BACKGROUND:Idiopathic membranous nephropathy (IMN) is a major cause of nephrotic syndrome and end-stage renal disease, but the gold-standard diagnostic method is invasive. This study aims to develop a non-invasive diagnostic model for IMN, focus on the diagnostic value of anti-phospholipase A2 receptor antibody (anti-PLA2R-Ab). PATIENTS AND METHODS:In this single-center retrospective study,we included 9524 patients with chronic kidney disease patients who received renal biopsies, extracted 139 clinicopathological data from their records, and divided them into two groups based on pathological results.Renal biopsy cases were collected to form an independent external validation cohort.Seven machine learning methods were used to develop and verify models, and anti-PLA2R-Ab data were used to optimize and evaluate these models. Seventy percent of the patients were used for training, and the other 30% for verification. The area under the receiver operating characteristic curve, F1-score, accuracy, and confusion matrix were used to evaluate the diagnostic performance of the models. RESULTS:We analyzed 8840 patients and 10 indicators, excluding anti-PLA2R-Ab, to develop and validate diagnostic models, and then analyzed 2457 patients and 6 indicators, including anti-PLA2R-Ab, to develop and validate optimized models. With or without anti-PLA2R-Ab, the CatBoost model provided more accurate diagnosis of IMN (internal vs. external verification AUC:0.921 vs.0.901 and 0.950 vs.0.904, respectively) than anti-PLA2R-Ab alone (AUC: 0.867). CONCLUSION:The CatBoost model was an accurate and non-invasive method that provided better diagnosis of IMN than anti-PLA2R-Ab in Chinese patients. This model is especially when anti-PLA2R-Ab testing and kidney biopsy are difficult or impossible.

The relationship between kidney function and mortality in centenarians, particularly with respect to hormonal regulation, remains unclear. This study investigated the association between estimated glomerular filtration rate (eGFR) and all-cause mortality in female centenarians and explored the potential role of testosterone. Within the China Hainan Centenarian Cohort Study, 701 female centenarians (median age: 102 years) were enrolled. eGFR was calculated using the CKD-EPI 2009 creatinine equation. Restricted cubic splines (RCSs) and multivariable Cox proportional hazards models were employed to assess nonlinear associations. Likelihood ratio tests were used to evaluate the interaction effect of testosterone. During a median follow-up of 31 months, 643 participants (91.7

BACKGROUND:During the progression of immunoglobulin A nephropathy (IgAN), residual nephrons compensate for nephron loss by increasing single-nephron estimated glomerular filtration rate (eGFR). This adaptive hyperfiltration may accelerate the decline in kidney function. However, due to measurement challenges, the prognostic value of single-nephron eGFR remains unclear. This study investigates its impact on kidney function decline in patients with IgAN. METHODS:This observational cohort study included 187 biopsy-confirmed IgAN patients who had undergone computed tomography and biopsy during their hospitalization. Single-nephron eGFR was estimated by dividing total eGFR by nephron number, the latter of which was derived from the cortical volume and glomerular density. The primary composite outcome was kidney function decline, defined as a sustained annual eGFR decrease of ≥5 mL/min/1.73 m2, a ≥40% reduction in eGFR from baseline or end-stage renal disease. Cox proportional hazards models were fit to estimate associations between single-nephron eGFR and kidney function decline. RESULTS:Among the 187 participants (45% women, mean age 38 ± 11 years), 57 experienced a decline in kidney function over a median follow-up period of 3.1 years. Participants were divided into three groups based on their single-nephron eGFR. Kaplan-Meier analysis demonstrated significantly reduced kidney survival in the high single-nephron eGFR group compared with the low and middle groups (log-rank P < .001). Compared with the low single-nephron eGFR group, multivariable hazard ratios for kidney function decline were 2.50 (95% confidence interval 1.10-5.67; P = .03) for the middle group and 5.30 (2.44-11.54; P < .001) for the high group. CONCLUSIONS:A higher single-nephron eGFR is identified as a risk factor for kidney function decline in patients with IgAN, which supports its potential as an early risk-stratification tool. Moreover, using eGFR cutoffs alone to define hyperfiltration may lead to misclassification due to its inability to distinguish patients with hyperfiltration from those without.

