ObjectiveMembranous nephropathy （MN） is a leading cause of nephrotic syndrome in adults. This study aimed to evaluate the clinical efficacy of rituximab （RTX） in patients with idiopathic membranous nephropathy （IMN） at high risk of progression.MethodsWe retrospectively analyzed 70 consecutive， treatment‑naïve IMN patients who received RTX as initial therapy in the Department of Nephrology， the Second Hospital， Lanzhou University， between January and December 2023. Inclusion criteria were high anti‑phospholipase A2 receptor （anti‑PLA2R） antibody titers， severe proteinuria （≥3.5 g/24 h） and hypoalbuminemia； patients with estimated glomerular filtration rate （eGFR） <30 mL・min-¹・（1.73 m²）-¹ were excluded. RTX was administered according to the standard regimen （1 g IV on day 0 and 1 g IV at week 2）. Patients were followed at 1， 3， 6 and 12 months after treatment. Clinical parameters monitored included 24‑hour urine protein， serum albumin， and anti‑PLA2R antibody levels. Treatment response was assessed according to the Kidney Disease： Improving Global Outcomes （KDIGO） 2012 guideline criteria.ResultsThe cohort （n=70） had a mean age of 44.89±13.76 years （range 18-78）. Baseline eGFR was 103.58 （14.26， 147.89） mL·min-1·（1.73 m²）-1， serum albumin 24.30（15.32， 33.57） g/L， 24‑hour proteinuria 8.65 （5.43， 26.72） g， and anti‑PLA2R antibody 256.42（177.38， 468.55） RU/mL. At 12 months， 28 patients （40.00%） achieved complete remission， 30 （42.86%） partial remission， yielding an overall remission rate of 82.86%（58/70）. Patients achieving complete remission showed statistically significant improvement across key clinical indices （P<0.05）. Patients in the partial remission group and those showing clinical response without meeting remission criteria also demonstrated continued improvement （P<0.05）. The no‑response group showed no significant changes in measured indices （P>0.05）. No infusion‑related adverse reactions or serious infections were observed during the 12‑month follow‑up.ConclusionIn this cohort of high‑risk， treatment‑naïve IMN patients， rituximab produced rapid onset of effect， high remission rates， and good tolerability over one year， supporting its safety and efficacy as an initial treatment option.

Cognitive impairment is highly prevalent among patients with end-stage renal disease (ESRD), particularly those undergoing dialysis, and is associated with poor clinical outcomes and reduced quality of life. Emerging evidence suggests that Klotho, an anti-aging protein predominantly expressed in the kidney, plays a critical role in the pathophysiology of uremia-related cognitive dysfunction. This review summarizes current clinical and experimental evidence regarding Klotho deficiency in dialysis patients and its association with cognitive impairment. We further discuss the underlying mechanisms, including oxidative stress, chronic inflammation, vascular dysfunction, and blood–brain barrier disruption. In addition, the potential role of Klotho as a biomarker and therapeutic target is critically evaluated. Understanding the kidney–brain axis mediated by Klotho may provide novel insights into early identification and targeted intervention for cognitive impairment in dialysis populations.

Macrophage-mediated inflammatory responses play a critical role in the onset and progression of diabetic kidney disease (DKD), yet the underlying molecular mechanisms remain incompletely understood. In this study, we found that the expression of fatty acid-binding protein 4 (FABP4) was significantly elevated in renal tissues from patients with diabetic kidney disease. Both in vivo and in vitro experiments further demonstrated that under high-glucose and high-lipid conditions, FABP4 activated macrophage-associated inflammation and promoted epithelial-mesenchymal transition (EMT) in HK-2 cells. Mechanistically, FABP4 transported saturated fatty acids into macrophages, activating the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, which subsequently triggered caspase-1/gasdermin D (GSDMD)-mediated pyroptosis and the maturation and release of IL-1β. These inflammatory signals ultimately regulated the EMT process in renal tubular epithelial cells and enhanced the migratory ability of HK-2 cells. Collectively, FABP4 in macrophages is a key regulator of the NLRP3/IL-1β signaling axis, promotes the progression of DKD in mice, and represents a potential molecular target for the treatment of this disease.

