Although renal fibrosis is predominantly driven by the accumulated inflammatory cells that secrete proinflammatory factors within the kidney, the key mechanisms underlying macrophage clearance from the kidney are not well understood. The interaction of hyaluronan with lymphatic endothelial hyaluronan receptor 1 (LYVE1) constitutes a critical initial step in macrophage adhesion and removal by lymphatic vessels. This study investigates alterations in LYVE1 during kidney disease and elucidates its role in macrophage trafficking. Three renal fibrosis models demonstrated a reduction in full-length LYVE1 and an increase in the soluble LYVE1 fragment. Immunostaining of fibrotic kidneys showed significantly reduced expression of soluble LYVE1 compared with the intracellular fragment (Cyto-LYVE1), demonstrating ectodomain shedding of LYVE1 in vivo and in vitro. Functionally, human lymphatic endothelial cells exposed to TGF-β1 exhibited a significant decrease in macrophage adhesion and transendothelial migration compared with controls. Mechanistic analyses identified increased matrix metalloproteinase 9 (MMP9) in renal injury as a key upstream regulator of LYVE1 shedding. MMP9 inhibitors reduced LYVE1 shedding, enhanced macrophage adhesion and trafficking, and mitigated macrophage accumulation and disease progression. In conclusion, MMP9-induced LYVE1 shedding is linked to progressive kidney fibrosis and macrophage accumulation. LYVE1 shedding inhibitors offer potential as therapeutic agents for mitigating immune overload and kidney fibrosis.

The objective of this completed, randomized, open-label trial across 11 hemodialysis centers in Shanghai, China, was to evaluate whether hemoadsorption combined with hemodialysis (HAHD) reduces mortality compared to hemodialysis (HD) alone in end-stage kidney disease patients (maintenance HD ≥ 3 months, Kt/V ≥ 1.2). We randomized 1362 patients 1:1 to receive HAHD (n = 683) or HD alone (n = 679; mainly low-flux HD plus intermittent HDF). All 1362 randomized patients were analyzed. The primary outcome was all-cause mortality, while secondary outcomes included cardiovascular mortality and major cardiovascular events. Over a median follow-up of 39.5 months, all-cause mortality occurred in 117 (17.1%) of HAHD patients compared to 144 (21.2%) of HD patients (hazard ratio [HR]: 0.778, 95% confidence interval [CI]: 0.609-0.994; P = 0.045). HAHD also significantly reduced cardiovascular mortality (HR: 0.659, 95% CI: 0.481-0.901; P = 0.009) and major cardiovascular events (HR: 0.772, 95% CI: 0.621-0.959; P = 0.019). Important adverse events, primarily infections and abnormal blood pressure, were comparable between the two groups. Adding hemoadsorption significantly reduced all-cause mortality, cardiovascular mortality, and major cardiovascular events compared to HD alone (mainly low-flux HD plus intermittent HDF). Trial Registration: ClinicalTrials.gov NCT03227770.

In recent years, rates of maternal obesity before conception have continued to rise globally. Maternal obesity in early pregnancy may alter intrauterine immune mechanisms, impact fetal metabolic programming, and increase the risk of later-life obesity. This study aimed to review the literature on changes in immune parameters and weight-related outcomes in offspring reported in human and animal studies of maternal obesity. A systematized literature search was conducted using PubMed and Web of Science for relevant human and animal studies published between 2010 and 2025. Study screening was facilitated using Rayyan. The risk of bias was assessed using SYRCLE for animal studies and LEGEND for human studies. Fifteen studies reporting birth weight outcomes showed conflicting findings, with three reporting higher birth weight, three reporting lower birth weight in offspring of mothers with versus without obesity, eight reporting no significant association, and one study did not report a p-value. These discrepancies may reflect heterogeneity in study models (e.g., Sprague–Dawley rats, C57BL/6J mice, and rhesus macaques), dietary compositions (e.g., cafeteria diet, Western-style diet, and high-fat diet), and species (animal versus human studies). In animal studies, gene expression analyses across different species and sample sources consistently showed upregulation of TLR2, ARG1, VEGF, TNF, and NF-κB, but variable trends for TNF-α, IL-10, IL-6, TLR4, TRAF6, STAT3, and MCP-1(CCL2). In human studies, placental gene expression of IL-1β, MCP-1 (CCL2), CXCR2, STAT3, P38-MAPK, and IL-8 varied across studies, while blood levels of IL-6, CRP, microRNAs, and antibodies also showed inconsistency. Placental macrophage and neutrophil counts were increased in humans, whereas animal studies consistently reported increased placental macrophage counts. Maternal pre-pregnancy or first trimester obesity showed inconsistent effects on offspring birth weight; however, it is associated with alterations in multiple immune parameters and may induce placental inflammation via the macrophage TLR2–NF-κB–p38 signaling pathway.