Abstract Objectives To validate blood oxygen level-dependent MRI (BOLD-MRI) for non-invasive discrimination of diabetic nephropathy (DN) vs non-diabetic renal disease (NDRD) and prediction of end-stage renal disease (ESRD) in diabetic kidney disease (DKD). Materials and methods A prospective cohort of 133 biopsy-proven DKD patients underwent BOLD-MRI. The semi-automated 12-layer concentric-objects method was used to analyze BOLD-MRI variables. Prognostic markers for ESRD were identified using univariate and multivariate Cox regression. Feature importance was used to select key diagnostic variables and establish logistic regression and machine-learning differential diagnosis models. Results Among 133 patients (44 DN, 55 NDRD, 34 combined), 20 (15.5%) progressed to ESRD over a mean of 21.8 months. Higher renal medullary R2* (MR2*) (> 24 1/s) reduced ESRD risk by 52% (HR, 0.48) in DKD. Prognostic models integrating pathological grouping, hemoglobin levels, and cysC levels achieved a c-index of 0.90. For the DN and combined groups, MR2*, glomerular grading, interstitial lesions, interstitial fibrosis, and tubular atrophy were predictive of ESRD, with a c-index of 0.91. For differential diagnosis, the random forest (RF) model achieved an AUC of 0.901, with diabetic retinopathy, diabetes duration, albumin, blood urea nitrogen, MR2*, hypertension, and glycosylated hemoglobin as the most contributing factors. For the combined group classified as DN, the AUC of the RF model was 0.791; when classified as NDRD, the AUC was 0.856. Conclusion MR2* shows potential value as a non-invasive diagnostic and prognostic tool in the assessment of DKD. However, BOLD-MRI remains a promising yet exploratory technique that requires external validation and interventional studies before clinical implementation. Critical relevance statement Blood oxygen level-dependent-MRI-derived renal medullary R2* robustly predicts ESRD risk and distinguishes DN without biopsy, offering an immediately translatable, non-invasive biomarker for the precision management of DKD in routine nephrology practice. Trial registration ClinicalTrials.gov, NCT03865914. Key Points Blood oxygen level-dependent-MRI medullary R2*(MR2*) > 24 s− 1 halves DKD ESRD risk (HR 0.48). MR2* integrated with clinical variables drives c-index to 0.90 for ESRD prognosis. RF leveraging MR2* and clinical traits attains an AUC of 0.901 for diagnosing DN. Graphical Abstract

BACKGROUND:To investigate the impact of area socioeconomic deprivation on the risk of major adverse kidney events (MAKEs) within 90 days post-discharge among patients with acute kidney injury (AKI). METHODS:This retrospective cohort study included patients with AKI between January 1, 2014, and December 31, 2023. Area socioeconomic deprivation index was calculated using principal component analysis based on district-level economic and healthcare resource data from patients' registered residential areas. Patients were stratified into four deprivation quartiles (Q1-Q4) and analyzed with multivariable Cox proportional hazards regression models to assess the association between deprivation index and MAKE risk. RESULTS:Among 5,934 AKI patients, 1,107 (18.7%) experienced MAKEs within 90-day follow-up. Multivariable Cox regression analysis revealed that patients in the highest deprivation quartile (Q4) had a significantly greater risk of MAKEs than those in the lowest deprivation quartile (Q1) (hazard ratio [HR] 1.48, 95% CI: 1.24-1.77), with a significant dose-response relationship between MAKE risk and (trend p < 0.001). Subgroup analysis revealed that the negative effect of area socioeconomic deprivation was more pronounced among patients with lower levels of health insurance coverage (resident medical insurance/Self-pay) (interaction p = 0.032). Mediation analysis indicated that the delay between discharge and the first outpatient follow-up mediated approximately 23.2% of the area socioeconomic deprivation effect. CONCLUSION:Area socioeconomic deprivation is a key socioenvironmental determinant of outcome in AKI patients. This finding suggests a significant association of macrolevel social environments on disease outcomes. Therefore, social environment assessments should be integrated into AKI clinical management systems for systematically reducing health inequalities.

