Augmented renal clearance: a retrospective, cohort study of urinary creatinine clearance in critically ill patients in the United Kingdom.

Brian W Johnston,Martyn Habgood,Anton Krige,Miland Joshi,David Perry

doi:10.1177/03000605211015573

Abstract

ObjectiveAugmented renal clearance (ARC) is associated with sub-therapeutic antibiotic, anti-epileptic, and anticoagulant serum concentrations leading to adverse patient outcomes. We aimed to describe the prevalence and associated risk factors for ARC development in a large, single-centre cohort in the United Kingdom.MethodsWe conducted a retrospective observational study of critically unwell patients admitted to intensive care between 2014 and 2016. Urinary creatinine clearance was used to determine the ARC prevalence during the first 7 days of admission. Repeated measures logistic regression was used to determine risk factors for ARC development.ResultsThe ARC prevalence was 47.0% (95% confidence interval [95%CI]: 44.3%–49.7%). Age, sex, Acute Physiology and Chronic Health Evaluation (APACHE) II score, and sepsis diagnosis were significantly associated with ARC. ARC was more prevalent in younger vs. older (odds ratio [OR] 0.95 [95%CI: 0.94–0.96]), male vs. female (OR 0.32 [95%CI: 0.26–0.40]) patients with lower vs. higher APACHE II scores (OR 0.94 [95%CI: 0.92–0.96]).ConclusionsThis patient group probably remains unknown to many clinicians because measuring urinary creatinine clearance is not usually indicated in this group. Clinicians should be aware of the ARC risk in this group and consider measurement of urinary creatinine clearance.

Highlights

During critical illness a number of pathophysiological factors alter the pharmacokinetic and pharmacodynamic (PK/PD) handling of drugs.[1]
We aimed to examine the prevalence of augmented renal clearance (ARC), determine risk factors associated with ARC, investigate the development of ARC during the first 7 days of critical illness, and assess whether the Augmented Renal Clearance in Trauma Intensive Care (ARCTIC) score can be used as a screening tool for ARC in a cohort of mixed surgical and medical patients admitted to an intensive care unit (ICU) in the United Kingdom
Following exclusion of patients who were admitted with or developed acute kidney injury (AKI) during their ICU stay, required renal replacement therapy (RRT), or had documented Kidney Disease: Improving Global Outcomes (KDIGO) stage 5 chronic kidney disease (CKD) or end-stage renal failure (ESRF), data for 1328 individual patients were available for analysis (Figure 1)

Summary

Introduction

During critical illness a number of pathophysiological factors alter the pharmacokinetic and pharmacodynamic (PK/PD) handling of drugs.[1] Alterations in hepatic enzyme activity, plasma protein concentration, and the volume of distribution (Vd) of drugs are common.[1] organ failure and in particular renal failure can result in reduced elimination of drugs, potentially leading to accumulation and toxicity.[2,3]. Routine monitoring of renal function has traditionally been aimed at detecting renal impairment and drugs relying on renal elimination should undergo dose adjustment to prevent toxicity.[2,3,4]. The phenomenon of a state of supra-physiological renal function known as augmented renal clearance (ARC) is increasingly recognised.[2,4] ARC is defined as enhanced renal clearance and elimination of circulating solutes and is thought to be driven by a physiological increase in glomerular filtration rate (GFR).[5]

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