BACKGROUND:Diabetic kidney disease (DKD) is a critical microvascular complication of diabetes mellitus, and the current pharmacotherapies are limited by side effects. Medical and edible homology (MEH) Agents: The DKD and healthy control multi- -target active and low-toxic drugs (MEH) agents were identified based on transcriptomic data of DKD patients and healthy controls retrieved in the GEO database. METHODS:The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and other databases were searched to obtain active components of 106 MEH substances. The GraphBAN model was used to predict the compound-target interaction and filter candidate components and genes based on the five rules proposed by Lipinski. A multi-level MEH-Ingredient-Gene-Pathway network was built to discover important active ingredients and hub genes. The protein-protein interaction (PPI) network analysis, immune cell infiltration analysis, molecular docking, and molecular dynamics simulations were further used to validate core interactions. RESULTS:A total of 436 DEGs were identified. Screening via the GraphBAN model generated 6 candidate active ingredients and 11 candidate genes, from which 5 key ingredients (aurantio-obtusin, obtusin, licoisoflavanone, triptolide, triptolidenol) and 3 core genes (CERS6, CETP, FYN) were determined. PPI network analysis suggested that these core genes synergistically regulate lipid metabolism and immune processes. Further evaluation revealed concurrent immune activation and suppression in DKD, with key genes negatively correlated with immune cell infiltration levels. Finally, molecular docking and dynamics simulations verified stable binding affinities of the corresponding complexes. DISCUSSION:The present study investigated the therapeutic potential of multi-target, low-toxicity MEH substances against DKD. Using transcriptomic profiling, compound-- target prediction, and regulatory network construction, we identified 5 key MEH ingredients and 3 core genes. These molecules may stabilize DKD progression via modulating lipid metabolism and immune-inflammatory pathways, providing a basis for the development of multi-target natural products and supporting the value of artificial intelligence in MEH-related research. CONCLUSION:In the current study, the authors examined the anti-DKD effects of MEH agents and identified 5 main ingredients and 3 central genes, which could prevent DKD due to the regulation of lipid metabolism. Some of the limitations, such as a rather limited sample size, must be taken up in future studies.

BACKGROUND:Diabetic kidney disease (DKD) is characterized by tubular EMT and fibrosis. So far, the pathogenesis of DKD is still not fully understood. Pentraxin 3 (PTX3), an inflammatory regulator, is overexpressed in DKD due to hyperglycemia. PTX3 amplifies inflammation by promoting inflammatory cytokine release (TNF-α, IL-6) and activating the nuclear factor kappa-B (NF-κB) pathway. Subsequently, it triggers the c-Jun N-terminal kinase (JNK) signaling pathway, enhancing AP-1-mediated transcription of inflammatory genes (MCP-1, ICAM-1). JNK also upregulates EMT markers (α-SMA, N-cadherin) through increased transforming growth factor TGF-β1, accelerating renal fibrosis. Targeting the PTX3-JNK axis with neutralizing antibodies or inhibitors mitigates inflammation and EMT, suggesting PTX3 as a potential anti-fibrotic target in DKD. OBJECTIVE:We believe that PTX3 induces EMT in HK-2 cells to further lead to fibrosis by activating the JNK signaling pathway. Thus, investigate the role of Pentraxin 3 (PTX3) in diabetic kidney disease (DKD) and explore the therapeutic potential of targeting the PTX3-JNK signaling pathway. METHODS:Human renal tubular epithelial cells (HK-2) were stimulated with high glucose (HG); a DKD mouse model was established using streptozotocin (STZ) induction; and renal biopsy tissues were collected from DKD patients. PTX3 expression was detected by quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting, and immunofluorescence. Recombinant human PTX3 protein (Rh-PTX3) was added to HK-2 cells to examine the expression of EMT markers (E-cadherin, α-SMA, Vimentin, N-cadherin, Snail) and the key JNK pathway molecule (p- JNK). The JNK inhibitor SP600125 was used to assess changes in EMT and fibrosis. In vitro experiments were conducted using human renal tubular epithelial cells (HK-2) stimulated with high glucose (HG) in (The Key Laboratory of Nephrology) facilities. A DKD mouse model was established through streptozotocin (STZ) induction in (C57). Renal biopsy tissues were obtained from DKD patients at (The Second Hospital of Lanzhou University) between (2024-09-01) and (2025-09-01). PTX3 expression was detected by qRT-PCR. Western blotting and immunofluorescence. Recombinant human PTX3 protein (Rh-PTX3) was added to HK-2 cells to examine the expression of EMT markers (E-cadherin, α-SMA, Vimentin, N-cadherin, Snail) and the key JNK pathway molecule (p-JNK). The JNK inhibitor SP600125 was used to assess changes in EMT and fibrosis. Data collection occurred between (2024-09-01) and (2025-09-01). RESULTS:PTX3 expression was significantly increased in the HG cell model and DKD models, accompanied by EMT and JNK pathway activation. The JNK inhibitor reversed the EMT phenotype induced by PTX3 overexpression. DISCUSSION:This study reveals that PTX3 promotes renal fibrosis in DKD by activating the JNK pathway, leading to EMT of renal tubular epithelial cells. This finding, supported by clinical samples, animal models, and cell experiments, suggests PTX3-JNK signaling as a potential therapeutic target for DKD. CONCLUSION:PTX3 promotes renal tubular EMT and fibrosis by activating the JNK signaling pathway. Targeting the PTX3-JNK axis may provide a novel therapeutic strategy for DKD.

