Augmented renal clearance

Augmented Renal Clearance (ARC) is a clinical condition characterized by an increased renal elimination of circulating solutes. It is commonly observed in critically ill patients, particularly those with trauma, burns, or sepsis. ARC can significantly affect the pharmacokinetics of drugs eliminated by the kidneys, potentially leading to subtherapeutic drug concentrations and treatment failure.

Definition

Augmented Renal Clearance is defined as a creatinine clearance (CrCl) greater than 130 mL/min/1.73m^2. This definition is based on the assumption that normal CrCl ranges from 90 to 130 mL/min/1.73m^2. However, the threshold for ARC may vary depending on the patient population and the method used to measure CrCl.

Pathophysiology

The exact mechanisms underlying ARC are not fully understood. However, several factors are thought to contribute to its development, including increased cardiac output, alterations in renal blood flow, and changes in tubular function. Inflammatory mediators released during critical illness may also play a role by increasing glomerular filtration and tubular secretion.

Clinical Implications

ARC can have significant implications for drug dosing in critically ill patients. Many drugs, including antibiotics, antivirals, and antifungals, are eliminated by the kidneys and their clearance can be significantly increased in patients with ARC. This can lead to subtherapeutic drug concentrations and potentially treatment failure. Therefore, it is important to identify patients with ARC and adjust drug dosing accordingly.

Measurement and Detection

Measurement of ARC typically involves the calculation of CrCl using either the Cockcroft-Gault equation or the Modification of Diet in Renal Disease (MDRD) study equation. However, these equations may not be accurate in critically ill patients due to changes in muscle mass and creatinine production. Direct measurement of CrCl using a timed urine collection is considered the gold standard, but it is time-consuming and not always feasible in clinical practice.

Management

Management of ARC primarily involves adjusting the dosing of renally eliminated drugs. In some cases, therapeutic drug monitoring may be necessary to ensure adequate drug concentrations. More research is needed to determine the optimal strategies for managing ARC in critically ill patients.

See Also

• Acute kidney injury
• Chronic kidney disease
• Pharmacokinetics
• Pharmacodynamics