Augmented Renal Clearance

Abstract

Augmented renal clearance (ARC) is a phenomenon in critically ill patients characterized by increased creatinine clearance and elimination of renally eliminated medications. Patients with severe neurologic injury, sepsis, trauma, and burns have been consistently identified as at risk of ARC, with mean creatinine clearances ranging from 170 ml/minute to more than 300 ml/minute. Several potential mechanisms may contribute to the occurrence of ARC including endogenous responses to increased metabolism and solute production, alterations in neurohormonal balance, and therapeutic maneuvers such as fluid resuscitation. Augmented renal clearance is associated with suboptimal exposure to critical medications, including β‐lactams and vancomycin, increasing the risk of treatment failure. Although definitive screening tools are not yet known, critical care pharmacists must be vigilant in recognizing when ARC may be a contributing factor affecting expected treatment outcomes in individual patients. Optimizing dosing strategies in critically ill patients with ARC remains a goal of continued research. The current review discusses the clinical characteristics and methods of identifying patients at risk of ARC, potential mechanisms for ARC, and describes pharmacotherapy dosing considerations in patients with ARC.

Determination of optimal loading and maintenance doses for continuous infusion of vancomycin in critically ill patients: Population pharmacokinetic modelling and simulations for improved dosing schemes

“…The current simulation suggested that daily doses of 350 0-450 0 mg should be considered for such patients, which is in line with a nomogram previously proposed for critically-ill patients [30] . This may require early identification and separation of ARC patients from the general population, but is feasible as these patients are typically young and with trauma, burn injuries, or acute leukaemia [31,32] . A serum creatinine < 0.4 mg/dL could also serve as a surrogate marker for ARC during the treatment [17] .…”

“…Vancomycin is not significantly metabolised in humans. Its elimination primarily depends on renal function [29,32] (with non-renal clearance being probably < 5% of the total drug clearance), which the current model and proposed dosing strategies fully consider, and its plasma levels are not influenced by the activity of renal transport systems [33] . Moreover, all current data were adjusted to a standard creatinine clearance of 100 mL/min for a nominal 70-kg subject, allowing easy comparison and translation to patients with different renal function and weight.…”

Development and external validation of an online clinical prediction model for augmented renal clearance in adult mixed critically ill patients: the ARC predictor

“…Augmented renal clearance (ARC), referring to enhanced renal elimination, has been identified during the last decade to be of significant clinical importance in patients admitted at the intensive care unit (ICU). Reported incidences for ARC in the ICU vary between 16-100% depending on the subset of patients and the definition employed for ARC [1][2][3][4]. ARC has the potential to result in subtherapeutic plasma levels and consequent therapeutic failure as the kidney is the primary excretory pathway for many (hydrophilic) drugs [5][6][7][8][9][10][11][12].…”

Variables Impacting GFR Estimation Method for Drug Dosing in Ckd: Artificial Neural Network Prediction Model

“…Dosing of medications in CKD patients is further complicated by the very nature of the dose-response interaction for the various medications. Some medications need high peak levels, whereas others require less fluctuation of the levels over the dosing intervals [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18]. For example, aminoglycoside antibiotics are an example of the former, whereas β-lactams are a representative of the latter [19][20][21][22].…”