Question: You are an expert researcher providing comprehensive, well-cited information.

Provide detailed information focusing on: 1. Key concepts and definitions with current understanding 2. Recent developments and latest research (prioritize 2023-2024 sources) 3. Current applications and real-world implementations 4. Expert opinions and analysis from authoritative sources 5. Relevant statistics and data from recent studies

Format as a comprehensive research report with proper citations. Include URLs and publication dates where available. Always prioritize recent, authoritative sources and provide specific citations for all major claims.

Disease Pathophysiology Research Template

Target Disease

• Disease Name: Hospital-Acquired Acute Kidney Injury
• MONDO ID: (if available)
• Category: Complex

Research Objectives

Please provide a comprehensive research report on the pathophysiology of Hospital-Acquired Acute Kidney Injury. Focus on the molecular and cellular mechanisms underlying disease progression.

Required Information

1. Core Pathophysiology

• What are the primary pathophysiological mechanisms?
• What molecular pathways are dysregulated?
• What cellular processes are affected?

2. Key Molecular Players

• Genes/Proteins: Which genes are causally involved or implicated?
• Chemical Entities: What metabolites, drugs, or small molecules are relevant?
• Cell Types: Which cell types are primarily affected?
• Anatomical Locations: Which tissues/organs are involved?

3. Biological Processes (for GO annotation)

• What biological processes (GO terms) are disrupted?
• Consider: signaling pathways, metabolic processes, cellular responses, transport, etc.

4. Cellular Components

• Where in the cell do key processes occur?
• Consider: organelles, membrane compartments, extracellular space, etc.

5. Disease Progression

• What is the sequence of events from initial trigger to clinical manifestation?
• Are there distinct stages or phases?

6. Phenotypic Manifestations

• What are the key clinical phenotypes?
• How do they relate to the underlying mechanisms?

Citation Requirements

• Cite primary literature (PMID preferred) for all mechanistic claims
• Prioritize recent reviews and landmark papers
• Include direct quotes where possible to support key statements

Output Format

Structure your response as a narrative that could be used to populate a disease knowledge base entry with: - Pathophysiology description - Gene/protein annotations with ontology terms (HGNC, GO) - Phenotype associations (HP terms) - Cell type involvement (CL terms) - Anatomical locations (UBERON terms) - Chemical entities (CHEBI terms) - Evidence items with PMIDs

Comprehensive Research Report: Hospital-Acquired Acute Kidney Injury (HA-AKI) Pathophysiology (Molecular/Cellular)

Target disease

• Disease name: Hospital-acquired acute kidney injury (HA-AKI; also termed in-hospital AKI, HAAKI)
• MONDO ID: Not consistently represented as a distinct MONDO entity in the retrieved sources; mechanistic evidence is largely for acute kidney injury broadly.
• Category: Complex, multifactorial syndrome occurring during hospitalization (e.g., ICU, ward, perioperative, sepsis, drug exposure).

1) Key concepts and definitions (current understanding)

1.1 Definition and case ascertainment

Hospital-acquired AKI is commonly operationalized as AKI that develops after hospital admission, often using an onset cutoff (e.g., >48 h) plus KDIGO creatinine/urine-output criteria; one ICU prospective cohort explicitly defined hospital-acquired AKI as AKI developing after 48 h (KDIGO creatinine-based) (https://doi.org/10.1038/s41598-024-79533-6; published Nov 2024) (havaldar2024epidemiologicalstudyof pages 1-2).

Large-scale hospital surveillance studies also distinguish AKI present at admission vs AKI peaking later during hospitalization, classifying “in-hospital” AKI by the time of peak creatinine after admission (https://doi.org/10.1093/ckj/sfae231; published Jul 2024) (esposito2024recognitionpatternsof pages 7-8).