Background: The relationship between heavy metals, particularly lead (Pb), and diabetic kidney disease (DKD) remains unclear, especially regarding exposure thresholds. This study investigates the association between blood Pb levels and DKD risk using data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018. Methods: A total of 1,343 participants were included, with 508 diagnosed with DKD. Baseline characteristics were compared between DKD and non-DKD groups. Multivariate generalized linear models (GLMs) and weighted logistic regression were used to assess correlations between blood Pb levels and DKD risk. A nomogram was developed to evaluate the predictive power of significant clinical characteristics. Results: Key clinical characteristics, including age, marital status, and serum Pb levels, differed significantly between DKD and non-DKD groups. Serum Pb was identified as a significant risk factor (ORs: 1.18-1.39, p < 0.01). The nomogram demonstrated good predictive accuracy (AUC = 0.717). Conclusion: Elevated blood Pb levels are significantly associated with DKD, with a non-linear relationship and a defined threshold. These findings highlight the potential role of Pb exposure in DKD pathogenesis and suggest the utility of blood Pb monitoring in diabetic patients.

Objective:Based on the Global Burden of Diseases (GBD) 2021 data, this study systematically analyzed the trends in the disease burden of diabetic kidney disease (DKD) and predicted its burden over the next decade in 204 countries and regions worldwide from 1990 to 2021. Methods:Data on DKD from the GBD study spanning 1990 to 2021 were analyzed for trends using age-standardized rates (ASRs) and average annual percentage change (AAPC). The Joinpoint Regression Model (JRM) was applied to identify turning points, and the Autoregressive Integrated Moving Average (ARIMA) model was used to forecast future trends. Statistical analysis was performed using R software. Results:The age-standardized incidence rate (ASIR) and age-standardized death rate (ASDR) of global DKD from 1990 to 2021 showed substantial increases, with cumulative rises of 55.0% (95% CI: 42.3% to 69.8%, P < 0.001) and 57.3% (95% CI: 43.1% to 73.5%, P < 0.001), respectively. The age-standardized prevalence rate (ASPR) declined by 37.5% (95% CI: －45.2% to －28.8%, P < 0.001), while the age-standardized disability-adjusted life years (DALYs) rate rose by 56.2% (95% CI: 42.8% to 71.5%, P < 0.001). Noticeable disparities in disease burden were observed among countries and regions. Greenland experienced the largest increase in ASPR, whereas the United Kingdom had the most substantial decrease. Estonia had the highest rise in ASIR, while Ireland saw the greatest decline. The United States had the most pronounced increase in ASDR, while the Maldives had the largest decrease. East Asia had the highest number of current cases, while South Asia bore the heaviest burden of new cases and DALYs. The increase was more prominent in regions with a low socio-demographic index (SDI). Projections for the next decade (2022-2031) indicate that the global ASPR of DKD will increase by an average of 0.45% per year (95% CI: 0.21% to 0.69%), the ASIR will decrease by an average of 0.23% per year (95% CI: －0.47% to －0.01%), and the age-standardized DALYs rate will increase by an average of 1.12% per year (95% CI: 0.89% to 1.35%). The overall burden of the disease is expected to continue growing. Conclusion:The global burden of DKD is steadily increasing, and it is especially severe in regions with low SDI. It is essential to implement targeted prevention and control measures in high-burden areas to provide a scientific basis for allocating public health resources.