Long interspersed nuclear element 1 (LINE-1 or L1) retrotransposons pose a significant threat to somatic genomic integrity and are a source of sterile inflammation. Consequently, L1 activity is stringently controlled by multiple regulatory layers to ensure silencing, while its transcriptional derepression is linked to aging and age-related diseases. Recent studies have revealed complex interrelationships between L1 and cGAS, but whether cGAS regulates L1 transcription and its biological significance remains unclear. Here, we demonstrate that human cGAS activates L1 transcription by upregulating the transcriptional regulators CTCF and RUNX3. This cGAS-mediated promotion of L1 transcription is absent in mice due to functional divergence in CTCF and RUNX3. Furthermore, cGAS-mediated elevation of L1 mRNA promotes cellular senescence via MAVS, a key RNA-sensing pathway component. Together, our findings reveal a novel role of cGAS in activating L1 transcription and define a cGAS-L1-MAVS senescence pathway, thereby bridging the noncanonical function of cGAS and the RNA-sensing signaling.

Lysyl oxidase (LOX) is a copper-dependent monoamine oxidase whose primary function is the covalent cross-linking of collagen and elastin in the extracellular matrix (ECM). However, the regulation of LOX activity in renal fibrosis is not well understood. Here, our study showed that (a) LOX expression and ECM cross-linking were markedly increased in fibrotic kidneys. Reduction of copper levels in the Golgi apparatus by treatment with the copper chelator tetrathiomolybdate or by specific knockdown of copper transporter 1 (CTR1) decreased LOX activity and ameliorated renal fibrosis. (b) Overexpression of ATP7A caused an elevation of copper ions within the Golgi apparatus, resulting in increased LOX activity and enhanced ECM crosslinking, thereby promoting the progression of renal fibrosis. Knockdown of ATP7A showed the opposite result. (c) FBLN4 was essential for the ATP7A-mediated transfer of copper to LOX and formed a ternary complex of ATP7A-FBLN4-LOX. Our research revealed that high ATP7A expression induced copper overload in the Golgi apparatuses. FBLN4 then assisted ATP7A in transporting this excess copper to LOX, resulting in LOX overactivation. This, in turn, catalyzed the cross-linking of ECM components, thereby accelerating renal fibrosis.

Introduction China accounts for approximately one quarter of the global elderly population. This review provides a comprehensive overview of the development of Chinese geriatric medicine (CG) from its inception to the present, within the context of population ageing and the “Healthy China” initiative. Methods The review examines the current status, identifies key challenges, and considers potential future directions of CG. Results Efforts in CG encompass multiple strategic areas, including the creation of age-friendly environments, formulation of policy guidance, establishment of clinical and service standards, advancement of scientific research, professional workforce training, implementation of smart health services, integration of traditional Chinese and western medicine, delivery of personalized and continuous integrated care, and fostering international collaboration. Conclusion This uniquely Chinese model of CG development offers a valuable framework that may inform and guide the evolution of geriatric medicine globally, particularly in other developing countries.

Chronic kidney disease (CKD) affect about 10% of adults worldwide, with dyslipidemia being a common feature. Abnormalities in renal lipid metabolism have been strongly implicated in CKD progression; however, the mechanisms by which CKD leads to lipid metabolism disturbances remain underexplored. Here we show that following the accumulation of uremic toxins, the synthesis and deposition of lipids, along with the uremic toxin receptor aryl hydrocarbon receptor (AhR), are upregulated in the kidneys. Tubule-specific AhR knockout in male mice alleviates uremic toxin-induced increases in renal fatty acid (FA) synthesis, lipid accumulation and fibrosis. Immunoprecipitation‒mass spectrometry identifies nuclear receptor subfamily 1 group D member 1 (NR1D1) as an AhR-interacting protein. Co-immunoprecipitation confirms that AhR interacts with NR1D1 and promotes its ubiquitin-mediated degradation. As NR1D1 is an FA synthesis suppressor, its reduction relieves the transcriptional repressing effects on sterol regulatory element-binding protein 1 (SREBP1), thereby enhancing SREBP1/fatty acid synthase (FASN) pathway activity and FA synthesis. In summary, by acting on AhR, the accumulation of uremic toxins may accelerate renal fibrosis via the SREBP1/FASN pathway-mediated increase in FA synthesis.

