the lack of a standard definition and many studies not considering age-related changes in CrCl with pediatric intensive care unit (PICU) patients. ARC was shown to impact PK of antibiotics commonly administered to pediatric patients, which may necessitate changes in standard dosing regimens.