The “Dilution Effect” of Augmented Renal Clearance on the Prognostic Utility of NT-proBNP in Patients with Severe Traumatic Brain Injury

Jiaxin Dong, Qian Zhang, Min Huang, Jing Zhou, Suming Zhou, Dongmei Zhu Department of Geriatrics ICU, Critical Care Center, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 210029, People’s Republic of ChinaCorrespondence: Dongmei Zhu, Department of Geriatrics ICU, Critical Care Center, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 210029, People’s Republic of China, Email [email protected]: Augmented renal clearance (ARC) constitutes a prevalent phenomenon in patients with severe traumatic brain injury (sTBI). Although N-terminal pro-B-type natriuretic peptide (NT-proBNP) serves as a valuable prognostic biomarker, its renal clearance may be accelerated in the presence of ARC, theoretically compromising its predictive accuracy. The present study aimed to quantify this “dilution effect” and construct an ARC-adjusted nomogram to optimize mortality prediction.Methods: This retrospective cohort study enrolled 352 patients with sTBI admitted to the Geriatrics ICU between June 2020 and June 2024. ARC defined as creatinine clearance > 130 mL/min/1.73 m2. Patients were stratified into ARC and Non-ARC cohorts. To mitigate baseline demographic confounders, propensity score matching (PSM) was employed. The primary endpoint was 28-day mortality. The impact of ARC on serum NT-proBNP concentrations and its subsequent prognostic value was evaluated using receiver operating characteristic (ROC) curves, logistic regression, and decision curve analysis (DCA). NT-proBNP values were log-transformed and included the continuous NRI value to quantify the incremental predictive power of the new model.Results: Within the original cohort, 141 patients (40.1%) exhibited ARC. In the matched cohort (n=186), patients with ARC demonstrated significantly lower serum NT-proBNP levels compared to the Non-ARC group (P=0.0089), suggesting a distinct biomarker dilution effect. Multivariate analysis identified ARC status as an independent protective factor for mortality, whereas elevated NT-proBNP persisted as a risk factor. Consequently, the predictive accuracy of NT-proBNP was markedly attenuated in the ARC group (AUC=0.637) relative to the Non-ARC group (AUC=0.833). A novel nomogram integrating ARC status, Age, log-NT-proBNP, APACHE II, and Hypertension was developed. This ARC-adjusted model exhibited improved risk stratification capabilities (continuous NRI=0.590) and yielded a higher net clinical benefit than the baseline model.Conclusion: ARC is associated with significantly depressed serum NT-proBNP levels in sTBI patients, suggesting a “dilution effect” driven by enhanced renal elimination. Clinicians should interpret NT-proBNP levels with caution in this population, as reliance on standard cutoff values may lead to an underestimation of mortality risk.Keywords: severe traumatic brain injury, augmented renal clearance, NT-proBNP, dilution effect, nomogram, prognosis