Augmented Renal Clearance
Augmented renal clearance (ARC) has been recently described in some subsets of critically ill patients. This condition is often overlooked by clinicians, although it can have profound and severe consequences on the efficacy of drugs that are predominantly
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Augmented Renal Clearance João Pedro Baptista
7.1 Introduction Renal clearance is the process by which the kidneys eliminate circulating metabolites, toxins, waste products, and drugs. This involves filtration, secretion, and reabsorption. Along with the liver, the kidneys constitute a key organ in human body homeostasis. From a physiological point of view, renal clearance is the volume of plasma from which a substance is completely removed by the kidney in a given amount of time. This process affects predominantly hydrophilic substances, as is the case for most antibiotics. These drugs are crucial to the successful treatment of sepsis and septic shock in the intensive care unit (ICU). However, critically ill patients are different from those encountered in a ward setting. Critical illness and its therapies often induce profound pathophysiological changes, contributing to inadequate antibiotic therapy. Hypoalbuminaemia, expansion of the volume of distribution (Vd), tissue hypoperfusion, organ dysfunction, use of vasoactive drugs, and the co-existence of renal replacement or extracorporeal membrane oxygenation therapies are among the most important factors. Renal dysfunction is common in critical care settings, and is often a focus for clinicians. Indeed, the converse—supra-normal function of the kidneys is infrequently considered.
J.P. Baptista Intensive Care Unit, Centro Hospitalar e Universitário de Coimbra (CHUC), Coimbra, Portugal e-mail: [email protected] © Springer Nature Singapore Pte Ltd. 2018 A.A. Udy et al. (eds.), Antibiotic Pharmacokinetic/Pharmacodynamic Considerations in the Critically Ill, DOI 10.1007/978-981-10-5336-8_7
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This chapter will focus on the key aspects of the concept, diagnosis, pathophysiology, epidemiology, and clinical implications of augmented renal clearance (ARC) in the critically ill patient.
7.2 Definition of Augmented Renal Clearance According to Udy et al. [1], ARC is defined as the enhanced renal elimination of circulating solutes as compared with an expected baseline. However, to date, there is no standard accepted definition of an accurate cut-off value to define ARC and there are several reasons for this. First, although the clinical recognition of ARC is by all means not recent [2], it was only in the last few years that a considerable amount of medical literature emerged reporting the features of ARC in the critically ill. Second, the “normal” values of glomerular filtration rate (GFR) physiologically decline with age, depend on sex, race, and body surface area, and show important variation within normal individuals. Third, different groups of investigators have used varying cut-offs to define ARC, between 120 and 160 mL/ min/1.73 m2. Finally, several methods have been used to measure or estimate the GFR, leading to significant heterogeneity in the results, and difficulties in interpretation and comparison. The concept of ARC is likely more dynamic, representing the changeable physiology encountered when the body reacts to an acu
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