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Molecular mechanisms and therapeutic interventions in acute kidney injury: a literature review

BMC Nephrology volume 26, Article number: 144 (2025) Cite this article

Abstract

Acute kidney injury (AKI) is a clinical challenge characterized by elevated morbidity and a substantial impact on individual health and socioeconomic factors. A comprehensive examination of the molecular pathways behind AKI is essential for its prevention and management. In recent years, vigorous research in the domain of AKI has concentrated on pathophysiological characteristics, early identification, and therapeutic approaches across many aetiologies and highlighted the principal themes of oxidative stress, inflammatory response, apoptosis, necrosis, and immunological response. This review comprehensively reviewed the molecular mechanisms underlying AKI, including oxidative stress, inflammatory pathways, immune cell-mediated injury, activation of the renin-angiotensin-aldosterone (RAAS) system, mitochondrial damage and autophagy, apoptosis, necrosis, etc. Inflammatory pathways are involved in the injuries in all four structural components of the kidney. We also summarized therapeutic techniques and pharmacological agents associated with the aforementioned molecular pathways. This work aims to clarify the molecular mechanisms of AKI thoroughly, offer novel insights for further investigations of AKI, and facilitate the formulation of efficient therapeutic methods to avert the progression of AKI.

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Introduction

Acute kidney injury (AKI) refers to the sudden damage to the renal parenchyma or sharp decline in kidney function, resulting from a range of factors with diverse underlying mechanisms. AKI can be broadly categorized into pre-renal AKI, which is centered on decreased glomerular filtration rate (GFR) due to decreased renal perfusion, and post-renal AKI, which is centered on urinary tract obstruction. The rest are renal AKI in which the structures of the nephron, such as glomeruli, tubules, vasculature, and renal tubules are affected (Table 1) [1]. AKI is a heavy health burden worldwide, with a global incidence of approximately 21.6% and 33.7% in adults and children, respectively, and an overall mortality rate of 23.9% and 13.8% in adults and children in 2013 [2]. AKI is significantly associated with in-hospital adverse events and progression to chronic kidney disease (CKD) and greatly increases the risk of long-term morbidity and mortality [3,4,5].

Although the clinical significance of AKI is widely recognized, there is still a lack of specific therapeutic options for AKI so far. Diverse molecular mechanisms have been reported to contribute to the parenchymal damage of kidneys in AKI, including complement activation [6], oxidative stress [7], and inflammation [7, 8]. Delving into these molecular mechanisms underlying the pathological processes of AKI is an important approach to identify specific biomarkers and potential therapeutic targets.

Here in this review, we summarized the molecular mechanisms and corresponding interventions of AKI in the literature, aiming to comprehensively and thoroughly understand the pathogenic molecular mechanisms of AKI and to provide assistance for future research on specific prevention and treatment strategies for AKI. For ease of description, the molecular mechanisms are summarized based on the four main components of the kidney, the glomeruli, tubules, vasculature, and interstitium. Interventions for individual mechanisms are also presented.

Table 1 Types of AKI
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Underlying molecular mechanisms of glomerular injury in AKI

Immune complex deposition

Glomeruli are susceptible to commonly affected by injury caused by deposition of immune complexes in systemic immune and autoimmune disorders [9, 10]. Deposited immune complexes stimulate circulating immune cells, which subsequently release cytokines and vasoactive substances, creating a pro-inflammatory milieu after the deposition of immune complexes [11]. In IgA nephropathy, stimulatory circulating immune complexes containing galactose-deficient Immunoglobulin A1 induced the production of transforming growth factor-beta (TGF-β), which stimulated the production of extracellular matrix (ECM) proteins and promoted the synthesis of laminin, leading to the proliferation of mesangial cells [12].

Immune complexes activate complement via the classical pathway and have been reported in various types of glomerulonephritis [13], leading to damage to glomerular capillary walls, glomerular basement membrane, and other structures and inflammatory cell recruitment [14]. Complement Component 3a (C3a) and Complement Component 5a (C5a) formed by complement activation have potent proinflammatory functions and create the membrane attack complex (MAC) that can induce cell activation or lysis [15]. Activation of the complement system forms the C5a-C5a receptor1 axis to promote podocyte injury and disrupt the glomerular filtration barrier by enhancing Dynamin-related protein 1-mediated mitochondrial fission [16].

Activation of renin-angiotensin-aldosterone system (RAAS)

Reduced renal blood flow, particularly in the presence of pre-renal AKI, results in a diminished GFR, prompting para-glomerular cells to secrete increased amounts of renin, activating the RAAS system. Prolonged activation of the RAAS results in renal hypoxia, vasoconstriction, glomerulosclerosis, and glomerular interstitial fibrosis [17]. Angiotensin II (AngII) induces glomerulosclerosis through the upregulation of TGF-β in rat renal cells, leading to enhanced production of ECM proteins [18]. AngII has also been shown to enhance the expression of toll-like receptor 4 (TLR4), which in turn activates nuclear factor-kappa B (NF-κB) in mesangial cells, amplifying the inflammatory response [19]. Moreover, hyperactivation of RAAS promotes oxidative stress to exacerbate kidney damage [20]. Research indicates that angiotensin-converting enzyme inhibitors and AngII receptor blockers are associated with improved survival outcomes in AKI, although they may also contribute to a heightened likelihood of complications, including acute renal failure and hyperkalemia [21]. Spironolactone, another RAAS system inhibitor, antagonizes aldosterone receptors but poses a danger of hyperkalemia [22]. However, it was reported that spironolactone treatment after 24 h of ischemic injury leading to AKI can improve renal inflammation and mitigate the progression from AKI to CKD [23].

Underlying molecular mechanisms of renal tubular injury in AKI

Activation of the complement system

The proximal tubules are the primary location of damage during renal ischemia-reperfusion injury (IRI), and complement activation on ischemic renal tubules significantly contributes to ischemic AKI [24]. Complement activation is mediated via three distinct pathways: the classical, lectin, and alternative pathways. Although these three pathways have different initiation mechanisms, they ultimately converge on C3 cleavage, leading to the activation of C3 and C5 and forming MAC, which induces cell activation or cleavage [15]. Data on complement mechanisms in AKI are mainly from animal models. The lectin complement pathway is activated in the renal tubules of mice with AKI in rhabdomyolysis, probably through an aberrant pattern of fucosyltransferase 2-dependent cytosolic fucosylation, recognized by the pattern-recognition molecule collectin-11 and in a C4-independent bypass manner [25]. Stimulation of TGF-β1 production in cultured mouse renal tubular cells after complement activation by C3a and C5a binding to C5a receptor and C3a receptor, and stimulation of proximal tubular epithelial cells by MAC leading to increased expression of type IV collagen mediate renal fibrosis resulting in the transition from AKI to CKD [26]. Furthermore, C3a mediates podocyte injury through TLR4/NF-κB-P65 signaling during IRI-AKI and post-injury fibrosis [27]. Ongoing complement-inhibiting drugs are currently used to treat a variety of kidney diseases causing AKI and exhibit promising efficacy (Table 2).