1.2 Recognition gap as a core systems problem in HA-AKI

A major feature of HA-AKI is under-recognition in routine workflows. In a cohort of 56,820 hospitalized adults, serum-creatinine-defined AKI incidence was 24.5%, but most creatinine-defined cases lacked administrative documentation: 16.7% were “KDIGO-AKI” (AKI by creatinine but not coded) versus 3.3% “full-AKI” (meets creatinine criteria and coded), yielding ~68% undetection by discharge coding (https://doi.org/10.1093/ckj/sfae231; Jul 2024) (esposito2024recognitionpatternsof pages 1-2, esposito2024recognitionpatternsof pages 4-6).

This recognition gap matters because undetected AKI still associates with adverse outcomes (esposito2024recognitionpatternsof pages 1-2).

2) Core pathophysiology (molecular/cellular mechanisms)

HA-AKI is not a single disease entity; rather, it is a convergent clinical endpoint arising from overlapping insults (hemodynamic perturbations, infection/sepsis, nephrotoxins, hypoxia, surgery). Across settings, mechanistic convergence occurs at the level of:

2.1 Tubular epithelial stress/injury as a central node

Renal tubular epithelial cells (TECs)—particularly proximal tubules—are mitochondria-rich and metabolically demanding, and are highlighted as key vulnerable effectors in AKI (https://doi.org/10.1016/j.ebiom.2024.105294; published Sep 2024) (li2024renaltubularepithelial pages 1-2).

Adaptive repair after mild injury involves dedifferentiation, migration, proliferation, and redifferentiation; maladaptive repair links to failed regeneration and fibrosis. A schematic overview of these repair trajectories (resident progenitor vs scattered tubular cell phenotype, adaptive vs maladaptive repair leading to fibrosis) is provided in Figure 1 of Li et al. 2024 (li2024renaltubularepithelial media 407547cb).

2.2 Regulated cell-death programs in TECs (apoptosis, necroptosis, pyroptosis, ferroptosis, PANoptosis)

A 2024 eBioMedicine review synthesizes TEC death modalities as drivers of tubular damage and subsequent inflammation: - Apoptosis (caspase-mediated, comparatively non-inflammatory) (li2024renaltubularepithelial pages 2-3). - Necroptosis (RIPK-dependent, MLKL-mediated membrane rupture) promoting “necroinflammation,” immune activation, and impaired tubular regeneration (li2024renaltubularepithelial pages 2-3). - Pyroptosis (gasdermin pore formation) releasing DAMPs and inflammatory mediators (li2024renaltubularepithelial pages 2-3). - Ferroptosis (iron-dependent phospholipid peroxidation) emphasized as an important contributor across AKI models, with tubular-segment synchronized injury and protective effects of ferroptosis inhibition (li2024renaltubularepithelial pages 2-3, li2024renaltubularepithelial pages 11-12). - PANoptosis is described as an integrated program enabling simultaneous engagement of pyroptosis, apoptosis, and necroptosis via PANoptosome complexes (li2024renaltubularepithelial pages 1-2).

These death programs directly shape the inflammatory microenvironment of the kidney and influence whether repair is adaptive or fibrogenic (li2024renaltubularepithelial pages 2-3, li2024renaltubularepithelial media 407547cb).

2.3 Innate immune sensing and inflammasome-linked injury

In sepsis-associated contexts (a major HA-AKI driver), a contemporary view is that macro-hemodynamics and total renal blood flow may be preserved, while microcirculatory dysfunction and endothelial activation drive focal hypoxia and injury (https://doi.org/10.7759/cureus.75992; published Dec 2024) (aguilar2024sepsisassociatedacutekidney pages 2-4).

Key inflammatory processes described include cytokine release (e.g., TNF-α, IL-1, IL-6, IL-8), leukocyte adhesion, glycocalyx degradation, microvascular thrombosis, capillary shunting, and oxidative stress/mitochondrial dysfunction (aguilar2024sepsisassociatedacutekidney pages 2-4).

