Augmented Renal Clearance in Critical Illness: An Important Consideration in Drug Dosing

Abstract

Augmented renal clearance (ARC) is a manifestation of enhanced renal function seen in critically ill patients. The use of regular unadjusted doses of renally eliminated drugs in patients with ARC might lead to therapy failure. The purpose of this scoping review was to provide and up-to-date summary of the available evidence pertaining to the phenomenon of ARC. A literature search of databases of available evidence in humans, with no language restriction, was conducted. Databases searched were MEDLINE (1946 to April 2017), EMBASE (1974 to April 2017) and the Cochrane Library (1999 to April 2017). A total of 57 records were included in the present review: 39 observational studies (25 prospective, 14 retrospective), 6 case reports/series and 12 conference abstracts. ARC has been reported to range from 14 to 80%. ARC is currently defined as an increased creatinine clearance of greater than 130 mL/min/1.73 m2 best measured by 8–24 h urine collection. Patients exhibiting ARC tend to be younger (<50 years old), of male gender, had a recent history of trauma, and had lower critical illness severity scores. Numerous studies have reported antimicrobials treatment failures when using standard dosing regimens in patients with ARC. In conclusion, ARC is an important phenomenon that might have significant impact on outcome in critically ill patients. Identifying patients at risk, using higher doses of renally eliminated drugs or use of non-renally eliminated alternatives might need to be considered in ICU patients with ARC. More research is needed to solidify dosing recommendations of various drugs in patients with ARC.

Therapeutic Drug Monitoring of Levetiracetam in Select Populations

“…Critically ill patients are those who require admission to the intensive care unit due to lifethreatening medical conditions such as respiratory failure, septic shock and severe traumatic brain injury. In those patients, the phenomenon of augmented renal clearance (ARC) has been well described (65) and may present a challenge for the use of LEV in these patients as it is cleared primarily by the renal route. ARC, otherwise known as glomerular hyperfiltration or enhanced renal clearance, indicates an increase in kidney function that results in an augmentation of drug clearance and the possibility of treatment failure.…”

Therapeutic Drug Monitoring of Meropenem and Piperacillin in Critical Illness—Experience and Recommendations from One Year in Routine Clinical Practice

“…As both meropenem and piperacillin are mainly eliminated renally, renal function is one of the most influential factors of the concentrations in the bloodstream. Accordingly, young patients with hyperdynamic kidney function are at a higher risk for subtherapeutic concentrations [20][21][22][23]. In contrast, acute kidney failure leads to a significant increase in the half-life of the drugs, with a risk of accumulation and toxic adverse effects [24].…”

Pharmacokinetics/Pharmacodynamics of β-Lactams and Therapeutic Drug Monitoring: From Theory to Practical Issues in the Intensive Care Unit

“…5 Conversely, enhanced renal function may occur during septic shock, termed "augmented renal clearance" (ARC), leading to subtherapeutic concentrations and the risk of therapeutic failure. 22,23 Extracorporeal circuits such as RRT or plasma exchange may also affect the Cl of hydrophilic antibiotics. 5 There is no clear consensus regarding the most appropriate method of estimating renal function in critically ill patients.…”

“…ARC is most commonly defined as a CrCl > 130 mL/minute/ 1.73 m 2 , and this phenomenon can lead to an increase in Cl of β-lactams antibiotics, suboptimal drug concentrations, and treatment failure. 22,23 To date, the presence of ARC has not been associated with worse patient outcomes. The prevalence of ARC in a cohort of 254 septic shock patients was observed to be 65.1% (n ¼ 183).…”