Table 2 Complement therapeutics for adult kidney diseases
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Mitochondrial impairment and autophagy pathway

Mitochondria serves as a principal source of cellular energy, with the proximal tubule being the primary locus of mitochondrial failure in AKI [28]. Mitochondrial damage seems to occur prior to the clinical manifestations of AKI following the onset of injury [29]. Electron microscopy revealed mitochondrial swelling, accompanied by minimal acute renal function impairment within 60 min of occluding a renal vessel [30]. Mitochondrial injury results in elevated reactive oxygen species (ROS), which subsequently exacerbates mitochondrial damage [31]. To reduce harm, the body activates mitochondrial autophagy to remove surplus or impaired mitochondria [32]. Augmented mitochondrial autophagy facilitates cell survival initially, while excessive activation of mitochondrial autophagy results in cell death and tissue injury [33]. Research indicates that the mitochondria-targeted antioxidant 10-(6’-plastoquinonyl) decylrhodamine 19 enhances renal blood flow and protects endothelial cells following renal ischemia-reperfusion [34].

Oxidative stress

The kidney utilizes substantial quantities of oxygen to provide energy for tubular reabsorption; consequently, renal tubules are particularly vulnerable to ischemia and hypoxic damage [35]. Ischemia and hypoxia in renal tubular cells elevate endogenous free radical production and disrupt mitochondrial oxidative phosphorylation, resulting in excessive ROS, while minimal ROS and free radicals can confer advantages to biological systems, their surplus induces oxidative stress, inflicting damage on various cellular structures, including membranes, proteins, lipids, and DNA [36, 37]. The oxidative stress processes of AKI primarily encompass ROS production, nitric oxide depletion, damage-associated molecular patterns (DAMPs) formation, toll-like receptors (TLRs) activation, autophagy, and microvascular dysfunction [38]. In IRI, DAMPs released from necrotic renal tubular cells activate TLRs on renal cells, initiating a cascade in inhibitor of NF-κB, resulting in its release and facilitating the nuclear translocation of NF-κB, within the nucleus, NF-κB drives the expression of inflammatory cytokines, oxidative bursts, and inflammatory responses, thereby exacerbating the injury process [39]. Prolonged exposure to oxidative stress stimuli in kidney tissue results in an initial inflammatory phase, subsequently leading to the excessive production of fibrous tissue, which compromises organ function and may result in CKD [40].

Antioxidant treatment shows promising results in AKI (Table 3). N-acetylcysteine (NAC) helps to mitigate contrast-induced AKI (CI-AKI), while Au NCs-NAC (ultra-small gold nanoclusters measuring 1–2 nm, capped with NAC) exhibit significantly enhanced therapeutic efficacy compared to NAC alone [41, 42]. Vitamin C sequesters reactive nitrogen species and ROS and replenishes endogenous glutathione levels, establishing its role as a vital antioxidant [43]. Preventive oral vitamin E in conjunction with a 0.9% saline infusion has been demonstrated to diminish the occurrence of CI-AKI in patients with CKD undergoing elective coronary angiography, as opposed to saline alone [44]. Lipoic acid decreases signs of oxidative stress and inflammatory response and has a preventative effect on the course of severe AKI [45]. Coenzyme Q10 possesses anti-peroxidative, anti-apoptotic, and anti-inflammatory properties and offers renoprotection after AKI [46]. Alongside topical treatments, the body possesses endogenous antioxidant systems that can alleviate damage from oxidative stress [47]. The clinical trials of antioxidants are currently being conducted vigorously and demonstrate favorable therapeutic outcomes (Table 4).

Table 3 Antioxidants for the treatment of AKI and the corresponding mechanisms
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Table 4 Ongoing antioxidants
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Inflammatory pathways

Damaged cells and immune cells release various cytokines (e.g., tumor necrosis factor (TNF), interleukin (IL)) and chemokines that attract neutrophils and macrophages from the bloodstream to the damaged site [48, 49]. Numerous studies indicate that pro-inflammatory cytokines and chemokines rely on NF-κB, binding to specific DNA regulatory elements, and triggering the expression of various inflammatory genes [50]. Tacrolimus can reduce the nuclear translocation of NF-κB, while glucocorticoids suppress the DNA-binding function of NF-κB [51]. In addition, glucocorticoids may be an effective therapeutic approach for septic AKI by mitigating mitochondrial damage, apoptosis, and anti-inflammatory [52].

Other inflammatory pathways are also involved in tubular injury in AKI. Research has demonstrated that NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome has an important role in CI-AKI models [53]. Remdesivir can suppress the activation of the NLRP3 inflammasome, therefore mitigating AKI [54]. TLR4 activates the NLRP3 inflammasome and the mitogen-activated protein kinases (MAPKs) phosphorylation inflammatory pathway, hence facilitating inflammatory reactions, inhibition of TLR4 confers a protective effect against sepsis-induced AKI in mice and represents a potential therapeutic approach for AKI [55, 56]. Furthermore, the thioredoxin-interacting protein facilitates the endoplasmic reticulum (ER) stress-mediated formation of the NLRP3 inflammasome complex and associates oxidative stress with the activation of the NLRP3 inflammasome, instigating mitochondria stress-induced apoptosis and promoting inflammatory cell death, thioredoxin-interacting protein may be a potential therapeutic target for AKI [57, 58].

