The AKI-CKD Continuum: Mechanisms and Therapeutic Interventions

Area of Science:

• Nephrology
• Molecular Biology
• Pathophysiology

Background:

• Acute kidney injury (AKI) frequently progresses to chronic kidney disease (CKD), indicating a failure to address the dynamic continuum.
• Recognizing the distinct phases of AKI progression to CKD is crucial for effective intervention.

Purpose of the Study:

• To synthesize emerging evidence on the mechanistic phases of the AKI-to-CKD continuum.
• To identify universal processes driving fibrosis across these phases.
• To propose a temporally informed, multi-phase therapeutic strategy.

Main Methods:

• Review of emerging evidence on AKI-to-CKD progression.
• Analysis of distinct mechanistic phases and universal integrating processes.
• Identification of temporal variability in cellular contexts and substrate availability.

Main Results:

• The AKI-to-CKD continuum unfolds in four distinct phases: hyperacute injury, persistent AKI, acute kidney disease (AKD), and CKD.
• Universal mechanisms include epigenetic injury memory, metabolic reprogramming, and renal functional reserve.
• Phase-agnostic treatments are ineffective due to temporally variable molecular environments.

Conclusions:

• A temporally informed, multi-phase strategy targeting universal mechanisms at optimal windows is essential.
• This approach is crucial for preventing or attenuating irreversible AKI-to-CKD progression and renal fibrosis.
• Understanding the dynamic nature of AKI-to-CKD is vital for developing effective therapeutic interventions.