The extent of the inflammatory response in the early stages of acute kidney injury (AKI) significantly influences renal damage, repair, and ultimately prognosis. Macrophages are key drivers of early inflammation in AKI, and their metabolic reprogramming is closely associated with their pro-inflammatory polarization. However, the mechanisms underlying this process remain incompletely understood. In this study, we combined single-cell RNA sequencing, metabolomics, and gene-editing approaches to, investigate how injured renal tubular epithelial cells regulate macrophage metabolism and phenotype in ischemia-reperfusion injury (IRI)-induced AKI. We found that injured proximal tubular cells secrete high levels of secreted phosphoprotein 1 (SPP1), which binds to CD44, a receptor abundantly expressed on infiltrating macrophages, thereby activating the downstream PI3K/AKT signaling pathway. This activation induces nuclear translocation of PKM2, a key metabolic enzyme, which drives glycolytic metabolic reprogramming in macrophages and promotes their polarization toward a pro-inflammatory phenotype. In vitro and in vivo functional experiments further confirmed that blocking the SPP1-CD44 axis, using siRNA, neutralizing antibodies, or conditional knockout strategies, effectively alleviates renal IRI in mice, reduces macrophage infiltration, and diminishes the inflammatory response. Overall, this study delineates a novel mechanism in which injured tubular cell-derived SPP1 communicates with macrophage CD44 to regulate immunometabolism and inflammatory polarization via the PI3K/AKT-PKM2 signaling module at the single-cell and metabolic levels. These findings provide both a potential therapeutic target and a mechanistic framework for the prevention and treatment of AKI.

Whether IgA nephropathy (IgAN) in patients with systemic lupus erythematosus (SLE) represents a coincidental comorbidity or a distinct clinico-pathological entity remains unclear. This study aimed to characterise the demographic, clinical, pathological, and prognostic features of this rare association. We conducted a systematic review of the PubMed and Embase databases to 31 May 2025 were conducted to identify all reported cases of biopsy-proven IgAN in patients with SLE, excluding cases with concomitant thrombotic microangiopathy, negative Gd-IgA1 immunostaining, prior IgA vasculitis, or ANA-negative disease. Study quality was assessed using the JBI checklist. Individual patient data were pooled; descriptive statistics summarized clinical features, and group comparisons were performed using Mann-Whitney U and Fisher’s exact tests. Individual patient data were extracted and analyzed as a single cohort. Renal outcomes were defined as either a ≥ 40

The circadian rhythmicity of urinary solute excretion is a hallmark of intact renal physiology, yet its disruption in chronic kidney disease (CKD) lacks a practical quantitative tool. We developed the novel Circadian Rhythm Disruption Index (CRDI) to objectively quantify this disruption from routine clinical data and investigated its association with estimated glomerular filtration rate (eGFR) in primary glomerular diseases. This cross-sectional study prospectively enrolled 81 inpatients with biopsy-confirmed primary glomerular diseases under standardized hospital protocols. All spontaneous urine samples over 24-hours were collected. The presence of circadian rhythms in urinary excretion was validated by cosinor analysis. CRDI metrics were defined and developed to calculate protein, creatinine, and volume. Multivariable linear regression was used to examine the CRDI-eGFR relationship, adjusting for demographics, pathology, and medications. Clinical utility was assessed using ROC and decision curve analysis. Significant circadian rhythms were confirmed for all biomarkers. The CRDI for creatinine (CRDI_cr) demonstrated the strongest independent inverse association with eGFR after full adjustment (β = -4.45 mL/min/1.73m2 per unit, p = 0.008). A key finding was the pathological specificity of this relationship; it was most pronounced in IgA nephropathy. Incorporating CRDI_cr into a clinical model improved the AUC for identifying eGFR ≤60 mL/min/1.73m2 from 0.748 to 0.800 and yielded a significant net reclassification improvement (NRI = 0.237). The CRDI effectively quantifies relative circadian disruption. CRDI_cr is independently associated with renal function in a pathology-specific manner, highlighting its potential as a novel biomarker for refined risk stratification in specific glomerular diseases, particularly IgA nephropathy.