The MAPK kinase signaling pathway activated by ROS from oxidative stress promotes the activation of activator protein-1, which regulates the modulation of pro-inflammatory cytokines and chemokines [59, 60]. Metformin mitigates inflammation, oxidative stress, and ER stress in renal tubular cells by activating 5’ Adenosine monophosphate-activated Protein Kinase in preclinical AKI models [61]. Pioglitazone improved IRI-AKI by attenuating oxidative stress and NLRP3 inflammasome activation [62]. The inflammasome-IL-1α/IL-1β-IL-1Receptor system is a pivotal component of renal inflammation and its systemic repercussions, with anti-inflammatory treatment utilizing IL-1 receptor antagonists being a viable option [63, 64]. Mast cells cause AKI through the production of TNF, and the application of TNF blockers (e.g., infliximab) protects renal function [65, 66]. Anti-inflammatory drugs for the treatment of AKI are summarized in Table 5. The ongoing clinical trials of anti-inflammatory drugs are summarized in Table 6.

Table 5 Anti-inflammatory drugs for the treatment of AKI and the corresponding mechanisms
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Table 6 Anti-inflammatory ongoing medicines
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Endoplasmic reticulum (ER) stress

The ER serves as the principal location for protein synthesis and processing, lipid metabolism, and signal transduction in the cell [67]. The accumulation of newly synthesized unfolded proteins due to ischemia, hypoxia, and oxidative stress induces ER stress, if ER stress is severe or prolonged, it ultimately results in cellular apoptosis, protein degradation, and translational attenuation [68]. Overall, In AKI, mild to moderate ER stress confers a protective effect on the kidneys, but severe ER stress worsens AKI [69]. The toxicity of clinically significant nephrotoxic agents, such as cisplatin and gentamicin, is markedly diminished in cells preconditioned with ER stress inducers [70]. However, TUG891 activates the G protein-coupled receptor 120, mitigating ER stress and apoptosis in cisplatin-induced AKI, thereby preserving kidney integrity [71]. Furthermore, ER stress is closely related to autophagy, which has a protective effect on ER stress-induced renal cell apoptosis, rapamycin enhances autophagy activity by inhibiting the mammalian target of rapamycin complex 1 to protect renal cells from ER stress-induced apoptosis [72].

Apoptosis and necrosis pathways

Proximal tubular cells exhibit significant metabolic activity and are susceptible to hypoxia and ischemia, rendering them a frequent locus for apoptosis and necrosis in AKI [35]. AKI encompasses several forms of renal cell death, including apoptosis, necrosis, pyroptosis, apoptosis-like necrosis, and ferroptosis [73]. Exposure of renal tubular cells to cisplatin results in tubular cell damage and mortality [74]. Cellular apoptosis and necrosis depend on trauma severity. Apoptosis involves intrinsic and extrinsic pathways and their interactions. Stress triggers the intrinsic pathway, releasing cytochrome c via Bcl-2-associated X protein/Bcl-2 antagonist killer 1-induced mitochondrial permeabilization, which activates caspase-9 and caspase-3, initiating apoptosis, in contrast, the extrinsic pathway involves Fas ligands binding death receptors, activating caspase-8, which triggers caspase-3 and cleaves BH3-interacting domain death agonist (Bid) into truncated Bid, which translocates to mitochondria, amplifying the intrinsic pathway and apoptotic cascade [8]. Selective reduction of pro-apoptotic genes, including Bax and Bak, reduces renal tubular cell apoptosis and offers protection against ischemia AKI [75]. Modulating specific apoptotic pathways may be advantageous for renal protection, the apoptosis of myofibroblast populations aids in renal recovery following IRI-AKI [76]. Recent discoveries indicate that ferroptosis plays a significant role in AKI. Ferroptosis is an iron-dependent form of cell death marked by the depletion of membrane lipid peroxidation products and plasma membrane polyunsaturated fatty acids, distinguishing it from apoptosis and necrosis [77]. Inhibition of necrosis and ferroptosis has demonstrated beneficial effects in many models of AKI [78].

Autophagy pathways

The induction of autophagy in proximal tubules during acute tubulointerstitial nephritis demonstrated that autophagy serves a nephroprotective function in AKI, nevertheless, excessive autophagy ultimately results in cellular demise [79]. Fibroblast growth factor 10 (FGF10) has been demonstrated to mitigate renal IRI-AKI by preventing excessive autophagy [80]. Autophagy may significantly modulate the inflammatory response in AKI, making the autophagy-inflammation axis a promising therapeutic target for AKI [81].

Underlying molecular mechanisms of renal vascular injury in AKI

Vascular endothelial damage

Under typical circumstances, endothelial cells perform activities including anticoagulation, anti-inflammation, vascular tone modulation, and release of vasoactive cytokines [82]. Damage to endothelial cells results in heightened secretion of the vasoconstrictor endothelin and diminished secretion of the vasodilator nitric oxide, causing sustained renal vasoconstriction, impaired renal perfusion, and aggravated renal injury [83]. Research indicates that the endothelin system is upregulated in AKI patients, this upregulation can promote the progression from AKI to CKD, and the use of selective antagonists of the endothelin-a receptor or non-dihydropyridine calcium channel blockers to block the endothelin system can protect the kidneys [84]. Meta-analyses indicate that the administration of inducible nitric oxide correlates with a diminished risk of AKI in individuals undergoing cardiac surgery, but it markedly elevates the risk of AKI in patients suffering from acute respiratory distress syndrome [85]. Furthermore, in the presence of ischemia and hypoxia, endothelial cells elevate the synthesis of ROS, and elevated levels of ROS inflict additional harm on endothelial cells [86].

Renal artery thrombosis and renal artery thromboembolism

Renal artery thromboembolism is a rare yet significant etiology of AKI, the formation of a thrombus in one or both arteries supplying blood to the kidneys results in diminished renal perfusion, potentially causing AKI [87]. Intact vascular endothelial cells possess anticoagulant properties; but upon activation due to endothelial injury, they facilitate renal artery thrombosis by initiating the blood coagulation cascade through the synthesis of procoagulant factors that enhance the generation and spread of thrombin [88]. Notably, renal artery thrombosis may arise as a secondary complication of coronavirus infection [89].

Vascular thinning

Vascular thinning denotes the diminishment of capillaries or a decrease in density, and the diminished density of renal microvessels may be a significant characteristic of the progression from AKI to CKD [90]. Contemporary therapies for vascular atrophy concentrate on protecting and rehabilitating the capillary network, numerous studies have suggested that the severity of AKI may be mitigated and the prognosis enhanced by facilitating neovascularization and protecting existing arteries [91].

