Select Critically ill Patients at Risk of Augmented Renal Clearance: Experience in a Malaysian Intensive Care Unit

Abstract

Augmented renal clearance (ARC) refers to increased solute elimination by the kidneys. ARC has considerable implications for altered drug concentrations. The aims of this study were to describe the prevalence of ARC in a select cohort of patients admitted to a Malaysian intensive care unit (ICU) and to compare measured and calculated creatinine clearances in this group. Patients with an expected ICU stay of >24 hours plus an admission serum creatinine concentration <120 μmol/l, were enrolled from May to July 2013. Twenty-four hour urinary collections and serum creatinine concentrations were used to measure creatinine clearance. A total of 49 patients were included, with a median age of 34 years. Most study participants were male and admitted after trauma. Thirty-nine percent were found to have ARC. These patients were more commonly admitted in emergency ( P=0.03), although no other covariants were identified as predicting ARC, likely due to the inclusion criteria and the study being under-powered. Significant imprecision was demonstrated when comparing calculated Cockcroft-Gault creatinine clearance (Crcl) and measured Crcl. Bias was larger in ARC patients, with Cockcroft-Gault Crcl being significantly lower than measured Crcl ( P <0.01) and demonstrating poor correlation (rs=-0.04). In conclusion, critically ill patients with ‘normal’ serum creatinine concentrations have varied Crcl. Many are at risk of ARC, which may necessitate individualised drug dosing. Furthermore, significant bias and imprecision between calculated and measured Crcl exists, suggesting clinicians should carefully consider which method they employ in assessing renal function.

Augmented renal clearance in critically ill patients: etiology, definition and implications for beta-lactam dose optimization

“…Estimates of CL CR (e.g. using the Cockcroft-Gault equation) may also significantly differ from the actual measured value [7,19,20]. Although mathematical equations consider some demographic patient factors, they do not account for the unique pathophysiologic factors and the use of cardio-active medications in the critically ill that affect renal function.…”

Implications of Augmented Renal Clearance on Drug Dosing in Critically Ill Patients: A Focus on Antibiotics

“…The CG and the Modification of Diet in Renal Disease (MDRD) equations have been validated only in the settings of stable renal function and chronic renal impairment, respectively; therefore, they have limited utility in the setting of unstable (i.e., fluctuating) renal function . In addition, these equations have a low sensitivity in patients with reduced protein stores and malnourishment . Serum creatinine concentration can also be affected by age, sex, race, metabolic state, diet, and degree of hydration, which can yield inaccurate results when using these two methods .…”

“…25 In addition, these equations have a low sensitivity in patients with reduced protein stores and malnourishment. 3,26 Serum creatinine concentration can also be affected by age, sex, race, metabolic state, diet, and degree of hydration, which can yield inaccurate results when using these two methods. 26 Although CrCl estimations based on the CG equation may accurately predict renal function in clinically stable patients, there is poor correlation between estimated CrCl and measured CrCl using a 24-hour urine collection in critically ill patients.…”

“…ARC is hypothesized to occur due to increased glomerular filtration, although the role of enhanced tubular secretion and reabsorption is unclear. Regardless, ARC leads to increased solute (e.g., medication) elimination by the kidneys; therefore, as in patients with renal dysfunction, potential medication dosage adjustments should be considered in critically ill patients with ARC …”

“…Regardless, ARC leads to increased solute (e.g., medication) elimination by the kidneys; therefore, as in patients with renal dysfunction, potential medication dosage adjustments should be considered in critically ill patients with ARC. [2][3][4] The objective of this review is to characterize ARC in the critically ill by describing the incidence of ARC and its associated risk factors, reviewing screening methods and assessment strategies, and illustrating its effect on in vivo drug concentrations and clinical outcomes. In addition, this review will examine strategies to overcome ARC and summarize current pharmacokinetic and pharmacodynamic studies in patients with ARC in an effort to provide dosing guidance for this patient population.…”