Polymyxin-associated acute kidney injury management requires reduced nephrotoxic exposure and enhanced monitoring

Polymyxins are critical 'last-line' antibiotics for severe Gram-negative bacterial infections, especially in critically ill patients battling multidrug-resistant pathogens. Despite their efficacy, polymyxin-associated acute kidney injury (PA-AKI) is a significant dose-limiting toxicity, often necessitating treatment discontinuation or dose reduction. Understanding the pathophysiology and identifying modifiable risk factors for PA-AKI is crucial to optimize polymyxin therapy and improve patient outcomes, addressing a key gap in current clinical practice.

This comprehensive review synthesized current knowledge regarding the pathophysiology, risk factors, and clinical management of polymyxin-associated acute kidney injury (PA-AKI). The authors examined existing literature to provide updated perspectives on preventing and treating this adverse event. They focused on identifying established and emerging strategies, including monitoring protocols and potential biomarkers, to guide clinicians in optimizing polymyxin use while minimizing nephrotoxicity.

The review underscores that reducing exposure to concomitant nephrotoxic agents is paramount in preventing PA-AKI. Timely and standardized monitoring of serum creatinine, urine volume, and polymyxin concentrations plays a key role in mitigating the risk and progression of PA-AKI. While several biomarkers show promise for early prediction of PA-AKI, enabling earlier intervention, the authors note that many of these have not yet undergone extensive clinical validation. There is a clear need to integrate real-world evidence into clinical practice guidelines for polymyxin use to enhance their safety profile. Further research is recommended to identify genetic risk factors for PA-AKI and to develop novel polymyxin analogues with reduced nephrotoxicity. This comprehensive approach aims to balance the critical need for polymyxins with the imperative to minimize kidney damage.

Reducing exposure to concomitant nephrotoxic agents, together with timely and standardized monitoring of serum creatinine, urine volume and polymyxin concentrations, plays a key role in mitigating the risk and progression of PA-AKI.