Diagnostic Biomarkers and Metabolic Mechanisms of Polymyxin B-Induced Acute Kidney Injury Revealed by Integrated Mass Spectrometry
Abstract
Abstract Background The clinical utility of polymyxin B (PB), a last-resort antibiotic for multidrug-resistant Gram-negative infections, is severely compromised by acute kidney injury (AKI). However, both early diagnostic approaches and the mechanistic understanding of PB-induced AKI remain limited. To address these gaps, we conducted a large-scale study in a clinical cohort and a rat model using an integrated analytical approach. Methods We conducted the first integrated mass spectrometry analysis of 83 patients receiving PB-based regimens (60 non-AKI cases and 23 AKI cases), with longitudinal plasma samples collected (n = 207). Key findings were validated across species using male Sprague-Dawley rats. Targeted quantification of plasma polymyxin B1 (PB1), PB2, PB3, isoleucine-polymyxin B1 (ILE-PB1), and PB6 was performed using ultra-performance liquid chromatography coupled with high-resolution mass spectrometry (UPLC-HRMS), alongside spatial mapping of their renal distribution using airflow-assisted desorption electrospray ionization-mass spectrometry imaging (AFADESI-MSI); and metabolite alterations were profiled via untargeted metabolomics. Multivariable logistic regression models were constructed, and the area under the receiver operating characteristic curve (AUC) was used to evaluate their diagnostic performance. Results A therapeutic drug monitoring panel of PB1, PB2, PB3, and ILE-PB1 improved risk stratification over the conventional index (AUC 0.703 vs. 0.561).…
How strong is the evidence?
Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 207 participants or records.
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