2.4 Mitochondrial dysfunction and metabolic reprogramming

A persistent mechanistic theme in AKI-to-AKD/CKD evolution is mitochondrial dysfunction, metabolic reprogramming, and cell-cycle arrest. A 2023 AKD overview emphasizes tubular epithelial cell-cycle arrest, chronic inflammation, mitochondrial dysfunction, failed regeneration, metabolic reprogramming, and RAS activation as mechanisms linking AKI to later subacute/chronic disease (https://doi.org/10.23876/j.krcp.23.001; published Nov 2023) (kung2023acutekidneydisease pages 1-3).

A TEC-focused synthesis also highlights mitophagy/biogenesis regulators and metabolic nodes (e.g., AMPK, PGC-1α-regulated pathways, and mitochondrial quality control) as important modulators of injury/repair balance (li2024renaltubularepithelial pages 16-16).

3) Key molecular players, cell types, anatomical locations, and chemical entities

3.1 Key genes/proteins (examples with strong mechanistic positioning in retrieved sources)

• Ferroptosis / redox: GPX4 (ferroptosis suppression), and system Xc− components discussed as protective via glutathione maintenance (li2024renaltubularepithelial pages 2-3, li2024renaltubularepithelial pages 1-2, li2024renaltubularepithelial pages 13-14).
• Necroptosis: RIPK1, RIPK3, MLKL as central executors of necroptotic membrane rupture and inflammatory amplification (li2024renaltubularepithelial pages 2-3, li2024renaltubularepithelial pages 13-14).
• Inflammasome / pyroptosis axis: NLRP3 (inflammasome activation) highlighted as a key inflammatory amplifier in TEC injury (li2024renaltubularepithelial pages 13-14, li2024renaltubularepithelial pages 16-16).
• Tubular injury biomarker-receptor: KIM-1 (HGNC: HAVCR1) appears as a TEC injury marker and also functions in phagocytosis/uptake-related contexts (li2024renaltubularepithelial pages 2-3, li2024renaltubularepithelial pages 16-16).
• Microcirculation / endothelial activation (process-level evidence): endothelial activation, leukocyte adhesion, glycocalyx degradation, and microthrombosis are emphasized in sepsis-AKI mechanisms (aguilar2024sepsisassociatedacutekidney pages 2-4).

3.2 Primary affected cell types (knowledge-base ready)

• Renal tubular epithelial cells (proximal tubule emphasized), as primary injury/repair executors (li2024renaltubularepithelial pages 1-2, li2024renaltubularepithelial media 407547cb).
• Endothelial cells / microvascular compartment driving regional hypoxia in sepsis-AKI contexts (aguilar2024sepsisassociatedacutekidney pages 2-4).
• Immune cells (neutrophils, macrophages, lymphocytes) as cytokine sources and effectors of inflammation and repair (aguilar2024sepsisassociatedacutekidney pages 2-4, li2024renaltubularepithelial pages 11-12).
• Pericytes / fibroblast lineage implicated in maladaptive repair and fibrosis during AKI-to-AKD transitions (kung2023acutekidneydisease pages 3-4).

3.3 Anatomical compartments

• Renal tubules (proximal tubule and thick ascending limb segments are highlighted in TEC-centric injury models) (li2024renaltubularepithelial pages 1-2).
• Renal microcirculation (glomerular and peritubular capillaries) as key sites of endothelial activation and perfusion heterogeneity in sepsis (aguilar2024sepsisassociatedacutekidney pages 2-4).
• Renal interstitium as a locus for inflammatory infiltration and later fibrogenesis (kung2023acutekidneydisease pages 3-4, li2024renaltubularepithelial pages 2-3).

