Augmented renal clearance: from pathophysiological mechanisms to clinical implications and research perspectives

OBJECTIVES: Augmented renal clearance (ARC) is a critical clinical phenomenon characterized by altered renal excretory function in patients. Although ARC has garnered growing clinical and research attention in recent years, notable gaps remain in its investigation. Inadequate recognition of ARC-related risks may lead to underappreciation of this clinically significant condition in practice. This narrative review synthesizes current evidence on ARC. METHODS: Current evidence on ARC was narratively reviewed, including pathophysiological hypotheses, diagnostic criteria, predictive models, drug-dosing implications and emerging monitoring techniques. Compared with earlier summaries, we place particular emphasis on recent changes in kidney-function assessment for drug dosing, including the distinction between measured glomerular filtration rate (GFR), measured creatinine clearance (CrCl), Cockcroft-Gault estimated CrCl, and contemporary estimated GFR equations. RESULTS: We discuss the limitations of predictive equations in unstable kidney function, the potential role of repeated short-interval CrCl, bedside hemodynamic assessment, standardized experimental models and multi-omics approaches. CONCLUSIONS: ARC should be regarded as a dynamic pharmacokinetic phenotype requiring timely recognition, drug-specific interpretation, therapeutic drug monitoring and direct or repeated assessment of renal clearance in high-risk patients.