Epidermal growth factor receptor (EGFR) signalling plays a crucial role in renal fibrosis. We previously demonstrated that EGFR mimotope vaccination could alleviate renal fibrosis by restoring major histocompatibility complex class IB (MHC-IB) expression in renal tubular epithelial cells and promoting MHC-IB-enriched exosome release. Intriguingly, the mechanism by which the EGFR mimotope affects MHC-IB remains unknown. In this study, we demonstrated that administering purified EGFR mimotope-induced antibodies (EM-pAb) can effectively upregulate ribosomal protein ligand (RPL)-6, poly (rC) binding protein 2 (PCBP2), and MHC-IB in tubular epithelial cells. Mechanistically, the EM-pAb promoted EGFR/ribosomal protein ligand 6 (RPL6)/poly (rC) binding protein 2 (PCBP2) functional ternary complex formation, re-established the binding capability of PCBP2 to MHC-IB β-chain, and further regulated the NK cell population. RPL6 was confirmed as the key orchestrator of the ternary complex formation. Rpl6CKI mice further revealed the protective role of RPL6 in the animal model of renal fibrosis. RPL6 and kidney function showed a significant correlation in patients with chronic kidney disease. Overall, our findings uncover the signalling pathway by which EGFR modulates MHC-IB and validate the regulatory role of EM-pAb in this signalling pathway, indicating the therapeutic potential of RPL6 in chronic kidney disease.

Superoxide dismutase 1 (SOD1), a copper-dependent antioxidant, is essential for redox homeostasis, and its decline drives renal senescence and fibrosis. However, the mechanisms linking profibrotic signaling to SOD1 inhibition remain unclear. Here, we identified a pathological copper-COMMD1-SOD1 axis in which intracellular copper overload paradoxically suppressed SOD1 activity. In kidney tissues from chronic kidney disease (CKD) patients and complementary in vivo and in vitro fibrotic models, we consistently observed a reduction in SOD1 activity accompanied by elevated intracellular copper levels. Lowering intracellular copper levels restored SOD1 activity, suppressed reactive oxygen species (ROS) accumulation, and alleviated cell senescence and fibrosis. Mechanistically, pathological copper overload impaired SOD1 homodimerization, the essential final step in its activation. We identified copper metabolism MURR1 domain containing 1 (COMMD1) as a key copper-sensitive mediator of this process. Copper overload acted upstream, simultaneously upregulating COMMD1 expression and enhancing its binding affinity to SOD1. This enhanced COMMD1-SOD1 interaction directly disrupted SOD1 homodimer assembly and enzymatic function. Collectively, these findings redefined the regulatory role of copper in SOD1 activity and uncovered a previously unrecognized mechanism by which pathological copper overload paradoxically suppressed SOD1 activity via COMMD1-dependent disruption of SOD1 homodimerization, providing new insight into the pathophysiology of copper dyshomeostasis-associated diseases.

Introduction: Individuals with end-stage kidney disease frequently grapple with uncontrolled hypertension, which elevates their risk for cardiovascular complications. Methods: This randomized, controlled, multicenter study, conducted across 10 hospitals, aimed to compare the effectiveness and safety of sacubitril-valsartan versus irbesartan in managing hypertension among dialysis patients. The primary efficacy variable of the present study was the reduction in office blood pressure (BP) after 12 months of treatment. Participants were randomly allocated to receive either sacubitril-valsartan (angiotensin receptor-neprilysin inhibitor [ARNI]) or irbesartan (angiotensin receptor blocker [ARB]) treatment over a 12-month period. We gauged treatment efficacy through office and 24-h ambulatory BP readings, as well as serum concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP). Safety outcomes were also evaluated. Results: Baseline office BP averaged 150/82 mm Hg and median NT-proBNP was 6,336 pg/mL. In the intention-to-treat analysis, office systolic BP reduction was significantly greater in the ARNI than ARB group (−10.4 vs. −4.6 mm Hg, p = 0.003) after adjustment for baseline BP. In hemodialysis (HD) patients, the mean systolic/diastolic BP reduction was also greater in the ARNI than ARB group (−15.9/2.4 vs. −6.6/1.1 mm Hg, p < 0.05). While for peritoneal dialysis (PD) patients, there were no significant between-group differences (p = 0.087). Per-protocol analyses in 215 patients on office BP and 137 patients on 24-h BP produced similar results. During the study period, there was no between-group difference in the overall incidence of fatal and nonfatal events and hyperkalemia. Conclusion: In dialysis patients with hypertension, especially those undergoing HD, ARNI demonstrated superior effectiveness in reducing BP compared to ARB. The safety profiles of both treatments were comparable and acceptable.