3.4 Chemical entities and exposures relevant to HA-AKI

Nephrotoxic drugs and combinations are common hospital triggers. - In ICU HA-AKI, colistin exposure was identified as a risk factor in a prospective cohort (havaldar2024epidemiologicalstudyof pages 1-2). - In non-critical medical inpatients, predictors included type 2 diabetes and combined vancomycin + proton pump inhibitors, with mechanistic notes linking vancomycin to proximal tubular oxidative stress and PPIs to immune-mediated AIN-type mechanisms (https://doi.org/10.2147/IJNRD.S454987; published Apr 2024) (mekonnen2024hospitalacquiredacutekidney pages 6-8, mekonnen2024hospitalacquiredacutekidney pages 1-2). - In a hospitalized cohort of AKI cases managed by an AKI-nephrology team, drug-induced AKI (DI-AKI) accounted for 19.3% of AKI, with a mechanistic taxonomy: ATN (77%), AIN (15.2%), and crystal-induced nephropathy (2.6%); vancomycin was a leading nephrotoxin and associated with higher AKST and death (https://doi.org/10.3389/fmed.2024.1459170; published Oct 29, 2024) (garcia2024druginducedacutekidney pages 1-2, garcia2024druginducedacutekidney pages 2-3, garcia2024druginducedacutekidney pages 3-5).

4) Biological processes disrupted (GO-oriented)

Mechanistic evidence from recent reviews supports disruption of the following process categories: - Regulated cell death (apoptotic process; necroptotic process; pyroptotic process; ferroptotic process) (li2024renaltubularepithelial pages 2-3, li2024renaltubularepithelial pages 13-14). - Inflammatory response / innate immune signaling (cytokine-mediated signaling, inflammasome activation; leukocyte adhesion and endothelial activation in sepsis-associated settings) (aguilar2024sepsisassociatedacutekidney pages 2-4, li2024renaltubularepithelial pages 13-14). - Response to oxidative stress and lipid peroxidation (central to ferroptosis; ROS-linked injury) (li2024renaltubularepithelial pages 2-3, li2024renaltubularepithelial pages 1-2). - Mitochondrial organization / quality control and metabolic process regulation (mitochondrial dysfunction and metabolic reprogramming are emphasized as AKI-to-AKD mechanisms) (kung2023acutekidneydisease pages 1-3, li2024renaltubularepithelial pages 16-16). - Cell cycle arrest / DNA damage response (a key maladaptive repair mechanism in AKD framing) (kung2023acutekidneydisease pages 1-3). - Extracellular matrix organization / fibrogenesis (pericyte-to-myofibroblast transition; epigenetic maintenance of profibrotic state) (kung2023acutekidneydisease pages 3-4).

5) Cellular components (where key processes occur)

• Mitochondria: central to TEC vulnerability, ROS generation, apoptosis initiation, and quality-control pathways (li2024renaltubularepithelial pages 1-2, li2024renaltubularepithelial pages 16-16).
• Plasma membrane: decisive in necroptosis/pyroptosis (rupture or pore formation) and ferroptosis (phospholipid peroxidation-driven membrane failure) (li2024renaltubularepithelial pages 2-3, li2024renaltubularepithelial pages 1-2).
• Cytosol: inflammasome assembly (NLRP3 axis) and necroptotic signaling complexes (li2024renaltubularepithelial pages 13-14).
• Microvascular luminal surface / endothelial glycocalyx: key site of sepsis-associated microcirculatory dysfunction and permeability changes (aguilar2024sepsisassociatedacutekidney pages 2-4).

6) Disease progression (sequence of events; stages/phases)

6.1 Trigger → early injury phase

Common inpatient triggers include infection/sepsis, hemodynamic instability, mechanical ventilation-related physiology, chloride/fluid perturbations, and nephrotoxic drug exposure (havaldar2024epidemiologicalstudyof pages 1-2, mekonnen2024hospitalacquiredacutekidney pages 6-8).

In sepsis-associated contexts, a key modern concept is that injury can occur despite preserved renal blood flow, via microcirculatory/endothelial dysfunction causing regional hypoxia plus inflammatory/oxidative injury (aguilar2024sepsisassociatedacutekidney pages 2-4).

6.2 Injury amplification and clinical syndrome

Tubular cell injury engages regulated cell-death programs (ferroptosis, necroptosis, pyroptosis, apoptosis/PANoptosis), propagating necroinflammation and functional GFR decline (li2024renaltubularepithelial pages 2-3, li2024renaltubularepithelial pages 1-2).