Aristolochic acids (AAs) are a class of well-known nephrotoxic compounds; however, the molecular mechanisms underlying AA-induced kidney injury remain incompletely understood. This study aimed to identify potential molecular targets and explore the mechanisms involved in AA-induced kidney injury, with particular emphasis on prostaglandin-endoperoxide synthase 2 (PTGS2). An integrated computational and experimental approach was applied. Candidate targets associated with AA exposure and kidney injury were identified through database mining, followed by enrichment and network analyses to determine key regulatory genes. Molecular docking and molecular dynamics simulations were performed to evaluate AA-target interactions, and the association between PTGS2 and kidney injury was further assessed using two-sample Mendelian randomization based on genome-wide association study data. Experimental validation was conducted in an acute AAI-induced C57BL/6 mouse model through evaluation of renal function, histopathology, and PTGS2 expression. PTGS2 was identified as a central candidate gene associated with AA-induced kidney injury and exhibited stable binding with AA in silico. In vivo, AAI exposure caused renal dysfunction and histopathological alterations accompanied by reduced PTGS2 expression. These findings identified PTGS2 as a candidate molecular target involved in AA-induced kidney injury and provided a foundation for further mechanistic research.

Robot-assisted partial nephrectomy (RAPN) is an important nephron-sparing approach for renal tumors, with increasing emphasis on postoperative renal functional preservation. Preservation of renal function is clinically relevant in patients with reduced renal reserve or factors associated with future renal decline. However, the global research landscape and emerging trends in this field remain unclear. This study performed a bibliometric analysis of publications related to robot-assisted partial nephrectomy and renal function preservation, with emphasis on functional outcomes and CKD-related concepts identified within the literature. Publications from 2008 to 2026 were retrieved from the Web of Science Core Collection on May 10, 2026. Only English-language articles and reviews were included. Data were analyzed using Excel, VOSviewer, CiteSpace, Charticulator, and Scimago Graphica. A total of 276 publications were included, comprising 245 articles and 31 reviews. Publication output showed steady growth, with peaks in 2017 and 2022. Urology and nephrology were the dominant category. The United States led in publications, citations, and H-index, followed by Italy and China, with collaboration centered mainly on the United States and Italy. Cleveland Clinic and Temple University were leading institutions. Keyword analysis identified partial nephrectomy, ischemia, warm ischemia time, eGFR, small renal mass, and trifecta as major themes. The field has evolved from technical exploration toward ischemia reduction, nephron preservation, standardized outcome reporting, and individualized risk stratification. Future studies should prioritize prospective multicenter designs and standardized renal functional endpoints.

Background: Acute kidney injury (AKI) is a severe clinical syndrome characterized by metabolic stress and profound inflammation. However, the landscape of lactylation-associated molecular alterations and their potential relevance in AKI remain incompletely understood. Methods: Bulk transcriptomes (GSE30718) were analyzed using the limma package, weighted gene co-expression network analysis (WGCNA), and consensus clustering to characterize AKI-associated molecular patterns linked to lactylation-associated signatures. Hub genes, prioritized through least absolute shrinkage and selection operator (LASSO) regression and the random forest algorithm, were integrated into a diagnostic nomogram and evaluated in an external cohort (GSE139061). Immune infiltration analysis was performed, and single-cell RNA sequencing data (GSE183276) were used to resolve cell-type-specific expression patterns of the hub genes. A cisplatin-induced murine AKI model validated global protein lactylation and hub gene expression by immunohistochemistry and Western blot. Results: Three hub genes (CKLF, ACLY, and SLC13A3) reliably discriminated AKI from controls (training AUC = 0.897). Their diagnostic performance varied in the external validation cohort. These genes correlated significantly with diverse immune infiltrates. Single-cell analysis localized CKLF predominantly to immune cells, ACLY broadly across renal populations, and SLC13A3 to proximal tubules. In vivo validation demonstrated increased global protein lysine lactylation levels in injured kidneys and confirmed expression alterations of CKLF, ACLY, and SLC13A3 consistent with transcriptomic observations. Conclusions: Integrating transcriptomic analysis with in vivo experimental validation, this study identified CKLF, ACLY, and SLC13A3 as candidate lactylation-associated signatures linked to immune and metabolic alterations in AKI.

