Augmented Renal Clearance: What Have We Known and What Will We Do?

Luo, Yifan; Ma, Yue; Wang, Puxiu; Zhong, Jin; Chu, Yang

doi:10.3389/fphar.2021.723731

Cited by 17 publications

(15 citation statements)

References 89 publications

(114 reference statements)

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“…However, the understanding of the fundamental mechanisms of ARC is incomplete. Currently, three main mechanisms of ARC are widely accepted—namely, SIRS, renal function reserve (RFR), and brain–kidney crosstalk ( Cook and Hatton-Kolpek, 2019 ; Luo et al, 2021 ). Interestingly, all of them appear to be linked to the gut microbiota ( Figure 3 ).…”

Section: Gut–kidney Crosstalk In Sepsismentioning

confidence: 99%

Contribution of gut microbiota toward renal function in sepsis

Kong

Zhu

et al. 2022

Front. Microbiol.

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Sepsis most often involves the kidney and is one of the most common causes of acute kidney injury. The prevalence of septic acute kidney injury has increased significantly in recent years. The gut microbiota plays an important role in sepsis. It interacts with the kidney in a complex and multifactorial process, which is not fully understood. Sepsis may lead to gut microbiota alteration, orchestrate gut mucosal injury, and cause gut barrier failure, which further alters the host immunological and metabolic homeostasis. The pattern of gut microbiota alteration also varies with sepsis progression. Changes in intestinal microecology have double-edged effects on renal function, which also affects intestinal homeostasis. This review aimed to clarify the interaction between gut microbiota and renal function during the onset and progression of sepsis. The mechanism of gut–kidney crosstalk may provide potential insights for the development of novel therapeutic strategies for sepsis.

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Section: Gut–kidney Crosstalk In Sepsismentioning

confidence: 99%

Contribution of gut microbiota toward renal function in sepsis

Kong

Zhu

et al. 2022

Front. Microbiol.

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“…However, ARC in critical care settings is not uncommon [ 4 , 5 ]. This increased renal clearance above the normal range indicates a potential underdosing risk for many renally excreted drugs and contributes to treatment failure [ 6 – 8 ].…”

Section: Introductionmentioning

confidence: 99%

“…Previous ARC studies have reported its developmental mechanisms, prevalence, risk factors, and pharmacokinetics in renally excreted drugs [ 1 – 6 ]. Although there is a paucity of specific data on dosing regimens in patients with ARC, underdosing of antimicrobials is frequently reported and is an important issue in critically ill patients, where it is more likely to affect therapeutic outcomes [ 7 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

“…Despite the increased focus on ARC, a general lack of awareness about ARC and the need for continuous monitoring of urinary CrCl have impeded individualized drug design. Above all, the time course of ARC remains unknown, and the duration and risk factors for transient or persistent ARC symptoms are not clear [ 6 , 14 ]. In patients with ARC, higher doses than the standard is required for renally excreted drugs; however, the specific duration of administration is unknown.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2023

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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.

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“…Previous studies have identified young age, male sex, and illness severity as risk factors associated with the ARC phenomenon. Administration of vasopressor agents and saline loading may also increase the risk of ARC (Udy et al, 2010;Udy et al, 2013b;Luo et al, 2021). Previous studies have observed that patients with ARC have insufficient therapeutic concentrations of antibiotics; therefore, these patients are at a high risk of treatment failure.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of vancomycin pharmacokinetics in patients with augmented renal clearances: A randomized clinical trial

et al. 2022

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Purpose: Vancomycin is a narrow therapeutic window glycopeptide antibiotic that acts against Gram-positive bacteria. As it is renally eliminated, therapeutic drug monitoring is recommended for vancomycin, especially in case of kidney function alteration. Augmented renal clearance (ARC), defined as a creatinine clearance of more than 130 ml/min, is a risk factor for sub-therapeutic concentrations of vancomycin. This study aimed to evaluate the vancomycin pharmacokinetics following the administration of two different regimens in ARC patients.Methods: A randomized clinical trial (IRCT20180802040665N1) was conducted on patients in need of vancomycin therapy. Eight hours of urine was collected and 56 patients divided into two groups with creatinine clearance of more than 130 ml/min were included in the study. The first group received 15 mg/kg of vancomycin every 12 h and the second group 15 mg/kg every 8 h. After four doses, the peak and trough concentrations were measured from two blood samples. The primary outcome was the percentage of patients who attainted AUC more than 400. The occurrence of acute kidney injury also was evaluated after seven days.Results: The mean age of patients in the every 12 h and every 8 h groups was 44.04 ± 16.55 and 42.86 ± 11.83 years, respectively. While neurosurgical issues were the most common causes of hospitalization, central nervous infections were the most common indications for vancomycin initiation. Urinary creatinine clearance was 166.94 ± 41.32 ml/min in the every 12 h group and 171.78 ± 48.56 ml/min in the every 8 h group. 46.42% of patients in the every 12 h group and 82.14% of patients in the every 8 h group attained AUC/MIC of more than 400 mg × hr/L. None of the patients in the every 12 h group reached more than 15 mcg/ml concentration. At the 7-day follow-up, 10.7% patients in the BD group and 28.6% patients in the TDS group developed acute kidney injury (p = 0.089).Conclusion: Administration of vancomycin at a dose of 15 mg/kg every 8 h is associated with higher pharmacokinetic attainment in ARC patients. The occurrence of acute kidney injury also was not significantly higher in this therapeutic regimen. AUC/MIC monitoring is necessary in this population.

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Augmented Renal Clearance: What Have We Known and What Will We Do?

Cited by 17 publications

References 89 publications

Contribution of gut microbiota toward renal function in sepsis

Contribution of gut microbiota toward renal function in sepsis

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

Evaluation of vancomycin pharmacokinetics in patients with augmented renal clearances: A randomized clinical trial

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