6.3 Recovery vs maladaptive repair (AKI → AKD window)

If repair is incomplete, the 7–90-day period termed acute kidney disease (AKD) provides a mechanistic bridge to CKD, with drivers including cell-cycle arrest, epigenetic reprogramming, chronic inflammation, mitochondrial dysfunction, failed regeneration, and RAS activation (kung2023acutekidneydisease pages 1-3, kung2023acutekidneydisease pages 3-4).

6.4 Timing distinctions (clinically important in HA-AKI)

In hospitalized cohorts, AKI that peaks later during admission (“in-hospital AKI”) is associated with worse outcomes than AKI present at admission. In one large cohort, in-hospital AKI had longer LOS (mean 26.6 vs 18.7 days) and higher in-hospital mortality (30.7% vs 13.8%) compared with admission AKI (esposito2024recognitionpatternsof pages 7-8).

In septic AKI, later-developing AKI is also linked to higher mortality than early/transient AKI; a 2024 review states: “the development of AKI later during an episode of sepsis has been associated with worse clinical outcomes and increased mortality rates (76.5% compared with 61.5% in early AKI)” (https://doi.org/10.7759/cureus.75992; Dec 2024) (aguilar2024sepsisassociatedacutekidney pages 10-11).

7) Phenotypic manifestations (HP-oriented)

Mechanistically, HA-AKI manifests clinically as acute reductions in filtration and tubular function, often captured by: - Rising serum creatinine / azotemia (used for epidemiologic ascertainment in multiple studies) (esposito2024recognitionpatternsof pages 4-6, havaldar2024epidemiologicalstudyof pages 1-2). - Need for kidney replacement therapy (KRT/RRT) in severe cases; ICU HA-AKI cohort reported 15.9% required RRT during hospitalization (havaldar2024epidemiologicalstudyof pages 1-2). - In-hospital mortality and prolonged stay. ICU HA-AKI cohort mortality was 43.18% vs 14.41% without AKI (havaldar2024epidemiologicalstudyof pages 1-2).

8) Recent developments (2023–2024 emphasis): statistics, biomarkers, and implementation science

8.1 Epidemiology and outcomes in hospital settings (recent data)

• ICU prospective cohort (2018–2023 enrollment window; published Nov 2024): HA-AKI incidence 16.11% among ICU patients without AKI on admission; hospital mortality 43.18% with HA-AKI; 15.90% required RRT (https://doi.org/10.1038/s41598-024-79533-6) (havaldar2024epidemiologicalstudyof pages 1-2).
• Large hospitalized cohort (published Jul 2024): overall AKI incidence 24.5%; ICU incidence 59%; ~68% of creatinine-defined AKI was not coded/documented (“KDIGO-AKI”) (https://doi.org/10.1093/ckj/sfae231) (esposito2024recognitionpatternsof pages 4-6, esposito2024recognitionpatternsof pages 1-2).
• Non-critical medical cohort (published Apr 2024): HA-AKI incidence density 6.0 per 100 person-days; predictors included T2DM and vancomycin/PPI exposure (https://doi.org/10.2147/IJNRD.S454987) (mekonnen2024hospitalacquiredacutekidney pages 1-2).

8.2 Biomarkers and risk stratification (real-world relevance)

Biomarkers are increasingly used to move from “late functional change” (creatinine/urine output) toward earlier “stress/injury” signals.

• [TIMP-2]·[IGFBP7] + furosemide stress test (FST) to enrich for early RRT need in sepsis-AKI (prospective multicenter; published Jul 2024). In 100 sepsis patients with AKI stage ≥2, 32% required RRT within 7 days. A two-step workflow (FST screen → [TIMP-2]·[IGFBP7] at 2 h) improved prediction accuracy to 0.83 with specificity 0.96 and PPV 0.86 (https://doi.org/10.1186/s13613-024-01349-4) (palmowski2024predictiveenrichmentfor pages 1-2).

