The Clinical View of Sepsis-Associated AKI: How Basic Science Can Help Solve This Problem

Area of Science:

• Critical care medicine
• Nephrology
• Translational research

Background:

• Sepsis-associated acute kidney injury (SA-AKI) is a major contributor to mortality globally.
• The complex nature of SA-AKI, including patient, pathogen, and treatment variability, impedes therapeutic advancements.
• Existing preclinical models often fail to fully capture human sepsis complexity, creating a translational gap.

Purpose of the Study:

• To highlight the need for improved preclinical models that better represent human sepsis.
• To emphasize the importance of acknowledging and addressing SA-AKI heterogeneity.
• To advocate for precision medicine approaches in SA-AKI treatment.

Main Methods:

• Review and synthesis of current understanding of SA-AKI pathogenesis and epidemiology.
• Analysis of the limitations of existing preclinical models in sepsis research.
• Discussion of precision medicine frameworks for developing targeted SA-AKI therapies.

Main Results:

• SA-AKI heterogeneity is a significant barrier to effective treatment development.
• Current preclinical models do not adequately reflect the complexities of human SA-AKI.
• Personalized therapeutic strategies are needed to improve SA-AKI outcomes.

Conclusions:

• Aligning preclinical models with human sepsis is crucial for advancing SA-AKI research.
• Embracing SA-AKI heterogeneity can lead to the identification of distinct, treatable endotypes.
• Developing mechanistically informed, personalized therapies holds promise for reducing the burden of SA-AKI.