Background Diabetic kidney disease (DKD) is a common condition with few treatment options, and inflammation plays a pivotal role in its progression. Luteolin, a natural compound found in traditional Chinese herbs, is known for its anti-inflammatory properties, making it a potential treatment for DKD. But its effect and mechanisms in DKD remain incompletely elucidated. Methods Renoprotective effects of luteolin in db/db mice were assessed with BUN, Scr, uACR, and PAS staining. Flow cytometry and extraction of total membrane proteins were conducted to examine the abundance of full-length TREM2 on the membrane of macrophages. Co-culture of differentially treated macrophages and HK2 cells evaluated luteolin’s impact on efferocytosis. The molecular target of luteolin was elucidated through virtual molecular analysis, SPR, and ADAM10 activity assays. Results Luteolin reduced uACR, BUN, and SCr levels. Histologic analyses showed decreases in mesangial matrix, glomerular volume, GBM thickness, and foot process effacement. Tubular injury scores and KIM1 expression were lowered, while megalin and cubilin expression increased. Renal macrophage infiltration, iNOS+ cells, and IL-1β, IL-18, TNF-α, and MCP-1 levels were reduced. Luteolin elevated TREM2+ macrophages with decreased sTREM2 in vivo and in vitro. Immunofluorescence confirmed increased TREM2+ macrophages and enhanced full-length TREM2 on cell membrane. Luteolin exhibited dose-dependent binding to ADAM10 and inhibited its activity without affecting ADAM10 expression. In co-culture system, luteolin increased p-DAP12, p-SYK, and PHrodo+ cell counts. Apoptotic cells in kidney tissue decreased, while Rab5a and Rab7a expression were upregulated. Conclusions Luteolin attenuates immunoinflammation and pathological injury in db/db mice by enhancing the efferocytosis of apoptotic renal tubular cells by TREM2+ macrophages. The potential mechanism of luteolin involves binding to ADAM10 and inhibiting its activity, which attenuates aberrant shedding of full-length TREM2 from macrophages and potentiates downstream TREM2 signaling. Collectively, luteolin provides a promising option for ameliorating immune inflammation in DKD, demonstrating strong translational potential.

Ferroptosis is a non-apoptotic form of cell death characterized by cellular accumulation of iron-dependent lipid peroxidation. In recent years, a series of studies have proved that ferroptosis participate in the progression of chronic kidney disease (CKD). Notably, cognitive dysfunction is commonly found in CKD patients and it has been recognized as one of CKD pathological features. However, the character of ferroptosis in CKD related cognitive dysfunction remains unclear. This study aims to verify if ferroptosis participates in the CKD related cognitive dysfunction and the underlying mechanism. Then we use Fer-1 and Erastin to explore the effects of ferroptosis on cognition changes in CKD rat. RNA-seq analysis identified ferroptosis related lipid metabolism was significantly changed in CKD rats and the DEGs played an important role in oligodendrocyte differentiation, which were correlated with cognition ability. Fer-1 ameliorated the ultrastructure of hippocampal CA1 region and rescued the myelin sheath injury in CKD rats. Specifically, Fer-1 increased the density of myelinated axons and upregulated the levels of MBP and SOX10 in hippocampus of CKD rats. Notably, Fer-1 decreased the expression of Sirt2 and the AAV-Sirt2 abrogated the beneficial effects of Fer-1 on ferroptosis and myelin sheath in the hippocampus of CKD rats. This study provides a new strategy for improving cognitive dysfunction in CKD.

BACKGROUND:Renal fibrosis is a common pathological feature of chronic kidney disease (CKD) but its underlying mechanisms remain incompletely understood. Our previous study demonstrated that insulin-like growth factor-binding protein 5 (IGFBP-5) promotes glycolytic reprogramming in vascular endothelial cells (ECs) and exacerbates renal inflammation in diabetic kidney disease. METHODS:Human renal proximal tubular epithelial cells (HK-2) and human umbilical vein endothelial cells (HUVECs) were used. A co-culture system was employed to investigate endothelial cell-tubular epithelial cell (EC-TEC) crosstalk. Unilateral ureteral obstruction (UUO) and aristolochic acid nephropathy (ANN) models were established in wild-type (WT), global IGFBP-5-/- and endothelial-specific Tie-2 Cre;IGFBP-5-/- mice. Expression levels of IGFBP-5, TGF-β1 and fibrosis markers were assessed to investigate the role of IGFBP-5 in renal fibrogenesis. RESULTS:Serum IGFBP-5 levels were significantly elevated in patients with CKD. Genetic ablation of IGFBP-5 attenuated renal fibrosis in murine models, demonstrating its critical role in fibrogenesis. IGFBP-5 was predominantly expressed in ECs and endothelial-specific deletion delayed renal fibrosis progression via suppression of the TGF-β1/Smad3 pathway. In vitro, endothelial-derived IGFBP-5 promoted a profibrotic phenotypic transformation in TECs through AKT-mediated phosphorylation of the TGF-β1/Smad3 axis. Conversely, TGF-β1 stimulated IGFBP-5 biosynthesis and secretion in ECs via the ERK signalling pathway, establishing a self-amplifying feedback loop. This reciprocal IGFBP-5/TGF-β1 crosstalk between ECs and TECs was confirmed in co-culture experiments. CONCLUSION:Our findings reveal a novel EC-TEC crosstalk axis mediated by reciprocal IGFBP-5/TGF-β1 signalling, which is a critical driver of renal fibrosis. IGFBP-5 emerges as a promising therapeutic target for inhibiting renal fibrogenesis in CKD.