• CCL14 vs [TIMP-2]·[IGFBP7] for predicting renal non-recovery in sepsis-AKI (prospective observational; published May 2024): For 7-day non-recovery prediction, CCL14 AUC 0.901 vs [TIMP-2]·[IGFBP7] AUC 0.730, with reported cutoffs and operating characteristics (https://doi.org/10.1186/s12882-024-03589-9) (nephrology2024predictiveperformanceof pages 7-8).

8.3 Hospital implementation: electronic alerts and care bundles

Electronic AKI alerting systems and linked order sets are widely implemented but show heterogeneous outcome effects.

• Order set / care-bundle use with alerting (single-center cohort; published Feb 2024): An EHR-integrated AKI order set was used in 9.8% of AKI events and was associated with lower all-cause mortality (multivariable OR 0.72, 95% CI 0.57–0.91) and increased likelihood of AKI-stage improvement (multivariable OR 4.27, 95% CI 3.54–5.14), though LOS was longer when used (https://doi.org/10.1080/0886022X.2024.2313177) (chenxu2024impactofelectronic pages 1-2).

• RCT-only evidence for alerts (meta-analysis; published Sep 2024): Across six RCTs (n=40,146), e-alerts showed no mortality benefit (RR 1.02), no reduction in creatinine or AKI progression, but increased dialysis (RR 1.14) and increased documentation (RR 1.21) (https://doi.org/10.1186/s12916-024-03639-x) (fu2024effectofelectronic pages 1-2).

• Broader mixed-design synthesis (systematic review/meta-analysis; 2024): pooled estimates suggested modest AKI progression reduction (RR 0.91) but unclear mortality benefit and increased dialysis (RR 1.16) (chen2024electronicalertsystems pages 6-7).

Interpretation: The collective evidence supports the view that alerts improve recognition/documentation, but clinical outcome improvements require coupling alerts with actionable responses (order sets, care bundles, nephrology/pharmacy workflows) (chenxu2024impactofelectronic pages 1-2, fu2024effectofelectronic pages 1-2).

9) Expert opinions and analysis (from authoritative sources in retrieved set)

9.1 Sepsis-AKI microcirculation paradigm

A key expert framing from a 2024 review is that sepsis-AKI is not simply “low renal blood flow,” but a syndrome in which endothelial activation and microcirculatory dysfunction can create patchy ischemia/hypoxia even when global renal flow is preserved (aguilar2024sepsisassociatedacutekidney pages 2-4).

9.2 AKI as a continuum into AKD/CKD (window for intervention)

A 2023 synthesis emphasizes AKD (7–90 days) as a clinically important period where persistent tubular injury, cell-cycle arrest, epigenetic changes, and metabolic dysfunction can drive progression to CKD, motivating structured follow-up and recurrence prevention (kung2023acutekidneydisease pages 1-3).

10) Knowledge-base ready annotation blocks

10.1 Pathophysiology description (narrative)

Hospital-acquired AKI results from convergent inpatient insults (sepsis/inflammation, microvascular dysfunction, nephrotoxins, ventilation/hemodynamic perturbations) that converge on renal tubular epithelial stress. TEC injury triggers regulated death programs (ferroptosis, necroptosis, pyroptosis, apoptosis/PANoptosis) and mitochondrial/metabolic dysfunction, amplifying inflammation and impairing epithelial repair. Microcirculatory endothelial activation and glycocalyx injury (especially in sepsis) create regional hypoxia and immune-thrombotic injury. Outcomes depend on whether repair is adaptive (successful redifferentiation and recovery) or maladaptive (cell-cycle arrest, persistent inflammation, epigenetic profibrotic programs and pericyte-to-myofibroblast transition), promoting AKD and long-term CKD risk (li2024renaltubularepithelial pages 2-3, aguilar2024sepsisassociatedacutekidney pages 2-4, kung2023acutekidneydisease pages 3-4, li2024renaltubularepithelial media 407547cb).

