Acute Kidney Injury-to-Chronic Kidney Disease Transition: Clinical Evidence, Pathophysiologic Mechanisms, and Emerging Role of Traditional Chinese Medicine.

Abstract

Acute kidney injury (AKI) is common in hospitalized patients and is strongly associated with subsequent acute kidney disease (AKD), chronic kidney disease (CKD), end-stage kidney disease, and increased mortality. The Kidney Disease: Improving Global Outcomes 2026 AKI/AKD public review draft emphasizes the AKI-AKD-CKD continuum and the need for structured follow-up, kidney function and proteinuria reassessment, and risk stratification after AKI or AKD. Mechanistically, the AKI-to-CKD transition is driven by maladaptive tubular repair, characterized by G2/M arrest and sustained profibrotic signaling, microvascular rarefaction-induced hypoxia, mitochondrial dysfunction with impaired fatty acid oxidation, and amplification of injury by regulated cell death pathways, including ferroptosis and necroptosis, in concert with chronic inflammation. Cellular senescence in tubular epithelial cells and immune cells further perpetuates a senescence-associated secretory phenotype-mediated proinflammatory and profibrotic milieu, thereby promoting irreversible fibrosis. Effective targeted therapies remain lacking. Traditional Chinese medicine-derived agents may provide mechanistically plausible multitarget candidates for modulating tubular injury and interstitial fibrosis.