Introduction: SGLT2 inhibitors reduce renal composite endpoints and proteinuria, yet RCTs uniformly show an acute eGFR dip within 2 weeks to 2 months after initiation. However, demographic and clinical predictors of an acute eGFR dip demonstrate considerable heterogeneity across studies. This study aims to identify urinary protein biomarkers of this early eGFR dip and integrate them with routine variables to build a clinically actionable prediction model. Methods and analysis: This three-stage proteomics study includes retrospective discovery, prospective internal validation, and external validation cohorts (total n ≈ 600–700). DIA mass spectrometry will screen for urinary proteins associated with ≥10% eGFR decline at 1 month post-SGLT2i initiation in CKD stages 3–4. Top candidates (FDR < 10%, FC > 1.5, ion intensity > 1 × 104, unique gene families) will be validated by ELISA. A LASSO-logistic regression model will integrate the top three proteins with seven routinely available clinical variables: age, BMI, diabetes status, heart failure, systolic blood pressure, baseline eGFR, and diuretic use. Model performance will be assessed using the C-statistic, NRI, IDI, and calibration metrics. Adaptive stopping rules are pre-specified. Ethics and dissemination: Approved by the Ethics Review Committee at Chinese PLA General Hospital (S2025-859-02, 2025KY126-KS002), all participants will provide written informed consent prior to enrollment, and the study will adhere to the Declaration of Helsinki. Data will be pseudonymized and stored securely according to institutional regulations. Findings will be published in peer-reviewed journals and presented at international nephrology conferences. Trial Registration: Registered Report Identifier: ChiCTR2600119772. Date of registration: 3 March 2026.

Introduction:Sodium-glucose cotransporter 2 inhibitors (SGLT2is) are crucial in managing proteinuria in chronic kidney disease (CKD), yet individual responses vary. Whether urinary glucose excretion, a direct pharmacodynamic marker of SGLT2is, could predict proteinuria reduction efficacy remains unclear and has not been specifically investigated. Methods:We enrolled 277 CKD patients treated with empagliflozin (10 mg/day) between July 2024 and September 2025 at a single center, stratifying them into low (<46.4 mmol/L, n = 69) and high (≥46.4 mmol/L, n = 208) urinary glucose groups by 24-h urinary glucose levels after 3 months of treatment. We evaluated changes in proteinuria levels following 3 and 6 months of medication across the different urinary glucose groups. Changes in laboratory values over time were analyzed using paired Wilcoxon signed-rank tests. Results:Proteinuria was significantly reduced at both 3 (-0.42 g/24 h [95% confidence interval [CI]: -0.55 to -0.32]) and 6 months (-0.46 g/24 h [95% CI: -0.61 to -0.33]) after treatment initiation. After adjusting for covariates, urinary glucose excretion predicted proteinuria reduction from 3 to 6 months (β = 2.47, 95% CI: 0.49-4.45, p = 0.015), with higher urinary glucose correlating with greater proteinuria decline. The high urinary glucose group had significant proteinuria reduction from baseline at 3 and 6 months (p < 0.001), unlike the low group. Following propensity score adjustment for age, sex, body mass index, baseline estimated glomerular filtration rate (eGFR), and renin-angiotensin-aldosterone system inhibitors use, the high urinary glucose group had a significantly higher relative risk of ≥30% proteinuria reduction (risk ratio = 2.82, 95% CI: 1.20-6.65, p = 0.017), particularly in patients with baseline proteinuria ≥1 g/24 h. Urinary glucose concentration was weakly positively correlated with 6-month eGFR change (r = 0.17, p = 0.011). Conclusions:Urinary glucose concentration can serve as a predictor of SGLT2i-mediated proteinuria reduction, providing a practical clinical reference for personalized CKD management.