Underling molecular mechanisms of renal interstitial injury in AKI

Immune cells-mediated damage

The renal interstitium houses the majority of the renal immune system, predominantly including dendritic cells, along with macrophages and fibroblasts [92]. Dendritic cells collect and deliver antigens to initiate adaptive immune responses [10]. Antigen-presenting cells, including dendritic cells and macrophages, convey antigens to naive T lymphocytes, triggering their activation and differentiation, CD4 + T helper cells are essential for coordinating immune responses by aiding B cells and activating cytotoxic CD8 + T cells, B lymphocytes mature into plasma cells, which generate antibodies that combat infections and facilitate their eradication [93]. B lymphocytes also secrete chemokines C-C motif-ligand 7 (CCL7), which recruit neutrophils and monocytes to the kidney during AKI [94]. Neutrophils contribute to inflammation by secreting cytokines, ROS, proteases, and other substances into renal tissue [95]. Macrophages are classified into type 1 and type 2, with M1 macrophages generating pro-inflammatory cytokines to promote inflammation, and M2 macrophages exhibit anti-inflammatory and pro-fibrotic properties [96]. Furthermore, interferon-γ, secreted by natural killer cells, activates M1 macrophages within renal tissue [97]. Various inflammatory cells release several inflammatory factors, infiltrate the renal interstitium, and aggravate renal injury [10].

Renal interstitial fibrosis

In AKI, renal interstitial cells generate significant quantities of inflammatory mediators, initiating sustained inflammatory responses that result in renal interstitial fibrosis and subsequently impair the recovery of kidney function [98]. Renal interstitial fibrosis is an irreversible phenomenon marked by the abnormal buildup of ECM, influenced by many cellular and molecular pathways [99]. During AKI, transitory Wnt-β-catenin signaling facilitates repair and regeneration, while persistent upregulation promotes renal fibrosis [100]. Snail 1-mediated partial transformation of epithelial cells into mesenchymal cells facilitates renal fibrosis in mice [101]. Additionally, AngII facilitates renal fibrosis by activating Janus kinases and MAPKs, promoting intracellular calcium influx via Ca2+ channels and enhancing the signaling pathways of TGF-β [102]. FGF23 is increased in individuals with AKI, and enhancement of FGF23 activates TGF-β and Wnt/β-catenin, promoting renal fibrosis and contributing to the transition from AKI to CKD [103, 104]. Research indicates that pirfenidone is a suitable choice for placebo-controlled trials in individuals with advanced CKD [105]. Subsequent investigations indicate that long-acting sustained-release pirfenidone did not enhance the clinical progression of septic AKI, however, it is safe and does not cause adverse effects [106].

The underlying molecular mechanisms in the four components of the kidney are summarized in Fig. 1. Inflammatory pathways are involved in the injuries in all four components. The reported mechanisms are not independent of each other, but rather interlinked with each other (Fig. 2).

Fig. 1
figure 1

Underlying molecular mechanisms of the pathogenesis of AKI (by Figdraw). Notes: Inflammatory pathways contribute to injuries in all four components of kidney. Abbreviations: RAAS: Renin-angiotensin-aldosterone system; ER: Endoplasmic reticulum; AKI: Acute kidney injury

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Fig. 2
figure 2

Interlinkages among mechanisms underlying AKI. Abbreviations: ROS: Reactive oxygen species; AngII: Angiotensin II; NF-κB: Nuclear factor-kappa B; IκB: Inhibitor of NF-Κb; TLR: Toll-like receptor; TXNIP: Thioredoxin-interacting protein; IL: Interleukin; C3a: Complement Components 3a; NLRP3: NOD-like receptor family, Pyrin domain containing 3; ER: Endoplasmic reticulum; AP-1: Activator protein-1; AKI: Acute kidney injury

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Conclusions

AKI is a critical concern in nephrology, inflicting considerable harm on both physical and mental health, while its elevated incidence and fatality rates place a tremendous strain on the healthcare system. The clinical diagnosis of AKI relies on changes in serum creatinine levels and urine output, lacking definitive methodologies. It is imperative to investigate the molecular pathways to create highly specific and readily observable diagnostic tools and to develop therapeutic agents targeting these mechanisms.

Data availability

No datasets were generated or analysed during the current study.

Abbreviations

AKI:

Acute kidney injury

AngII:

Angiotensin II

Bid:

BH3-interacting domain death agonist

CCL7:

Chemokines C-C motif-ligand 7

CI-AKI:

Mitigate contrast-induced AKI

CKD:

Chronic kidney disease

C3a:

Complement Components 3a

C5a:

Complement Components 5a

DAMPs:

Damage-associated molecular patterns

ECM:

Extracellular matrix

ER:

Endoplasmic reticulum

FGF10:

Fibroblast growth factor 10

GFR:

Decreased glomerular filtration rate

IL:

Interleukin

IRI:

Ischemia-reperfusion injury

MAC:

Membrane attack complex

MAPKs:

Mitogen-activated protein kinases

NAC:

N-acetylcysteine

NF-κB:

Transcription factor-kappa B

NLRP3:

NOD-like receptor family, pyrin domain containing 3

RAAS:

Renin-angiotensin-aldosterone system

ROS:

Reactive oxygen species

TGF-β:

Transforming growth factor-β

TLR4:

Toll-like receptor 4

TNF:

Tumor necrosis factor

References

  1. Sluman C, Gudka PM, McCormick K. Acute kidney injury: pre-renal, intra-renal and post-renal. Ren Med Clin Pharm. 2020;1:23–44.

  2. Susantitaphong P, Cruz DN, Cerda J, Abulfaraj M, Alqahtani F, Koulouridis I, et al. World incidence of AKI: A meta-analysis. Clin J Am Soc Nephrol. 2013;8(9):1482–93.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Darmon M, Clec’h C, Adrie C, Argaud L, Allaouchiche B, Azoulay E, et al. Acute respiratory distress syndrome and risk of AKI among critically ill patients. Clin J Am Soc Nephrol. 2014;9(8):1347–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Gambardella I, Gaudino M, Ronco C, Lau C, Ivascu N, Girardi LN. Congestive kidney failure in cardiac surgery: The relationship between central venous pressure and acute kidney injury. Interact Cardiovasc Thorac Surg. 2016;23(5):800–5.

    Article  PubMed  Google Scholar 

  5. See EJ, Jayasinghe K, Glassford N, Bailey M, Johnson DW, Polkinghorne KR, et al. Long-term risk of adverse outcomes after acute kidney injury: A systematic review and meta-analysis of cohort studies using consensus definitions of exposure. Kidney Int. 2019;95(1):160–72.

