Onset timing and duration of augmented renal clearance in a mixed intensive care unit

Abstract

Background Augmented renal clearance (ARC) is associated with lower blood plasma concentrations of renally excreted drugs; however, its time course is unknown. The current study aimed to determine the onset timing/duration of ARC, its risk factors, and its association with clinical outcomes by continuous monitoring of urinary creatinine clearance (CrCl) in critically ill patients. Methods Data were retrospectively obtained from the medical records of 2592 critically ill patients admitted to the intensive care unit (ICU) from January 2019 to June 2022 at a tertiary emergency hospital. Among these, patients with continuously measured urinary CrCl were selected and observed over time. We evaluated the onset timing and duration of ARC by plotting Kaplan–Meier curves. Furthermore, by multivariate analyses, factors associated with the onset and persistence of ARC were analyzed, and the association between the ARC time course and clinical outcomes was evaluated. Results The prevalence of ARC was 33.4% (245/734). ARC onset was within 3 days of admission in approximately half of the cases, and within 1 week in most of the other cases. In contrast, the persistence duration of ARC varied widely (median, 5 days), and lasted for more than a month in some cases. Multivariate analysis identified younger age, male sex, lower serum creatinine at admission, admission with central nervous system disease, no medical history, use of mechanically assisted ventilation, and vasopressor use as onset factors for ARC. Furthermore, factors associated with ARC persistence such as younger age and higher urinary CrCl on ARC day 1 were detected. The onset of ARC was significantly associated with reduced mortality, but persistent of ARC was significantly associated with fewer ICU-free days. Conclusions Despite the early onset of ARC, its duration varied widely and ARC persisted longer in younger patients with higher urinary CrCl. Since the duration of ARC was associated with fewer ICU-free days, it may be necessary to consider a long-term increased-dose regimen of renally excreted drugs beginning early in patients who are predicted to have a persistent ARC.

Model-Informed Precision Dosing of Imipenem in an Obese Adolescent Patient with Augmented Renal Clearance and History of Schizophrenia

“…A study found that the overall prevalence of ARC in patients older than 18 years was as high as 24.6%. 12,28 The risk factors for the occurrence of ARC are also including trauma, young age, and male sex which were exist in this patient. 11 Another multivariate analysis identified younger age, male sex, lower serum creatinine at admission, admission with central nervous system disease, no medical history, use of mechanical ventilation, and use of vasopressor as onset factors for ARC.…”

“…11 Another multivariate analysis identified younger age, male sex, lower serum creatinine at admission, admission with central nervous system disease, no medical history, use of mechanical ventilation, and use of vasopressor as onset factors for ARC. 12 This patient had several risk factors including younger age, male sex, vasopressor use and use of mechanically assisted ventilation. For ARC patients exposed to β-lactam antibiotics, the drug concentration is easily lower than the therapeutic target.…”

“…10 ARC is common in intensive care unit (ICU) patients, while trauma, young age, male sex, admission with central nervous system disease, use of mechanical ventilation, and use of vasopressor were independent risk factors for ARC. 11,12 These patients may have insufficient drugs exposure due to excessive elimination. Adolescent critically ill patients with ARC and history of schizophrenia were not clinically typical, and there were few case reports of imipenem dose adjustment in these patients.…”

Pharmacokinetics of Antibacterial Agents in the Elderly: The Body of Evidence

“…In critically ill patients with cancer ARC development on the first day of intensive care unit (ICU) admission demonstrated a significant association with younger age (OR 1.028, 95% CI: 1.005–1.051) [ 264 ]. Despite the association with young age stated above a retrospective study of 2592 critically ill patients admitted to the ICU revealed that the median age of patients with ARC was 70 (55–79) years, with a prevalence of 33.4% [ 265 ], pointing out the importance of the ARC for the elderly population. This state can lead to decreased AB exposure and thus to treatment failure with beta-lactams, aminoglycosides, glycopeptides, and other, mainly hydrophilic agents [ 262 ].…”

LC-MS/MS-Based Serum Metabolomics and Transcriptome Analyses for the Mechanism of Augmented Renal Clearance

“…Augmented Renal Clearance (ARC), most commonly defined as a glomerular filtration rate (GFR) of >130 mL/min/1.73 m 2 [ 1 ], is a phenomenon of increased renal clearance of circulating solutes that has received increasing attention due to its negative effects of inadequate drug exposure, poor efficacy, and the increased risk of resistant bacteria [ 2 , 3 ]. ARC often occurs in critically ill people with ailments such as burns, sepsis, cancer, multiple injuries, and subarachnoid hemorrhaging [ 4 , 5 , 6 , 7 ]. ARC has also been reported in patients with coronavirus disease 2019 (COVID-19) [ 8 , 9 , 10 ].…”