Introduction： Sodium-glucose cotransporter 2 inhibitors (SGLT2is) are crucial in managing proteinuria in chronic kidney disease (CKD), yet individual responses vary. Whether urinary glucose excretion, a direct pharmacodynamic marker of SGLT2is, could predict proteinuria reduction efficacy remains unclear and has not been specifically investigated. Methods： We enrolled 277 CKD patients treated with empagliflozin (10mg/day) between July 2024 and September 2025 at a single center, stratifying them into low (<46.4 mmol/L, n=69) and high (≥46.4 mmol/L, n=208) urinary glucose groups by 24-hour urinary glucose levels after 3 months of treatment. We evaluated changes in proteinuria levels following 3 and 6 months of medication across the different urinary glucose groups. Changes in laboratory values over time were analyzed using paired Wilcoxon signed-rank tests. Results： Proteinuria was significantly reduced at both 3 [−0.42 g/24 h (95% CI −0.55 to −0.32)] and 6 months [−0.46 g/24 h (95% CI −0.61 to −0.33)] after treatment initiation. After adjusting for covariates, urinary glucose excretion predicted proteinuria reduction from 3 to 6 months (β=2.47, 95% CI: 0.49-4.45, p=0.015), with higher urinary glucose correlating with greater proteinuria decline. The high urinary glucose group had significant proteinuria reduction from baseline at 3 and 6 months (p<0.001), unlike the low group. Following propensity-score adjustment for age, sex, and Body Mass Index (BMI), baseline estimated glomerular filtration rate (eGFR), and renin-angiotensin-aldosterone system (RAAS) inhibitors use, a significantly higher relative risk of ≥30% proteinuria reduction in the high urinary glucose group (RR=2.82, 95% CI: 1.20-6.65, p=0.017), particularly in patients with baseline proteinuria ≥1g/24h. Urinary glucose concentration was weakly positively correlated with 6-month eGFR change (r=0.17, p=0.011). Conclusions： Urinary glucose concentration can serve as a predictor of SGLT2i-mediated proteinuria reduction, providing a practical clinical reference for personalized CKD management.

Lupus nephritis (LN), the most severe complication of systemic lupus erythematosus (SLE), arises from systemic immune dysregulation and renal damage. While renal immune perturbations are well-studied, systemic signatures specific to LN pathogenesis remain unclear. Integrated single-cell RNA and immune repertoire analysis of 177,259 peripheral blood mononuclear cells (PBMCs) from healthy donors and SLE patients (including active LN and non-nephritis controls) revealed LN-specific circulating immune signatures, including κ light-chain preference in naive B cells and distinct clonal expansion in CD8+ effector T cells. These clonally expanded CD8+ effector T cells exhibited transcriptional variations indicating increased migratory capacity and exhaustion, along with preferential usage of TRBV genes (TRBV27/TRBV15/TRBV7-9), which have enhanced binding potential to an EBV epitope GLCTLVAM. Based on these findings, we developed a dual-biomarker model demonstrating reliable LN diagnosis (AUC = 0.895). Cross-tissue analysis confirmed concordance between peripheral and intrarenal immune perturbations, supporting non-invasive blood-based monitoring. Enhanced MIF-(CD74 + CXCR4) axis activity linked to lymphocyte activation/migration, while CD74+ memory B cells upregulated MHC-I antigen presentation. Renal immunostaining revealed CD74+ B cells proximal to CD8+ T cell infiltrates, suggesting CD74-mediated crosstalk facilitates intrarenal T cell activation. This study provides an integrated LN immune atlas, identifies translatable biomarkers and highlights CD74 as a potential therapeutic target. Integrated single-cell RNA and immune repertoire analysis of PBMCs identifies key circulating immune perturbations in lupus nephritis, highlighting non-invasive biomarkers and CD74 as a potential therapeutic target.