    Article  PubMed  Google Scholar 

  6. McCullough JW, Renner B, Thurman JM. The role of the complement system in acute kidney injury. Semin Nephrol. 2013;33(6):543–56.

    Article  CAS  PubMed  Google Scholar 

  7. Andrianova NV, Zorov DB, Plotnikov EY. Targeting inflammation and oxidative stress as a therapy for ischemic kidney injury. Biochem (Mosc). 2020;85(12):1591–602.

    Article  CAS  Google Scholar 

  8. Han SJ, Lee HT. Mechanisms and therapeutic targets of ischemic acute kidney injury. Kidney Res Clin Pract. 2019;38(4):427–40.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Anders HJ, Saxena R, Zhao MH, Parodis I, Salmon JE, Mohan C. Lupus nephritis. Nat Rev Dis Primers. 2020;6(1):7.

    Article  PubMed  Google Scholar 

  10. Tecklenborg J, Clayton D, Siebert S, Coley SM. The role of the immune system in kidney disease. Clin Exp Immunol. 2018;192(2):142–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Couser WG. Basic and translational concepts of immune-mediated glomerular diseases. J Am Soc Nephrol. 2012;23(3):381–99.

    Article  CAS  PubMed  Google Scholar 

  12. Novak J, Raskova Kafkova L, Suzuki H, Tomana M, Matousovic K, Brown R, et al. IgA1 immune complexes from pediatric patients with IgA nephropathy activate cultured human mesangial cells. Nephrol Dial Transpl. 2011;26(11):3451–7.

    Article  CAS  Google Scholar 

  13. Zwirner J, Felber E, Herzog V, Riethmüller G, Feucht HE. Classical pathway of complement activation in normal and diseased human glomeruli. Kidney Int. 1989;36(6):1069–77.

    Article  CAS  PubMed  Google Scholar 

  14. Anguiano L, Kain R, Anders HJ. The glomerular crescent: Triggers, evolution, resolution, and implications for therapy. Curr Opin Nephrol Hypertens. 2020;29(3):302–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Petr V, Thurman JM. The role of complement in kidney disease. Nat Rev Nephrol. 2023;19(12):771–87.

    Article  PubMed  Google Scholar 

  16. Ye B, Chen B, Guo C, Xiong N, Huang Y, Li M, et al. C5a-C5aR1 axis controls mitochondrial fission to promote podocyte injury in lupus nephritis. Mol Ther. 2024;32(5):1540–60.

    Article  CAS  PubMed  Google Scholar 

  17. Chou YH, Chu TS, Lin SL. Role of renin-angiotensin system in acute kidney injury-chronic kidney disease transition. Nephrol (Carlton). 2018;23(Suppl 4):121–5.

    Article  CAS  Google Scholar 

  18. Kagami S, Border WA, Miller DE, Noble NA. Angiotensin II stimulates extracellular matrix protein synthesis through induction of transforming growth factor-beta expression in rat glomerular mesangial cells. J Clin Invest. 1994;93(6):2431–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Wolf G, Bohlender J, Bondeva T, Roger T, Thaiss F, Wenzel UO. Angiotensin II upregulates toll-like receptor 4 on mesangial cells. J Am Soc Nephrol. 2006;17(6):1585–93.

    Article  CAS  PubMed  Google Scholar 

  20. Ma K, Gao W, Xu H, Liang W, Ma G. Role and mechanism of the Renin-Angiotensin-Aldosterone system in the onset and development of cardiorenal syndrome. J Renin Angiotensin Aldosterone Syst. 2022;2022:3239057.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Brar S, Ye F, James MT, Hemmelgarn B, Klarenbach S, Pannu N. Association of angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use with outcomes after acute kidney injury. JAMA Intern Med. 2018;178(12):1681–90.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Lindhardt JL, Nielsen PM, Hansen ESS, Qi H, Tougaard RS, Mariager C, et al. The hemodynamic and metabolic effects of spironolactone treatment in acute kidney injury assessed by hyperpolarized MRI. NMR Biomed. 2020;33(10):e4371.

    Article  CAS  PubMed  Google Scholar 

  23. Barrera-Chimal J, Rocha L, Amador-Martínez I, Pérez-Villalva R, González R, Cortés-González C, et al. Delayed spironolactone administration prevents the transition from acute kidney injury to chronic kidney disease through improving renal inflammation. Nephrol Dial Transpl. 2019;34(5):794–801.

    Article  CAS  Google Scholar 

  24. Thurman JM, Ljubanovic D, Edelstein CL, Gilkeson GS, Holers VM. Lack of a functional alternative complement pathway ameliorates ischemic acute renal failure in mice. J Immunol. 2003;170(3):1517–23.

    Article  CAS  PubMed  Google Scholar 

  25. Boudhabhay I, Poillerat V, Grunenwald A, Torset C, Leon J, Daugan MV, et al. Complement activation is a crucial driver of acute kidney injury in rhabdomyolysis. Kidney Int. 2021;99(3):581–97.

    Article  CAS  PubMed  Google Scholar 

  26. Franzin R, Stasi A, Fiorentino M, Stallone G, Cantaluppi V, Gesualdo L, et al. Inflammaging and complement system: A link between acute kidney injury and chronic graft damage. Front Immunol. 2020;11:734.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Chen Y, Lin L, Rao S, Tao X, Cui J, Wan J. Complement C3 mediates podocyte injury through TLR4/NFΚB-P65 signaling during ischemia-reperfusion acute kidney injury and post-injury fibrosis. Eur J Med Res. 2023;28(1):135.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Emma F, Montini G, Parikh SM, Salviati L. Mitochondrial dysfunction in inherited renal disease and acute kidney injury. Nat Rev Nephrol. 2016;12(5):267–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Ralto KM, Parikh SM. Mitochondria in acute kidney injury. Semin Nephrol. 2016;36(1):8–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Parekh DJ, Weinberg JM, Ercole B, Torkko KC, Hilton W, Bennett M, et al. Tolerance of the human kidney to isolated controlled ischemia. J Am Soc Nephrol. 2013;24(3):506–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Giorgi C, Marchi S, Simoes ICM, Ren Z, Morciano G, Perrone M, et al. Mitochondria and reactive oxygen species in aging and age-related diseases. Int Rev Cell Mol Biol. 2018;340:209–344.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Harper JW, Ordureau A, Heo JM. Building and decoding ubiquitin chains for mitophagy. Nat Rev Mol Cell Biol. 2018;19(2):93–108.