BACKGROUND:Renal fibrosis, the terminal pathological pathway of chronic kidney disease (CKD), lacks reliable noninvasive biomarkers for clinical assessment. Current diagnostic reliance on renal biopsy-despite its gold-standard status-poses risks of bleeding and sampling errors, necessitating alternatives. Long non-coding RNA growth arrest-specific 5 (GAS5) regulates fibrogenic pathways, but its utility as a liquid biopsy marker remains unexplored. METHOD:This prospective cross-sectional study quantified GAS5 levels in paired plasma and urine samples from 198 CKD patients (stratified by renal fibrosis scoring: mild: <25%, moderate: 25-50%, severe: ≥50% fibrotic area) and 20 healthy controls. Multivariate regression models adjusted for cardiorenal confounders (hypertension, blood pressure, and so on) evaluated GAS5's association with fibrosis. RESULTS:Plasma GAS5 levels increased with renal fibrosis severity, whereas urinary GAS5 exhibited progressive suppression. After adjusting for factors such as hypertension history, systolic and diastolic blood pressure, blood urea nitrogen, creatinine, eGFR, and uric acid, use of ACEI/ARB, multivariate analysis showed significant associations between urinary GAS5 level and renal fibrosis. ROC analysis revealed urinary GAS5's superior diagnostic accuracy compared with eGFR and TGF-β1. AUCs of urinary GAS5 were even higher in moderate and severe renal fibrosis group. CONCLUSIONS:While plasma GAS5 upregulation and urinary GAS5 suppression reflect inverse expression patterns in renal fibrosis, urinary GAS5 emerges as the dominant noninvasive biomarker due to its superior diagnostic performance (AUC = 0.868) and clinical accessibility.

Renal epithelial cell senescence and kidney aging have become the focus of scientific investigation. However, how epigenetic regulation in these processes remains elusive. Enhancer of zeste homolog 2 (EZH2), a histone methyltransferase, regulates trimethylation of histone H3 at lysine 27 (H3K27me3) and plays an important role in renal pathophysiology. In this study, we show that the expression of EZH2 is decreased in naturally aged and irradiation (IR)-induced mouse kidneys, as well as in IR-induced human renal cortical tubular epithelial (RCTE) cells through proteasome-mediated degradation. Inhibition of EZH2 with its specific inhibitor 3-DZNeP promotes tubular cell senescence and kidney aging characterized by an increase in the expression of senescence markers, including p16 and p21, in mouse kidneys and in IR-induced RCTE cells. We show that EZH2 represses the transcription of p16 through trimethylation of H3K27me3, which directly binds to the promoter of p16. EZH2 represses the transcription of p21 through directly binding to the promoter of p21, and this process is involved in its interaction with p53 and its phosphorylation by ataxia-telangiectasia mutated (ATM), a critical protein involved in the cellular response to DNA damage. Inhibition of ATM with its inhibitor decreased the phosphorylation of EZH2 and the binding of EZH2 to the promoter of p21 in IR-treated RCTE cells in a p53-dependent manner. This study suggests that EZH2 plays a critical role in preventing kidney aging and DNA-damage-induced renal tubular cellular senescence, in which senescence and kidney aging also result in the destabilization of EZH2, forming a negative feedback loop.

