Iron Biology in Acute Kidney Injury: Catalytic Iron, Hepcidin-Ferroportin Axis, and NGAL-A Narrative Review

Dysregulated iron handling-including catalytic iron and ferroptosis, hepcidin-ferroportin signaling, ferritin dynamics, and neutrophil gelatinase-associated lipocalin (NGAL)-mediated siderophore transport-has been implicated in the initiation and propagation of acute kidney injury (AKI) across ischemia-reperfusion, sepsis, and nephrotoxic contexts. To provide a SANRA-aligned narrative synthesis of mechanistic and translational evidence on iron biology in AKI, clarifying biomarker readiness and therapeutic prospects while explicitly separating preclinical from human findings. PubMed, Scopus, and Web of Science (1 January 2000 to 30 September 2025), plus appraised grey literature (guidelines/registries) using predefined criteria (authority, update recency, and methodological transparency). Narrative review with comprehensive database searches, single-reviewer screening/extraction (acknowledged as a limitation), and qualitative synthesis. Evidence is organized by pathway (catalytic iron/ferroptosis, transferrin (Tf)/transferrin receptor (/TfR), ferritin/ferritin heavy chain (FtH), hepcidin-ferroportin and NGAL) and translational domain (biomarkers and therapeutics). Statements are tagged as [Preclinical] or [Human]. [Preclinical] Robust signals support roles for catalytic iron and ferroptosis, protection by iron chelation, hepcidin modulation, heme oxygenase 1 (HO-1)/FtH induction, and apotransferrin/NGAL-based strategies. [Human] Biomarkers such as NGAL show clinical utility for kidney injury detection, whereas catalytic iron assays (labile plasma iron [LPI]/bleomycin-detectable iron [BDI]) remain investigational with limited standardization. Observational links between iron-regulatory pathways and AKI risk exist, but interventional trials are sparse; dose, timing, and safety of iron-targeted strategies in defined AKI settings remain to be established. Iron-handling pathways are compelling targets for AKI prevention/mitigation, yet high-quality human trials are limited. Priorities include standardized catalytic-iron assays, biomarker-guided enrichment, and pragmatic trials of tractable interventions (e.g., peri-contrast or cardiopulmonary bypass settings). Until such evidence accumulates, recommendations beyond standard care should be avoided.