BACKGROUND:Dysbiosis of Intestinal Flora Lipopolysaccharides (LPS) is implicated in Diabetic Nephropathy (DN), yet the underlying mechanisms remain unclear. This study aims to elucidate the causal relationship between bacterial LPS and DN, with the goal of informing targeted therapeutic strategies. METHODS:DN datasets GSE30528 and GSE96804 were analyzed. Bacterial LPS-related genes (LPS-RGs) were retrieved from the Gene Set Enrichment Analysis (GSEA) database. Differential expression analysis identified differentially expressed genes (DEGs), which were cross-referenced with LPS-RGs to derive DE-LPS-RGs. Mendelian randomization (MR) was applied to explore correlations between exposure factors and outcomes using GWAS data. miRNA-mRNA and TFmRNA regulatory networks were constructed using data from the TarBase and ENCODE databases, and potential therapeutic agents were identified through the DGIdb database. RESULTS:Seven DE-LPS-RGs were identified, with CD14 and LY86 selected as biomarkers. GSEA and GeneMANIA analyses indicated that these genes participate in signal transduction and chargelike receptor signaling pathways. The regulatory networks demonstrated that LY86 interacts with miRNA hsa-mir-26a-5p, while TF ELK1 regulates both CD14 and LY86. Additionally, CD14 was associated with three potential drugs: VB-201, IC14, and Lovastatin. CONCLUSION:CD14 and LY86 represent promising biomarkers for DN, offering new perspectives for its prediction, diagnosis, and therapeutic intervention.

This study aims to compare the perioperative, functional, and oncological outcomes of robot-assisted partial nephrectomy in complex renal masses (CRM) with non-CRM tumors. A systematic literature review was conducted in PubMed, Embase, Web of Science, and Cochrane Library databases, following the PRISMA guidelines. The studies comparing RAPN outcomes between complex renal masses (CRM), specifically completely endophytic and hilar renal tumors, versus non-complex renal masses (non-CRM), which include non-endophytic, and non-hilar renal tumors. Twelve studies involving 8126 patients were analyzed. The results revealed CRM group increased operative time (Mean Difference [MD]: 14.35 min; 95

Diabetic kidney disease (DKD) is a frequent microvascular complication of diabetes and the predominant cause of end-stage renal disease worldwide. Dysregulated microRNA (miRNA) expression contributes to DKD pathogenesis. This study aimed to determine the clinical significance of serum exosomal miR-1207-5p expression in type-2 DKD. Serum exosomes were isolated from 51 DKD patients stratified into low-, medium-, high-, and extremely high-risk groups and 11 control individuals. Exsosomal miR-1207-5p expression was determined by real-time-quantitative polymerase chain reaction (RT-qPCR), and its relationship with the patient’s clinical records was explored. Bioinformatics analyses were performed to determine miR-1207-5p target genes using tools available online. Datasets obtained from the Gene Expression Omnibus (GEO) database were used to validate the experimental results. miR-1207-5p was downregulated in the DKD patients compared to the controls, and this downregulation was the most prominent in the high-risk group. Correlation analysis revealed inverse associations between miR-1207-5p and parameters of renal dysfunction. Multivariate logistic regression indicated that miR-1207-5p may confer protection against DKD progression. Receiver operating characteristic (ROC) curve analysis demonstrated the ability of exosomal miR-1207-5p to distinguish low- versus high-/extremely high-risk DKD. Bioinformatics approaches identified a miR-1207-5p-mediated competing endogenous RNA (ceRNA) network with connections to pathogenic pathways. Serum exosomal miR-1207-5p holds promise as a noninvasive biomarker for assessing DKD progression risk and improving the diagnosis and prognosis of affected patients.

This investigation sought to examine the clinical and pathological characteristics, outcomes, and risk factors linked to the progression of renal function in adult-onset immunoglobulin A (IgA) vasculitis within a single center in northwest China. Data were retrospectively gathered from cases of adult-onset IgA vasculitis recorded at a tertiary hospital in northwest China, covering the period from January 2013 to August 2024. During the follow-up, clinical information was compared between patients who advanced to chronic kidney disease (CKD) stage 3 and those who did not. A sum of 1082 adult-onset IgA vasculitis patients (632 men; median age of 37 years) were included. Among patients with baseline proteinuria >0.5 g/24h (43.9

The principal vascular access options for hemodialysis are arteriovenous fistula （AVF）， arteriovenous graft （AVG）， and central venous catheter （CVC）. Each access type differs in effectiveness， safety， and durability. This review integrates recent advances from clinical trials， biomaterials research， and device innovation to clarify their respective roles， advantages， and limitations. We examine emerging pharmacological approaches， novel materials， device designs， and cutting-edge technologies， with special emphasis on structural and mechanical considerations. The goal is to trace the evolving landscape of vascular access strategies and highlight their pivotal role in improving care for patients undergoing hemodialysis.