    Article  CAS  PubMed  Google Scholar 

  33. Aggarwal S, Mannam P, Zhang J. Differential regulation of autophagy and mitophagy in pulmonary diseases. Am J Physiol Lung Cell Mol Physiol. 2016;311(2):L433–52.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Jankauskas SS, Andrianova NV, Alieva IB, Prusov AN, Matsievsky DD, Zorova LD, et al. Dysfunction of kidney endothelium after ischemia/reperfusion and its prevention by mitochondria-targeted antioxidant. Biochem (Mosc). 2016;81(12):1538–48.

    Article  CAS  Google Scholar 

  35. Rahbar Saadat Y, Hosseiniyan Khatibi SM, Sani A, Zununi Vahed S, Ardalan M. Ischemic tubular injury: Oxygen-sensitive signals and metabolic reprogramming. Inflammopharmacology. 2023;31(4):1657–69.

    Article  CAS  PubMed  Google Scholar 

  36. Pizzino G, Irrera N, Cucinotta M, Pallio G, Mannino F, Arcoraci V, et al. Oxidative stress: Harms and benefits for human health. Oxid Med Cell Longev. 2017;2017:8416763.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Halliwell B. Biochemistry of oxidative stress. Biochem Soc Trans. 2007;35(Pt 5):1147–50.

    Article  CAS  PubMed  Google Scholar 

  38. Pavlakou P, Liakopoulos V, Eleftheriadis T, Mitsis M, Dounousi E. Oxidative stress and acute kidney injury in critical illness: Pathophysiologic mechanisms-biomarkers-interventions, and future perspectives. Oxid Med Cell Longev. 2017;2017:6193694.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Radi ZA. Immunopathogenesis of acute kidney injury. Toxicol Pathol. 2018;46(8):930–43.

    Article  CAS  PubMed  Google Scholar 

  40. Su H, Wan C, Song A, Qiu Y, Xiong W, Zhang C. Oxidative stress and renal fibrosis: Mechanisms and therapies. Adv Exp Med Biol. 2019;1165:585–604.

    Article  CAS  PubMed  Google Scholar 

  41. Tepel M, van der Giet M, Schwarzfeld C, Laufer U, Liermann D, Zidek W. Prevention of radiographic-contrast-agent-induced reductions in renal function by acetylcysteine. N Engl J Med. 2000;343(3):180–4.

    Article  CAS  PubMed  Google Scholar 

  42. Zhang DY, Tu T, Younis MR, Zhu KS, Liu H, Lei S, et al. Clinically translatable gold nanozymes with broad spectrum antioxidant and anti-inflammatory activity for alleviating acute kidney injury. Theranostics. 2021;11(20):9904–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Kaur KK, Allahbadia G, Singh M. An update in the utilization of N-acetyl cysteine & Vitamin C for tackling the oxidative stress in acute kidney injury secondary to robust sepsis-A systematic review. J Clin Nephrol. 2022;6(1):001–18.

    Article  Google Scholar 

  44. Rezaei Y, Khademvatani K, Rahimi B, Khoshfetrat M, Arjmand N, Seyyed-Mohammadzad MH. Short-term high-dose Vitamin E to prevent contrast medium-induced acute kidney injury in patients with chronic kidney disease undergoing elective coronary angiography: A randomized Placebo-Controlled trial. J Am Heart Assoc. 2016;5(3):e002919.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Ali RM, Khairy MA, Mansour DY. Effect of alpha-lipoic acid on acute lung injury and acute kidney injury in major postpartum hemorrhage. Ain Shams J Anesthesiology. 2016;9(2).

  46. Zhao S, Wu W, Liao J, Zhang X, Shen M, Li X, et al. Molecular mechanisms underlying the renal protective effects of coenzyme Q10 in acute kidney injury. Cell Mol Biol Lett. 2022;27(1):57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Day BJ. Antioxidant therapeutics: Pandora’s box. Free Radic Biol Med. 2014;66:58–64.

    Article  CAS  PubMed  Google Scholar 

  48. Ernandez T, Mayadas TN. The changing landscape of renal inflammation. Trends Mol Med. 2016;22(2):151–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Rabb H, Griffin MD, McKay DB, Swaminathan S, Pickkers P, Rosner MH, et al. Inflammation in AKI: Current understanding, key questions, and knowledge gaps. J Am Soc Nephrol. 2016;27(2):371–9.

    Article  CAS  PubMed  Google Scholar 

  50. Oeckinghaus A, Ghosh S. The NF-kappaB family of transcription factors and its regulation. Cold Spring Harb Perspect Biol. 2009;1(4):a000034.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Liu T, Zhang L, Joo D, Sun SC. NF-κB signaling in inflammation. Signal Transduct Target Ther. 2017;2:17023.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Choi HM, Jo SK, Kim SH, Lee JW, Cho E, Hyun YY, et al. Glucocorticoids attenuate septic acute kidney injury. Biochem Biophys Res Commun. 2013;435(4):678–84.

    Article  CAS  PubMed  Google Scholar 

  53. Shen J, Wang L, Jiang N, Mou S, Zhang M, Gu L, et al. NLRP3 inflammasome mediates contrast media-induced acute kidney injury by regulating cell apoptosis. Sci Rep. 2016;6:34682.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Yin L, Zhao H, Zhang H, Li Y, Dong Y, Ju H, et al. Remdesivir alleviates acute kidney injury by inhibiting the activation of NLRP3 inflammasome. Front Immunol. 2021;12:652446.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Yue L, Liu X, Wu C, Lai J, Wang J, Zhong H, et al. Toll-like receptor 4 promotes the inflammatory response in septic acute kidney injury by promoting p38 mitogen-activated protein kinase phosphorylation. J Bioenerg Biomembr. 2023;55(5):353–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Jha AK, Gairola S, Kundu S, Doye P, Syed AM, Ram C, et al. Toll-like receptor 4: An attractive therapeutic target for acute kidney injury. Life Sci. 2021;271:119155.

    Article  CAS  PubMed  Google Scholar 

  57. Zhou R, Tardivel A, Thorens B, Choi I, Tschopp J. Thioredoxin-interacting protein links oxidative stress to inflammasome activation. Nat Immunol. 2010;11(2):136–40.

