Augmented Renal Clearance in Chinese Intensive Care Unit Patients After Traumatic Brain Injury: A Cross-Sectional Study
Augmented renal clearance (ARC) is a condition characterized by an enhanced elimination of circulating solutes, including drugs, by the kidneys at a rate significantly higher than normal. This phenomenon is particularly relevant in critically ill patients, as it can lead to suboptimal drug concentrations, treatment failure, and worse clinical outcomes. Despite its clinical importance, ARC remains understudied in certain patient populations, particularly in China, where traumatic brain injury (TBI) is a significant public health concern. This study aimed to investigate the incidence of ARC in Chinese TBI patients, evaluate the accuracy of commonly used formulas and scoring systems in identifying ARC, and determine the risk factors associated with this condition.
Background and Significance
ARC is defined as a 24-hour creatinine clearance (CrCl) of 130 mL/min or higher. It is frequently observed in critically ill patients, particularly those with TBI, and can persist for days to weeks after ICU admission. The condition has a substantial impact on the pharmacokinetics and pharmacodynamics of renally cleared drugs, necessitating individualized dosing strategies. However, the “one size fits all” approach to drug dosing in ARC patients is inappropriate, as it fails to account for the variability in renal function among these individuals.
The incidence of ARC in Australian TBI patients has been reported to be as high as 85%. In contrast, no studies have focused on ARC in Chinese TBI patients, leaving the incidence, risk factors, and diagnostic tools for this condition largely unknown. This study sought to address this gap by exploring the incidence of ARC in Chinese TBI patients, assessing the accuracy of four commonly used formulas and the Augmented Renal Clearance in Trauma Intensive Care (ARCTIC) scoring system in identifying ARC, and determining the risk factors associated with this condition.
Study Design and Methods
This prospective, single-center, cross-sectional study was conducted in a 24-bed ICU ward at a 2209-bed university hospital in Gansu Province, China, from October 1, 2018, to September 30, 2019. The study was approved by the ethics committee of the First Hospital of Lanzhou University, and informed consent was obtained from all participants. Patients were selected based on predefined criteria, and ARC was defined as a 24-hour CrCl of 130 mL/min or higher.
Patient characteristics and clinical features were extracted from medical records. Statistical analyses were performed using IBM-SPSS and MedCalc software, with differences considered statistically significant at a P-value of less than 0.05. The bias and precision of different formulas compared with the measured CrCl were evaluated using residual plots and the Bland and Altman method.
Results
A total of 54 patients were enrolled in the study, of whom 27 (50%) presented with ARC. The incidence of ARC was lower in patients with a medical history of hypertension (MHHT) (3/16) compared to the overall incidence of 50% (27/54). The dose of mannitol used for hyperosmolar therapy did not differ significantly between the ARC and non-ARC groups. However, the ARC group had a lower serum creatinine (Scr) concentration (56 mg/dL) compared to the non-ARC group (65 mg/dL). The mean 24-hour CrCl of patients with ARC was significantly higher (175.13 mL/min) than that of patients without ARC (101.35 mL/min).
The estimated glomerular filtration rate (eGFR) of patients with ARC was significantly higher than that of patients without ARC, except for the eGFR calculated by the Chronic Kidney Disease Epidemiology Collaboration equation for Asian people (CKD-EPI-Asian). Correlation analysis revealed a moderate correlation between measured 24-hour CrCl and four calculated eGFRs. In the ARC subgroup, each formula underestimated CrCl, with a more significant bias and lower precision observed in the ARC group.
The ARCTIC scoring system, a predictive model used to screen for ARC among trauma patients, showed a weak positive correlation (0.269) between CrCl and ARCTIC scores. The scoring system had a sensitivity of 88.9% but a specificity of only 29.6%. Receiver operating characteristic (ROC) analysis demonstrated that the Cockcroft-Gault (CG) formula had the highest positive predictive value (PPV) (68.59%), while the Japanese eGFR (J-eGFR) had the highest negative predictive value (NPV) (92.31%). Only the CG formula presented an area under the curve (AUC) greater than 0.75 for detecting ARC, with a cutoff value of 95.69 mL/min.
Risk Factors for ARC
Several variables were significantly different between patients with and without ARC, including Scr (56.0 vs. 65.0 mg/dL) and the rate of MHHT (5.6% vs. 24.1%). Although age and body mass index (BMI) did not differ significantly between the two groups, the difference approached significance. Multiple logistic regression analysis identified male sex, higher BMI, lower Scr, and the absence of MHHT as independent risk factors for ARC. The model constructed using these variables had sensitivity, specificity, PPV, and NPV all above 70%.
Further logistic regression models incorporating the cutoff values of four eGFRs and other risk factors, such as BMI and MHHT, demonstrated a good fit and improved accuracy in predicting ARC compared to eGFR alone. These models had good sensitivity, specificity, PPV, and NPV, with specificity improving dramatically compared to eGFR.
Discussion
This study is the first to investigate ARC in Chinese TBI adult patients. The incidence of ARC among the study population was 50%, which is lower than the 85% reported in Australian TBI patients. The difference in incidence may be attributed to variations in ethnicity and brain injury severity among the patient populations. The study also found that none of the four eGFR formulas or the ARCTIC scoring system accurately predicted the occurrence of ARC. However, multivariable analysis showed that an eGFR above the optimal cutoff values combined with the absence of MHHT and/or a higher BMI could be used as a useful tool to identify ARC in Chinese TBI patients.
The ARCTIC scoring system, which was developed to facilitate the identification of ARC in trauma patients, was not accurate when applied to Chinese TBI patients. This discrepancy may be due to differences in patient populations and injury mechanisms between the studies. The study also found that male sex, higher BMI, lower Scr, and the absence of MHHT were independent predictors of ARC. While younger age has been previously associated with ARC, this study did not find a significant difference in age between the ARC and non-ARC groups, possibly due to the older age of the study population.
Conclusion
ARC is frequently observed in Chinese TBI patients, with an incidence of 50% in this study. Neither eGFR nor the ARCTIC score could be directly used as a screening tool to identify high CrCl. However, combining the cutoff value of eGFR with other characteristics, such as the absence of MHHT and/or a higher BMI, could be a useful tool for screening ARC in TBI patients. These findings highlight the need for individualized dosing strategies in ARC patients to ensure optimal drug concentrations and treatment outcomes.
doi.org/10.1097/CM9.0000000000001572
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