Augmented Renal Clearance in Critically Ill Patients: A Systematic Review

Traditionally, renal function in critically ill patients has been assessed to identify renal dysfunction, and dose adjustment is generally accepted in such a context. Nevertheless, augmented renal clearance (ARC) is a less well-studied phenomenon that could lead to faster elimination of drugs, resulting in subtherapeutic concentrations and poorer clinical outcomes when standard dosage guidelines are followed. The aim of this systematic review was to gather and summarise all the available evidence on ARC in critically ill patients, including its definition, underlying mechanisms, epidemiology, diagnosis and impact on both drug pharmacokinetics and clinical outcomes. A systematic review was conducted to include all the original studies that provided information on ARC in critically ill patients, and is reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Augmented renal clearance, defined as a creatinine clearance (CrCl) > 130 mL/min/1.73 m(2), preferably measured in urine, is present in 20-65% of critically ill patients. Younger age, polytrauma and lower severity illness have been identified as risk factors. An influence of ARC on antimicrobial pharmacokinetics has been observed, with ARC consistently being associated with subtherapeutic antibiotic plasma concentrations. ARC is a prevalent condition in critically ill patients, especially in young people, with urinary CrCl being the best diagnostic method because mathematical estimates tend to underestimate CrCl. ARC increases renal drug elimination and has a clear influence on certain antimicrobial plasma levels, but is yet to define its impact on clinical outcomes and on pharmacokinetics of other types of drugs. Research on the need to stage ARC and establish specific dosing guidelines is warranted.