BACKGROUNDS:This study aimed to perform risk stratification for sepsis-induced cardiorenal syndrome (CRS) and develop an early prediction model enabling the timely identification of high-risk patients within the first 24 h of admission. METHODS:This study retrospectively extracted septic patient data from the Shanghai Tongji Hospital between 2015 and 2020, with CRS occurrence set as the outcome measure. The Least Absolute Shrinkage and Selection Operator regression followed by multivariable logistic regression was applied to screen the candidate variables and develop the prediction model. Model performance was assessed through discrimination, calibration and decision curve analysis. Model interpretability was enhanced using SHapley Additive exPlanations values and visualized via a nomogram. RESULTS:A total of 1,580 patients diagnosed with sepsis at admission in Shanghai Tongji Hospital were enrolled. Sequential Organ Failure Assessment score, blood urea nitrogen, myoglobin, serum creatinine and diuretics were the five most influential predictors for early cardio-renal dysfunction. The five-variable combined model presented strong discrimination with the area under the curve of 0.828 (95%CI: 0.801-0.854) and 0.862 (95%CI: 0.823-0.901), and showed fine calibration with the Brier score of 0.169 and 0.148 in the training and validation groups, respectively. Myoglobin consistently showed superior performance to cardiac troponin I (cTnI) in predicting CRS. CONCLUSIONS:Our findings suggest that elevated serum myoglobin may serve as a useful early biomarker for identifying patients at risk of sepsis-induced CRS, outperforming cTnI in this cohort. The proposed model could support early risk stratification and inform timely clinical decision-making in critical care settings.

DNA repair, an evolutionarily conserved mechanism essential for restoring genetic homeostasis, has been implicated in aging and longevity by multiple lines of evidence. However, due to the challenges in obtaining human research materials, studies on the interplay between DNA repair and aging rely primarily on laboratory animal models, whose regulatory mechanisms may not fully mirror those in humans. Strikingly, the rate of aging varies by nearly an order of magnitude across humans, ranging from individuals with progeroid syndromes (lifespans under a decade) to the longest-lived recorded person (122 years). This extreme diversity provides a unique framework for comparative analysis of lifespan regulation in humans. By integrating advances in DNA repair studies across humans with divergent aging trajectories, this review provides novel insights into the molecular basis of DNA repair and lifespan, highlighting promising targeted therapies to promote longevity through precise modulation of DNA repair pathways.

Renal fibrosis is a characteristic of the progression of various chronic kidney diseases (CKD) to end-stage renal disease (ESRD). The renin-angiotensin system (RAS) is key to renal pathology. A better understanding of its regulatory mechanisms at the molecular level may lead to solutions for clinical CKD. Interestingly, our cohort study observed a positive correlation between epithelial dipeptidyl peptidase-IV (DPP4) levels and clinical CKD progression. Consistently, DPP4 was significantly increased in the unilateral ureteral obstruction (UUO) injured kidney in vivo and human epithelial kidney HK-2 cells under Ang II stimulation in vitro. Unexpectedly, kidney-specific deletion of DPP4 effectively ameliorated UUO and ischemia/reperfusion (I/R)-driven renal fibrosis in vivo. Mechanistically, we reveal that DPP4 serves as a novel inhibitor of the Ang(1-7)/MasR axis and an inducer of the AT1R axis by directly binding to ACE2 at the protein level. More importantly, targeting DPP4 with pharmaceutical inhibitor linagliptin effectively restored anti-fibrotic pathway of RAS, thereby blocking the CKD progression of I/R-injured kidney in vivo. Therefore, epithelial DPP4 may represent a precise therapeutic target to enhance the anti-fibrotic activity of RAS for CKD treatment in the clinic.

Introduction:IgA nephropathy (IgAN), the most common primary glomerulonephritis, often presents with advanced renal failure and end-stage renal disease at diagnosis. Till now, there remains a lack of reliable biomarkers for effectively assessing the progression risk of IgAN. Here, we propose lysyl oxidase (LOX), a marker of collagen cross-linking, as a potential biomarker for assessing fibrosis in IgAN. Method:After evaluating the fibrosis degree by Masson staining, measuring LOX levels in serum and kidney tissues, and collecting clinical information, we analyzed the association between LOX and renal fibrosis. Logistic regression analysis was employed to identify significant variables, which were incorporated into a nomogram and machine-learning model. Results:A total of 128 IgAN patients were enrolled in the study, of which 89 were included in the training cohort and 39 patients in the validation cohort. Serum LOX levels correlated with the area of renal fibrosis (r = 0.673, p < 0.001). ROC analysis of LOX showed an AUC of 0.793 and 0.785 with optimal cutoff values of 297.59 pg/mL and 395.02 pg/mL for the prediction of mild and moderate-to-severe renal fibrosis, respectively. The diagnostic nomogram model for predicting renal function decline within 3 years incorporated traditional clinical determinants along with the Oxford MEST histological score (model 1), achieving an AUC of 0.740 (95% CI: 0.565-0.914, p < 0.05). In contrast, a model (model 2) that combined traditional clinical determinants with LOX instead of the Oxford MEST histological score demonstrated improved predictive performance, yielding an AUC of 0.806 (95% CI: 0.655-0.956, p < 0.01). Conclusions:Serum LOX has the potential to predict renal fibrosis in IgAN. When combined with traditional clinical indicators, it may enhance the prediction of IgAN prognosis.