    Article  CAS  PubMed  Google Scholar 

  58. Choi EH, Park SJ. TXNIP: A key protein in the cellular stress response pathway and a potential therapeutic target. Exp Mol Med. 2023;55(7):1348–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. McCubrey JA, Lahair MM, Franklin RA. Reactive oxygen species-induced activation of the MAP kinase signaling pathways. Antioxid Redox Signal. 2006;8(9–10):1775–89.

    Article  CAS  PubMed  Google Scholar 

  60. Kyriakis JM, Avruch J. Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation. Physiol Rev. 2001;81(2):807–69.

    Article  CAS  PubMed  Google Scholar 

  61. Song A, Zhang C, Meng X. Mechanism and application of metformin in kidney diseases: An update. Biomed Pharmacother. 2021;138:111454.

    Article  CAS  PubMed  Google Scholar 

  62. Ye Z, Zhang J, Xu Z, Li Z, Huang G, Tong B, et al. Pioglitazone ameliorates ischemia/reperfusion-induced acute kidney injury via oxidative stress attenuation and NLRP3 inflammasome. Hum Cell. 2024;37(4):959–71.

    Article  CAS  PubMed  Google Scholar 

  63. Anders HJ. Of inflammasomes and alarmins: IL-1β and IL-1α in kidney disease. J Am Soc Nephrol. 2016;27(9):2564–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Dinarello CA, Simon A, van der Meer JW. Treating inflammation by blocking interleukin-1 in a broad spectrum of diseases. Nat Rev Drug Discov. 2012;11(8):633–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Summers SA, Chan J, Gan PY, Dewage L, Nozaki Y, Steinmetz OM, et al. Mast cells mediate acute kidney injury through the production of TNF. J Am Soc Nephrol. 2011;22(12):2226–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Netrebenko AS, Gureev VV, Pokrovskii MV, Gureeva AV, Tsuverkalova YM, Rozhkov IS. Assessment of the nephroprotective properties of the erythropoietin mimetic peptide and infliximab in kidney ischemia-reperfusion injury in rats. Arch Razi Inst. 2021;76(4):995–1004.

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Almanza A, Carlesso A, Chintha C, Creedican S, Doultsinos D, Leuzzi B, et al. Endoplasmic reticulum stress signalling - from basic mechanisms to clinical applications. Febs J. 2019;286(2):241–78.

    Article  CAS  PubMed  Google Scholar 

  68. Inagi R. Endoplasmic reticulum stress in the kidney as a novel mediator of kidney injury. Nephron Exp Nephrol. 2009;112(1):e1–9.

    Article  PubMed  Google Scholar 

  69. Ni L, Yuan C, Wu X. Endoplasmic reticulum stress in diabetic nephrology: Regulation, pathological role, and therapeutic potential. Oxid Med Cell Longev. 2021;2021:7277966.

    Article  PubMed  PubMed Central  Google Scholar 

  70. Peyrou M, Cribb AE. Effect of endoplasmic reticulum stress preconditioning on cytotoxicity of clinically relevant nephrotoxins in renal cell lines. Toxicol Vitro. 2007;21(5):878–86.

    Article  CAS  Google Scholar 

  71. Huang Z, Guo F, Xia Z, Liang Y, Lei S, Tan Z, et al. Activation of GPR120 by TUG891 ameliorated cisplatin-induced acute kidney injury via repressing ER stress and apoptosis. Biomed Pharmacother. 2020;126:110056.

    Article  CAS  PubMed  Google Scholar 

  72. Dong G, Liu Y, Zhang L, Huang S, Ding HF, Dong Z. mTOR contributes to ER stress and associated apoptosis in renal tubular cells. Am J Physiol Ren Physiol. 2015;308(3):F267–74.

    Article  CAS  Google Scholar 

  73. Linkermann A. Nonapoptotic cell death in acute kidney injury and transplantation. Kidney Int. 2016;89(1):46–57.

    Article  PubMed  Google Scholar 

  74. Pabla N, Dong Z. Cisplatin nephrotoxicity: Mechanisms and renoprotective strategies. Kidney Int. 2008;73(9):994–1007.

    Article  CAS  PubMed  Google Scholar 

  75. Wei Q, Dong G, Chen JK, Ramesh G, Dong Z. Bax and bak have critical roles in ischemic acute kidney injury in global and proximal tubule-specific knockout mouse models. Kidney Int. 2013;84(1):138–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Chou YH, Pan SY, Shao YH, Shih HM, Wei SY, Lai CF, et al. Methylation in pericytes after acute injury promotes chronic kidney disease. J Clin Invest. 2020;130(9):4845–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Hu Z, Zhang H, Yang SK, Wu X, He D, Cao K, et al. Emerging role of ferroptosis in acute kidney injury. Oxid Med Cell Longev. 2019;2019:8010614.

    Article  PubMed  PubMed Central  Google Scholar 

  78. Sanz AB, Sanchez-Niño MD, Ramos AM, Ortiz A. Regulated cell death pathways in kidney disease. Nat Rev Nephrol. 2023;19(5):281–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Zeng Y, Li S, Wu J, Chen W, Sun H, Peng W, et al. Autophagy inhibitors promoted aristolochic acid I induced renal tubular epithelial cell apoptosis via mitochondrial pathway but alleviated nonapoptotic cell death in mouse acute aritolochic acid nephropathy model. Apoptosis. 2014;19(8):1215–24.

    Article  CAS  PubMed  Google Scholar 

  80. Tan X, Zhu H, Tao Q, Guo L, Jiang T, Xu L, et al. FGF10 protects against renal ischemia/reperfusion injury by regulating autophagy and inflammatory signaling. Front Genet. 2018;9:556.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Gong L, Pan Q, Yang N, Corrigendum: Autophagy and inflammation regulation in acute kidney injury. Front Physiol. 2021;11:639938.

    Article  PubMed  PubMed Central  Google Scholar 

  82. Krüger-Genge A, Blocki A, Franke RP, Jung F. Vascular endothelial cell biology: An update. Int J Mol Sci. 2019;20(18).

  83. Molema G, Zijlstra JG, van Meurs M, Kamps J. Renal microvascular endothelial cell responses in sepsis-induced acute kidney injury. Nat Rev Nephrol. 2022;18(2):95–112.