10.2 Candidate gene/protein annotations (examples)

• HAVCR1 (KIM-1): tubular injury marker and phagocytic receptor context in TEC apoptosis/injury response (li2024renaltubularepithelial pages 2-3).
• GPX4: ferroptosis suppressor implicated in TEC ferroptosis biology (li2024renaltubularepithelial pages 13-14, li2024renaltubularepithelial pages 16-16).
• RIPK1/RIPK3/MLKL: necroptosis machinery linked to inflammatory tubular damage (li2024renaltubularepithelial pages 13-14).
• NLRP3: inflammasome node linking stress signals to inflammatory injury programs (li2024renaltubularepithelial pages 13-14, li2024renaltubularepithelial pages 16-16).

10.3 Cell type involvement (examples)

• Tubular epithelial cell (proximal tubule emphasized) (li2024renaltubularepithelial pages 1-2).
• Endothelial cell / microvascular unit in sepsis-AKI (aguilar2024sepsisassociatedacutekidney pages 2-4).
• Macrophage (dual roles across injury/repair stages) (li2024renaltubularepithelial pages 11-12).

10.4 Anatomical locations (examples)

• Renal tubules (proximal tubule segments; tubular cast formation noted in TEC-injury context) (li2024renaltubularepithelial pages 1-2).
• Renal microcirculation (endothelial activation and shunting in sepsis) (aguilar2024sepsisassociatedacutekidney pages 2-4).
• Renal interstitium (inflammation/fibrosis in maladaptive repair) (kung2023acutekidneydisease pages 3-4).

10.5 Chemical entities (examples)

• Vancomycin and PPIs as HA-AKI risk exposures in non-critical inpatients and DI-AKI cohorts (mekonnen2024hospitalacquiredacutekidney pages 6-8, garcia2024druginducedacutekidney pages 3-5).
• Colistin as an ICU HA-AKI risk factor (havaldar2024epidemiologicalstudyof pages 1-2).

11) Evidence tables and figures

Table: This table summarizes the core pathophysiological domains of HA-AKI, detailing key pathways, molecular players, affected cell types, and anatomical sites, along with associated chemical entities and supporting evidence from recent literature.

A schematic figure summarizing adaptive vs maladaptive TEC repair trajectories (Figure 1, Li et al. 2024) is available (li2024renaltubularepithelial media 407547cb).

12) Limitations of the evidence base retrieved here

• PMIDs were not present in the full-text excerpts retrieved for most 2023–2024 papers, so citations here use DOI + publication month/year from the papers themselves (aguilar2024sepsisassociatedacutekidney pages 2-4, li2024renaltubularepithelial pages 1-2, havaldar2024epidemiologicalstudyof pages 1-2). A PubMed lookup step would be required to attach PMIDs systematically.
• Some mechanistic themes (e.g., STING/ER stress axis) are represented in the retrieved corpus primarily through sepsis-focused materials rather than HA-AKI-specific cohorts; nevertheless, sepsis is a major HA-AKI etiology in hospital settings (havaldar2024epidemiologicalstudyof pages 1-2, aguilar2024sepsisassociatedacutekidney pages 2-4).

Key source URLs (most used, 2023–2024)

• Esposito et al., Clinical Kidney Journal (Jul 2024): https://doi.org/10.1093/ckj/sfae231 (esposito2024recognitionpatternsof pages 1-2, esposito2024recognitionpatternsof pages 4-6)
• Havaldar et al., Scientific Reports (Nov 2024): https://doi.org/10.1038/s41598-024-79533-6 (havaldar2024epidemiologicalstudyof pages 1-2)
• Li et al., eBioMedicine (Sep 2024): https://doi.org/10.1016/j.ebiom.2024.105294 (li2024renaltubularepithelial pages 1-2, li2024renaltubularepithelial media 407547cb)
• Palmowski et al., Annals of Intensive Care (Jul 2024): https://doi.org/10.1186/s13613-024-01349-4 (palmowski2024predictiveenrichmentfor pages 1-2)
• Fu et al., BMC Medicine (Sep 2024): https://doi.org/10.1186/s12916-024-03639-x (fu2024effectofelectronic pages 1-2)
• Garcia et al., Frontiers in Medicine (Oct 2024): https://doi.org/10.3389/fmed.2024.1459170 (garcia2024druginducedacutekidney pages 3-5)
• Mekonnen et al., IJNRD (Apr 2024): https://doi.org/10.2147/IJNRD.S454987 (mekonnen2024hospitalacquiredacutekidney pages 1-2)
• Kung & Chou, Kidney Research and Clinical Practice (Nov 2023): https://doi.org/10.23876/j.krcp.23.001 (kung2023acutekidneydisease pages 1-3)

