Augmented Renal Clearance: An Under-Recognized Phenomenon Associated With COVID-19

Rhoney, Denise H.; Brooks, Ashley; Nelson, Nicholas R.

doi:10.1097/cce.0000000000000617

Cited by 5 publications

(5 citation statements)

References 36 publications

(139 reference statements)

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“…These patients have a different clinical presentation and course during their ICU stay compared with other critically ill patients [ 21 ]. Nevertheless, COVID-19 patients might experience systemic inflammatory response syndrome, which can (in-)directly overlap with the mechanism of ARC [ 16 ] and consequently increase ARC risk. In addition, a specific pathophysiological mechanism might play a role here, as viral particles have been found in the kidneys of COVID-19 patients.…”

Section: Discussionmentioning

confidence: 99%

“…Patients with COVID-19 mainly present with respiratory failure, but many critically ill COVID-19 patients also suffer from kidney dysfunction, with an acute kidney injury (AKI) prevalence of 18–81% [ 15 ]. On the other side of the renal function spectrum, ARC is common in critically ill COVID-19 patients, with a prevalence of 25–72% [ 16 ]. While the epidemiology of ARC has been described in critically ill COVID-19 patients [ 16 , 17 , 18 , 19 , 20 ], the performance of prediction models for ARC has not been reported in this patient population.…”

Section: Introductionmentioning

confidence: 99%

“…On the other side of the renal function spectrum, ARC is common in critically ill COVID-19 patients, with a prevalence of 25–72% [ 16 ]. While the epidemiology of ARC has been described in critically ill COVID-19 patients [ 16 , 17 , 18 , 19 , 20 ], the performance of prediction models for ARC has not been reported in this patient population. Therefore, we aim to externally validate the ARC predictor in previously unseen critically ill COVID-19 patients.…”

Section: Introductionmentioning

confidence: 99%

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External Validation of the Augmented Renal Clearance Predictor in Critically Ill COVID-19 Patients

et al. 2023

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The ARC predictor is a prediction model for augmented renal clearance (ARC) on the next intensive care unit (ICU) day that showed good performance in a general ICU setting. In this study, we performed a retrospective external validation of the ARC predictor in critically ill coronavirus disease 19 (COVID-19) patients admitted to the ICU of the University Hospitals Leuven from February 2020 to January 2021. All patient-days that had serum creatinine levels available and measured creatinine clearance on the next ICU day were enrolled. The performance of the ARC predictor was evaluated using discrimination, calibration, and decision curves. A total of 120 patients (1064 patient-days) were included, and ARC was found in 57 (47.5%) patients, corresponding to 246 (23.1%) patient-days. The ARC predictor demonstrated good discrimination and calibration (AUROC of 0.86, calibration slope of 1.18, and calibration-in-the-large of 0.14) and a wide clinical-usefulness range. At the default classification threshold of 20% in the original study, the sensitivity and specificity were 72% and 81%, respectively. The ARC predictor is able to accurately predict ARC in critically ill COVID-19 patients. These results support the potential of the ARC predictor to optimize renally cleared drug dosages in this specific ICU population. Investigation of dosing regimen improvement was not included in this study and remains a challenge for future studies.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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External Validation of the Augmented Renal Clearance Predictor in Critically Ill COVID-19 Patients

et al. 2023

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“…Rhoney et al [7] have summarized the current literature on ARC and COVID‐19 and describe noticeable differences between ARC in the general ICU population and COVID‐19 in onset and duration. Patients with COVID‐19 appear to have a delayed onset of ARC (13–28 days after admission) compared to those without (1–3 days after admission).…”

Section: Discussionmentioning

confidence: 99%

“…The underlying physiology is not yet resolved but may be mediated by a systemic inflammatory response, utilizing renal function reserves and leading to a hyperdynamic circulation with increased renal perfusion [6]. In critically ill patients with COVID-19, it may have a similar pathophysiology [7]. ARC can lead to faster elimination of hydrophilic drugs, leading to subtherapeutic concentrations and possibly treatment failure [1][2][3][4]8].…”

Section: Introductionmentioning

confidence: 99%

Treatment implications of augmented renal clearance in a critically ill COVID‐19 patient: A case report

Deenen

Fransen

Jaspers

et al. 2023

Fundamemntal Clinical Pharma

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Augmented renal clearance (ARC) is a pathophysiological phenomenon that can occur in critically ill patients, leading to enhanced renal function. It is defined as a creatinine clearance of >130 mL/min/1.73 m2. ARC can lead to subtherapeutic levels of renally cleared drugs and subsequent treatment failure. In COVID‐19, it has only been described in the literature in a few cases. We present the case of a 38‐year‐old critically ill patient with COVID‐19 who developed ARC with an initial clearance of 226 mL/min/1.73 m2, persisting for 30 days. He required high doses of sedatives and neuromuscular blocking agents, as well as increased doses of vancomycin and dalteparin, to reach adequate serum levels. This case emphasizes the importance for clinicians to consider ARC in the dosing of all renally cleared drugs, including antibiotics, low molecular weight heparins, and sedatives, to prevent subtherapeutic drug levels and treatment failure.

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What is New in Augmented Renal Clearance in Septic Patients?

Baptista,

Moura,

Silva

et al. 2023

Curr Infect Dis Rep

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Purpose of Review In this narrative review encompassing relevant scientific publications regarding critically ill patients in the last 5 years, we discuss key questions regarding the concept, pathophysiology, identification, epidemiology, and implications of augmented renal clearance (ARC) in the treatment of sepsis. Recent Findings Mathematical estimates of renal function show low accuracy when evaluating renal function in the intensive care unit, jeopardizing the correct dosing of antimicrobials. The description of ARC in critically ill patients in several, distant geographical areas worldwide reveals that this condition is more frequent than anticipated. Several new risk factors have been recently reported, needing future confirmation. Pathophysiology is still largely unknown; however, intact kidney physiology, inflammatory mediators, and tubular secretion seem to play a role. Several studies have demonstrated the association between ARC and subtherapeutic levels of several β-lactams, vancomycin, and fluconazole. Lately, there have been recommendations of dosage regimen adjustments for patients with ARC, namely, through increases in total daily dose or prolonged infusion for various antimicrobials. Literature is scarce describing the influence of ARC on clinical outcomes of patients receiving antibiotics, and results are contradictory. Summary Growing body of evidence supports that measured creatinine clearance based on time-defined urine output is strongly recommended for the identification of ARC and for reliable evaluation of its prevalence and risk factors. Clinicians should be alert for the need to use off-label dosing of antimicrobials in septic patients showing ARC. Concise recommendations for antibiotic dosage regimens, based on clinical data, are still needed.

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Augmented Renal Clearance: An Under-Recognized Phenomenon Associated With COVID-19

Cited by 5 publications

References 36 publications

External Validation of the Augmented Renal Clearance Predictor in Critically Ill COVID-19 Patients

External Validation of the Augmented Renal Clearance Predictor in Critically Ill COVID-19 Patients

Treatment implications of augmented renal clearance in a critically ill COVID‐19 patient: A case report

What is New in Augmented Renal Clearance in Septic Patients?

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