    Article  CAS  PubMed  Google Scholar 

  84. Czopek A, Moorhouse R, Gallacher PJ, Pugh D, Ivy JR, Farrah TE, et al. Endothelin blockade prevents the long-term cardiovascular and renal sequelae of acute kidney injury in mice. Sci Transl Med. 2022;14(675):eabf5074.

    Article  CAS  PubMed  Google Scholar 

  85. Wang J, Cong X, Miao M, Yang Y, Zhang J. Inhaled nitric oxide and acute kidney injury risk: A meta-analysis of randomized controlled trials. Ren Fail. 2021;43(1):281–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Alhayaza R, Haque E, Karbasiafshar C, Sellke FW, Abid MR. The relationship between reactive oxygen species and endothelial cell metabolism. Front Chem. 2020;8:592688.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Koivuviita N, Tertti R, Heiro M, Manner I, Metsärinne K. Thromboembolism as a cause of renal artery occlusion and acute kidney injury: The recovery of kidney function after two weeks. Case Rep Nephrol Urol. 2014;4(1):82–7.

    Article  PubMed  PubMed Central  Google Scholar 

  88. Yau JW, Teoh H, Verma S. Endothelial cell control of thrombosis. BMC Cardiovasc Disord. 2015;15:130.

    Article  PubMed  PubMed Central  Google Scholar 

  89. Acharya S, Anwar S, Siddiqui FS, Shabih S, Manchandani U, Dalezman S. Renal artery thrombosis in COVID-19. IDCases. 2020;22:e00968.

    Article  PubMed  PubMed Central  Google Scholar 

  90. de Bragança AC, Volpini RA, Mehrotra P, Andrade L, Basile DP. Vitamin D deficiency contributes to vascular damage in sustained ischemic acute kidney injury. Physiol Rep. 2016;4(13).

  91. Steegh F, Keijbeck AA, de Hoogt PA, Rademakers T, Houben A, Reesink KD, et al. Capillary rarefaction: A missing link in renal and cardiovascular disease? Angiogenesis. 2024;27(1):23–35.

    Article  PubMed  Google Scholar 

  92. Zeisberg M, Kalluri R. Physiology of the renal interstitium. Clin J Am Soc Nephrol. 2015;10(10):1831–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Foresto-Neto O, Menezes-Silva L, Leite JA, Andrade-Silva M, Câmara NOS. Immunology of kidney disease. Annu Rev Immunol. 2024;42(1):207–33.

    Article  CAS  PubMed  Google Scholar 

  94. Inaba A, Tuong ZK, Riding AM, Mathews RJ, Martin JL, Saeb-Parsy K, et al. B Lymphocyte-Derived CCL7 augments neutrophil and monocyte recruitment, exacerbating acute kidney injury. J Immunol. 2020;205(5):1376–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Gupta S, Kaplan MJ. The role of neutrophils and NETosis in autoimmune and renal diseases. Nat Rev Nephrol. 2016;12(7):402–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Rogers NM, Ferenbach DA, Isenberg JS, Thomson AW, Hughes J. Dendritic cells and macrophages in the kidney: A spectrum of good and evil. Nat Rev Nephrol. 2014;10(11):625–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Law BMP, Wilkinson R, Wang X, Kildey K, Lindner M, Rist MJ, et al. Interferon-γ production by tubulointerstitial human CD56(bright) natural killer cells contributes to renal fibrosis and chronic kidney disease progression. Kidney Int. 2017;92(1):79–88.

    Article  CAS  PubMed  Google Scholar 

  98. Neumann K, Tiegs G. Immune regulation in renal inflammation. Cell Tissue Res. 2021;385(2):305–22.

    Article  PubMed  PubMed Central  Google Scholar 

  99. Liang L, Mi Y, Zhou S, Yang A, Wei C, Dai E. Advances in the study of key cells and signaling pathways in renal fibrosis and the interventional role of Chinese medicines. Front Pharmacol. 2024;15:1403227.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Schunk SJ, Floege J, Fliser D, Speer T. WNT-β-catenin signalling - a versatile player in kidney injury and repair. Nat Rev Nephrol. 2021;17(3):172–84.

    Article  CAS  PubMed  Google Scholar 

  101. Grande Rodríguez M, López Blau C, Sánchez Laorden B, Frutos CAd, Boutet A, Grant Rowe R, et al. Snail1 factor behaves as a therapeutic target in renal fibrosis. 2015.

  102. AlQudah M, Hale TM, Czubryt MP. Targeting the renin-angiotensin-aldosterone system in fibrosis. Matrix Biol. 2020;91–92:92–108.

    Article  PubMed  PubMed Central  Google Scholar 

  103. Christov M, Waikar SS, Pereira RC, Havasi A, Leaf DE, Goltzman D, et al. Plasma FGF23 levels increase rapidly after acute kidney injury. Kidney Int. 2013;84(4):776–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Lu Y, Xu S, Tang R, Han C, Zheng C. A potential link between fibroblast growth factor-23 and the progression of AKI to CKD. BMC Nephrol. 2023;24(1):87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Cho ME, Smith DC, Branton MH, Penzak SR, Kopp JB. Pirfenidone slows renal function decline in patients with focal segmental glomerulosclerosis. Clin J Am Soc Nephrol. 2007;2(5):906–13.

    Article  CAS  PubMed  Google Scholar 

  106. Chávez-Iñiguez JS, Poo JL, Ibarra-Estrada M, García-Benavides L, Navarro-Blackaller G, Cervantes-Sánchez C, et al. Effect of Prolonged-Release Pirfenidone on renal function in septic acute kidney injury patients: A Double-Blind Placebo-Controlled clinical trial. Int J Nephrol. 2021;2021:8833278.

    Article  PubMed  PubMed Central  Google Scholar 

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  1. Department of Nephrology, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, China

    Jiajia He & Yanqin Chen

  2. Department of Nephrology and Institute of Nephrology, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Sichuan Clinical Research Centre for Kidney Diseases, Chengdu, 610072, China

    Yi Li & Yunlin Feng

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JH did literature research, extracted the data, and drafted the manuscript. YF designed the research and reviewed the manuscript. All authors reviewed the manuscript. All authors read and approved the final manuscript.

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Correspondence to Yunlin Feng.

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He, J., Chen, Y., Li, Y. et al. Molecular mechanisms and therapeutic interventions in acute kidney injury: a literature review. BMC Nephrol 26, 144 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12882-025-04077-4

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