References

1. (havaldar2024epidemiologicalstudyof pages 1-2): Amarja Ashok Havaldar, E.A. Chinny Sushmitha, Sahad Bin Shrouf, Monisha H. S., Madhammal N., and Sumithra Selvam. Epidemiological study of hospital acquired acute kidney injury in critically ill and its effect on the survival. Scientific Reports, Nov 2024. URL: https://doi.org/10.1038/s41598-024-79533-6, doi:10.1038/s41598-024-79533-6. This article has 12 citations and is from a peer-reviewed journal.

2. (esposito2024recognitionpatternsof pages 7-8): Pasquale Esposito, Francesca Cappadona, Marita Marengo, Marco Fiorentino, Paolo Fabbrini, Alessandro Domenico Quercia, Francesco Garzotto, Giuseppe Castellano, Vincenzo Cantaluppi, and Francesca Viazzi. Recognition patterns of acute kidney injury in hospitalized patients. Clinical Kidney Journal, Jul 2024. URL: https://doi.org/10.1093/ckj/sfae231, doi:10.1093/ckj/sfae231. This article has 15 citations and is from a peer-reviewed journal.

3. (esposito2024recognitionpatternsof pages 1-2): Pasquale Esposito, Francesca Cappadona, Marita Marengo, Marco Fiorentino, Paolo Fabbrini, Alessandro Domenico Quercia, Francesco Garzotto, Giuseppe Castellano, Vincenzo Cantaluppi, and Francesca Viazzi. Recognition patterns of acute kidney injury in hospitalized patients. Clinical Kidney Journal, Jul 2024. URL: https://doi.org/10.1093/ckj/sfae231, doi:10.1093/ckj/sfae231. This article has 15 citations and is from a peer-reviewed journal.

4. (esposito2024recognitionpatternsof pages 4-6): Pasquale Esposito, Francesca Cappadona, Marita Marengo, Marco Fiorentino, Paolo Fabbrini, Alessandro Domenico Quercia, Francesco Garzotto, Giuseppe Castellano, Vincenzo Cantaluppi, and Francesca Viazzi. Recognition patterns of acute kidney injury in hospitalized patients. Clinical Kidney Journal, Jul 2024. URL: https://doi.org/10.1093/ckj/sfae231, doi:10.1093/ckj/sfae231. This article has 15 citations and is from a peer-reviewed journal.

5. (li2024renaltubularepithelial pages 1-2): Zuo-Lin Li, Xin-Yan Li, Yan Zhou, Bin Wang, Lin-Li Lv, and Bi-Cheng Liu. Renal tubular epithelial cells response to injury in acute kidney injury. eBioMedicine, 107:105294, Sep 2024. URL: https://doi.org/10.1016/j.ebiom.2024.105294, doi:10.1016/j.ebiom.2024.105294. This article has 93 citations and is from a peer-reviewed journal.

6. (li2024renaltubularepithelial media 407547cb): Zuo-Lin Li, Xin-Yan Li, Yan Zhou, Bin Wang, Lin-Li Lv, and Bi-Cheng Liu. Renal tubular epithelial cells response to injury in acute kidney injury. eBioMedicine, 107:105294, Sep 2024. URL: https://doi.org/10.1016/j.ebiom.2024.105294, doi:10.1016/j.ebiom.2024.105294. This article has 93 citations and is from a peer-reviewed journal.

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