Background To investigate the correlation between Ets-1 and the progression of diabetic kidney disease (DKD). Methods A total of 115 patients with biopsy-proven DKD were followed for three years. Based on renal function after follow-up, they were categorized into a progress group (PG, 57.4%, 66/115) and a relatively stable group (RSG, 42.6%, 49/115). Ets-1 expression in renal tissue was analyzed, along with its associations with clinical, biochemical, and pathological parameters, and its predictive value for DKD progression. Results Ets-1 expression differed significantly between PG and RSG (p < 0.01). Its expression strongly correlated with clinical indicators of kidney injury (e.g., proteinuria, serum creatinine, blood pressure) and systemic inflammation (CRP) (all p < 0.01), and inversely with estimated eGFR (p < 0.01). Importantly, Ets-1 showed strong positive correlations with all renal pathological scores (glomerular, tubulointerstitial, vascular lesions) and expression of the EMT marker α-SMA (all r > 0.7, p < 0.01). Binary logistic regression confirmed that Ets-1 expression, UAER, 24-hour UTP, and serum creatinine were independent risk factors for DKD progression. ROC analysis demonstrated high predictive value of Ets-1 for DKD progression (AUC = 0.875), comparable to that of UAER (AUC = 0.874). Conclusion Ets-1 is closely associated with DKD progression and may serve as a potential predictor for disease advancement in clinical practice.

The relationship between low back pain (LBP) and diabetes mellitus (DM) remains inconclusive, with no prior meta-analysis specifically evaluating risk factors for DM in patients with LBP. A comprehensive search of PubMed, Web of Science, Embase, and Cochrane Library databases was conducted. Eligible studies explicitly reported risk factors for LBP and DM. Demographic data were extracted, and meta-analyses were performed using random- or fixed-effects models, with statistical analyses conducted in Review Manager (RevMan) 5.4 software. A total of 21 studies involving 346,380 patients were included. The prevalence of DM in patients with LBP was 27

Diabetic kidney disease (DKD), a prominent microvascular complication of diabetes mellitus and the leading cause of end-stage renal disease (ESRD), was addressed through a novel nanotherapeutic approach. This study engineered folic acid-conjugated poly(lactic-co-glycolic acid) nanoparticles (FA-PLGA NPs) for the folate receptor (FR)-targeted delivery of Toll-like receptor 4 small interfering RNA (TLR4 siRNA) to treat diabetic nephropathy (DN). In a streptozotocin-induced DN murine model, administration of FA-PLGA NPs/TLR4 siRNA significantly mitigated renal injury compared to untreated DN controls. This was evidenced by reduced mesangial matrix expansion, downregulation of TLR4/CD86/FLOR2 expression, decreased urinary protein excretion, and lowered circulating IL-6 and TNF-α levels. Importantly, renal function parameters, including urea nitrogen, serum creatinine, and albumin) were restored to near-normal levels. These results demonstrate that FRβ-targeted TLR4 siRNA delivery via FA-PLGA NPs effectively reduces inflammation and renal damage, establishing a promising novel therapeutic strategy for DN.

BACKGROUND:Diabetes mellitus (DM) frequently results in Diabetic Nephropathy (DN), which has a significant negative impact on the quality of life of diabetic patients. Sphingolipid metabolism is associated with diabetes, but its relationship with DN is unclear. Therefore, screening biomarkers related to sphingolipid metabolism is crucial for treating DN. METHODS:To identify Differentially Expressed Genes (DEGs) in the GSE142153 dataset, we conducted a differential expression analysis (DN samples versus control samples). The intersection genes were obtained by overlapping DEGs and Sphingolipid Metabolism-Related Genes (SMRGs). Furthermore, The Least Absolute Shrinkage and Selection Operator (LASSO) and Support Vector Machine Recursive Feature Elimination (SVM-RFE) algorithms were used to filter biomarkers. We further analyzed the Gene Set Enrichment analysis (GSEA) and the immunoinfiltrational analysis based on biomarkers. RESULTS:We identified 2,186 DEGs associated with DN. Then, five SMR-DEGs were obtained. Subsequently, biomarkers associated with sphingolipid metabolism (S1PR1 and SELL) were identified by applying machine learning and expression analysis. In addition, GSEA showed that these biomarkers were correlated with cytokine cytokine receptor interaction'. Significant variations in B cells, DCs, Tems, and Th2 cells between the two groups suggested that these cells might have a role in DN. CONCLUSION:Overall, we obtained two sphingolipid metabolism-related biomarkers (S1PR1 and SELL) associated with DN, which laid a theoretical foundation for treating DN.