Hallmarks of acute kidney injury: molecular endotypes, precision phenotyping, and phase-adapted therapy.

Authors

Hongtu Hu, Zikang Liu, Rui Ji, Yinghui Huang

Published in

EBioMedicine. Volume 131. Pages 106436. Aug 15, 2026. Epub Aug 15, 2026.

Abstract

Acute kidney injury (AKI) is a heterogeneous syndrome for which creatinine and urine output incompletely represent underlying biology and temporal evolution. We organise AKI pathophysiology into four interconnected dimensions: initiation and effector injury; cell fate and immune microenvironment; repair and outcome determination; and systemic integration. These dimensions encompass microvascular and metabolic failure, oxidative injury, regulated cell death, inflammation, adaptive and maladaptive repair, senescence, fibrosis, and organ crosstalk. We translate these hallmarks into measurable phenotypes using biomarkers, imaging, and functional tests, and propose an aetiological trigger-hallmarks-phase (E-H-P) framework linking cause, dominant biology, and disease phase. Practical examples illustrate how E-H-P phenotyping can complement conventional staging and support trial enrichment. We distinguish established supportive care from investigational mechanism-directed therapies and identify priorities for biomarker validation, phase-specific intervention, and prevention of AKI-to-CKD transition.

PMID:
42603515
Bibliographic data and abstract were imported from PubMed on 16 Aug 2026.

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