Infection is a leading cause of mortality in patients with systemic lupus erythematosus (SLE), yet effective tools for early identification of high-risk patients are lacking. This study aimed to develop an explainable machine learning (ML) model to predict in-hospital infection risk among SLE patients. We analyzed adult patients (≥18 years) with SLE (n = 7,833) from three departments using a population-based electronic medical record database (2000-2024). Among them, 3,157 (40.3%) patients developed an infection after 72 h of hospitalization. An initial comprehensive variable pool of 108 candidate predictors was included, encompassing demographics, comprehensive laboratory parameters, clinical features, disease activity, and treatment exposures. Ten machine learning models were applied. Model performance was evaluated using six metrics. Model interpretability was achieved using SHapley Additive exPlanations (SHAP). Nine predictors were selected: daily prednisone equivalent dose, albumin, hydroxychloroquine use, C-reactive protein, D-dimer, glucose, cystatin C, hemoglobin, and alpha1-globulin. Among all models tested, the Gradient Boosting model demonstrated the best overall performance on the independent validation set, with an area under the curve (AUC) of 0.858, with its robustness confirmed by 5-fold and 10-fold cross-validation (mean AUCs of 0.855 ± 0.002 and 0.854 ± 0.008, respectively). SHAP analysis revealed that daily prednisone equivalent dose, albumin, and hydroxychloroquine use were the most influential factors. We developed and validated a high-performance, explainable ML model using nine routinely available clinical variables to accurately predict in-hospital infection risk in SLE patients. This tool provides transparent, individualized risk assessment and has the potential to guide personalized clinical stratification and early intervention, ultimately improving patient outcomes.

[This corrects the article DOI: 10.34133/research.0716.].

Mesangial proliferative glomerulonephritis (MsPGN) is a common cause of end-stage renal disease, characterized by mesangial cell proliferation within glomeruli. Mesangial cell activation triggered by inflammation is a key factor in the development of MsPGN. However, effective therapeutic strategies targeting this process are still limited. Here, we uncovered, for the first time, the direct effects of chlorogenic acid (CGA), a naturally occurring small-molecule compound with anti-inflammatory and antiproliferative properties, on mesangial cells in an anti-Thy1 nephritis animal model. A multi-dimensional pharmacological platform integrating laser microdissection-coupled glomerular proteomics affinity deconvolution, surface plasmon resonance, molecular dynamics, and enzyme assays identified Ras-related C3 botulinum toxin substrate 1 (RAC1) as the direct target of CGA. Mechanistically, CGA competitively binds to the LYS15, PRO33, and THR34 amino acid residues—located within residues 57–65 of the GTP/GDP-binding domain of RAC1, inhibiting its activation and subsequently reducing AKT phosphorylation while suppressing Thrombospondin-1 secretion from mesangial cells—a key ligand for macrophage CD36 receptors. This interaction deactivates macrophages and lowers the levels of inflammatory cytokines, including TNFα, IL1β, and IL6. Significantly, as a novel natural RAC1 inhibitor, CGA disrupts mesangial-macrophage crosstalk by dual suppression of regional immunity and cellular proliferation, thus conferring renal protection in MsPGN models. Our findings highlight CGA as a promising pharmacotherapy, offering a mechanism-driven, natural product-based strategy to mitigate MsPGN progression.

BackgroundThe prognosis of IgA nephropathy (IgAN) varies greatly but tends to be poor. The purpose of the present study was to screen for urinary sediment miRNAs that could be used for the non-invasive prediction of IgAN progression and to explore the mechanisms explaining this.MethodsWe studied two independent cohorts (2014–2015 and 2018–2022) to identify urinary sediment miRNAs that could be used to predict IgAN progression. Bioinformatic analysis and dual-luciferase experiments were used to identify target genes for miR-142-3p. The fibrotic phenotype of tubular epithelial cells was evaluated in HK-2 cells.ResultsIn both the training and validation cohorts, the urinary miR-142-3p expression in patients who showed IgAN progression was significantly higher than that in those who did not (P < 0.0001 and P = 0.003, respectively). Multivariate Cox regression analysis showed that high urinary miR-142-3p expression was an independent risk factor for IgAN progression (P < 0.001). Using the International IgA Nephropathy Prediction Tool (IIGANPT) as a reference, we replaced the pathologic indices in the IIGANPT model with the miR-142-3p expression and found that this did not reduce the predictive value of the model (P = 0.228). miR-142-3p is principally expressed in renal tubular epithelial cells, and the in vitro experiments showed that miR-142-3p influences PI3K–AKT pathway activity via inositol polyphosphate-5-phosphatase, thereby playing a role in this cell type’s fibrosis phenotype.ConclusionsUrinary miR-142-3p is a biomarker for the progression of IgAN and is involved in the exacerbation of renal fibrosis. Urinary miR-142-3p can be used to replace pathologic indices in the IIGANPT without reducing its predictive efficacy, implying that this modified tool could be used to non-invasively predict IgAN progression.