Acute kidney injury over the past decade: from definition evolution to pathogenesis insights and innovative therapeutic strategies

TL;DR

This paper reviews AKI's global impact, evolving definitions, pathogenesis, and new diagnostic and therapeutic approaches over the past decade.

Contribution

The paper provides updated insights into AKI's molecular mechanisms and innovative therapies, including AI and stem cell-based strategies.

Findings

Single-cell sequencing has revealed key molecular pathways and therapeutic targets in AKI.

Urinary biomarkers and AI-driven models show promise for early AKI detection.

Emerging therapies like mesenchymal stem cells and ferroptosis inhibitors may improve renal repair.

Abstract

Acute kidney injury (AKI) is a major global health concern affecting approximately 13.3 million individuals annually and contributing to 1.7 million deaths, with disproportionately high incidence in low- and middle-income countries, children, and critically ill patients. Its complex pathogenesis centers on regulated cell death(RCD) (apoptosis, pyroptosis, necroptosis, ferroptosis, cuproptosis), inflammation, DNA damage, and metabolic disorders, and recent advances in single-cell sequencing have uncovered key molecular pathways and therapeutic targets. Early diagnosis is pivotal for preventing progression to chronic kidney disease (CKD), yet delays remain a major barrier to improved outcomes. The evolving definition—from acute renal failure (ARF) to AKI and the recent proposal of acute kidney disease (AKD)—has enhanced identification of renal dysfunction, facilitating timely intervention. AKI is classified into prerenal, intrinsic renal, and postrenal types, with subdivisions including sepsis-induced and drug-induced variants. Innovative diagnostic tools, such as urinary biomarkers (TIMP-2, IGFBP7, NGAL, KIM-1), non-coding RNAs, advanced imaging, and AI-driven models, offer promise for early detection, though standardization and biomarker validation challenges persist. Current treatments are largely supportive, but emerging therapies—including mesenchymal stem cell therapies, traditional Chinese medicine, anti-inflammatory agents, and ferroptosis inhibitors—show potential for renal repair. Future directions emphasize the Acute Disease Quality Initiative’s digital AKI management model, integrating AI-enabled dynamic monitoring and multilevel, integrated care to optimize volume management and improve patient outcomes.

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