Ferredoxin 1 (FDX1) is a small iron-sulfur (Fe-S) cluster protein localized to the mitochondria. It functions as an electron carrier in diverse metabolic pathways and is critically involved in regulating protein lipoylation Accumulating evidence indicates that FDX1 expression is frequently dysregulated across various cancer types. Its expression is significantly associated with cancer progression, prognosis, and tumor immune responses, suggesting its potential as a biomarker for cancer diagnosis, prognostic evaluation, and immunotherapy response prediction. Transcription factors, epigenetic modifications, and non-coding RNAs (ncRNAs) contribute to the aberrant expression of FDX1 in cancer cells. Mechanistic studies reveal that FDX1 protein influences cancer progression by modulating oncogenic signaling pathways, metabolic reprogramming, and tumor immunity; Notably, FDX1 serves as a central mediator of cuproptosis - a copper-dependent form of programmed cell death - highlighting its potential tumor-suppressive function. Therefore, FDX1 may exert dual roles in cancer by either promoting or inhibiting disease progression. Recently, several agents targeting FDX1 have exhibited promising therapeutic efficacy both in vitro and in vivo across diverse cancer models. In this review, we summarize the regulatory mechanisms governing FDX1 expression and its functional roles in cancer progression. We also highlight its potential as a therapeutic target in cancer therapy.

Efficient DNA repair might make possible the longevity of naked mole-rats. However, whether they have distinctive mechanisms to optimize functions of DNA repair suppressors is unclear. We find that naked mole-rat cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS) lacks the suppressive function of human or mouse homologs in homologous recombination repair through the alteration of four amino acids during evolution. The changes enable cGAS to retain chromatin longer upon DNA damage by weakening TRIM41-mediated ubiquitination and interaction with the segregase P97. Prolonged chromatin binding of cGAS enhanced the interaction between repair factors FANCI and RAD50 to facilitate RAD50 recruitment to damage sites, thereby potentiating homologous recombination repair. Moreover, the four amino acids mediate the function of cGAS in antagonizing cellular and tissue aging and extending life span. Manipulating cGAS might therefore constitute a mechanism for life-span extension.

Lactylation, a novel post-translational modification, has been implicated in various pathophysiological processes; however, its role in sepsis-associated acute kidney injury (SA-AKI) remains unclear. This study aimed to investigate the expression patterns and potential functional roles of lactylation-related genes (LRGs) in SA-AKI using transcriptomic data from the GSE232404 dataset. A total of 118 differentially expressed LRGs were identified, enriched in pathways related to RNA splicing, histone deacetylation, and carbon metabolism pathways. Immune infiltration analysis revealed significant alterations in macrophages M0, neutrophils, and T cell subtypes. Consensus clustering-based molecular subtyping stratified SA-AKI samples into two distinct clusters, each characterized by unique immune landscapes and enrichment in cytokine signaling pathways. Weighted gene co-expression network analysis (WGCNA) identified the darkseagreen3 module as highly correlated with these subtypes. Subsequent machine learning analyses, incorporating Lasso regression and random forest algorithms, identified PECR and TP53I3 as key LRGs. Transcription factor enrichment analysis further suggested motif cisbp__M1413 as a potential upstream regulator. Single-cell RNA sequencing (scRNA-seq) analysis revealed PECR and TP53I3 were predominant expression in proximal tubule and Loop of Henle cells, with significant correlations to lactylation-related pathways. This comprehensive analysis finds the potential roles of LRGs in SA-AKI pathogenesis, particularly their association with immune regulation and cell-type specificity. The identified of PECR and TP53I3 provides new insights into the molecular mechanisms of SA-AKI and may inform the development of targeted therapeutic strategies.