The clerkship represents the initial stage of medical students' clinical practice, during which clinical reasoning training is emphasized. However, clinical reasoning training during the clerkship encounters several challenges, including limited teaching time and difficulties in adapting to the clinical environment. We developed a three-step clinical reasoning course based on David Kolb's Experiential Learning Cycle model to bridge the learning gaps in the existing clerkship model and then evaluated its impact on performance in clerkship summative evaluations. The three-step clinical reasoning course consists of three parts, including online practice, case-based clinical reasoning lessons, and role-play exercises. During the rotation in the nephrology department, eight student groups (including 50 clerkship students) were assigned to either a control group or a three-step intervention group using a quasi-experimental design. The control group received the conventional clinical reasoning course, while the three-step group received the three-step clinical reasoning course. We evaluated the two groups regarding knowledge, clinical skill, clinical reasoning and satisfaction. The mean score of clinical skills exam for patients’ consultation of three-step group was significantly higher than that of the control group (88.45 ± 8.18 vs 78.13 ± 14.34, P < 0.01). The mean score on clinical reasoning tests was significantly higher in the three-step group than in the control group (24.73 ± 1.96 vs 23.18 ± 1.89, P < 0.01). Student satisfaction of three-step group was notably higher than that in the control group. The three-step course provided clerkship students with a structured, dynamic, and clinically relevant experience, enabling them to enhance their patient consultation skills and clinical reasoning.

Long-term outcomes of kidney allografts vary significantly among deceased donor kidney transplant recipients, and current prediction tools struggle to integrate comprehensive pre- and post-transplant factors. Extended longitudinal follow-up data beyond five years remains particularly scarce in kidney transplantation research despite being crucial for understanding true long-term outcomes. To address this, we developed and validated machine learning models to predict 5-year allograft survival using a distinctive cohort of 940 adult deceased donor kidney transplantation recipients with extended follow-up exceeding 5 years. Two predictive models were developed: a pre-transplant model (Kidney Allograft Prediction of Transplant Outcome Risk, KAPTOR-pre) using pre-transplant donor-recipient matching data, and a 1-year landmark conditional prediction model (KAPTOR-full) incorporating both pre- and post-transplant parameters, pathological data, and laboratory markers from the first year. KAPTOR-full achieved excellent discrimination with area under the receiver operating characteristic of 0.904, while KAPTOR-pre performed well at 0.813. In internal validation, both models showed higher C-index and improved risk stratification compared with established prognostic tools including KDPI. The extended follow-up period allowed internal assessment of model performance for 5-year outcomes. Ultimately, our models integrating routine clinical variables demonstrated excellent predictive performance for long-term graft survival. While the pre-transplant model achieved good discrimination, the addition of first-year post-transplant data significantly enhanced predictive accuracy. Both models outperformed existing tools in internal validation and may support personalized risk assessment, pending independent multicenter validation.

Objective This study aims to characterize pathogenic somatic mutations in patients with autoinflammatory or autoimmune diseases lacking disease-causing germline mutations, explore their contribution to disease pathogenesis and progression, and evaluate their implications for diagnosis and targeted therapy.Methods We performed a systematic analysis of somatic mutations in a selected panel of 185 immune-related genes in 2,912 patients with autoinflammatory or autoimmune diseases, recruited from 41 medical centers across China, who were previously negative for germline mutations based on whole-exome sequencing.Results We identified both previously reported and novel somatic mutations in genes such as UBA1, KRAS, and NLRP3. Pathogenic somatic mutations in TNFAIP3 were discovered first in patients with autoinflammatory diseases. The pathogenic somatic mutation detection rate was 1.35% in adults and 0.97% in children, emphasizing the importance of genetic diagnosis and novel gene discovery for somatic mutations. In addition, somatic mutations in Ras-related genes were identified in seven patients, and 39 clonal hematopoiesis-associated mutations were identified in 36 adult patients. Moreover, myeloid cells harboring somatic mutations expanded during disease flare and reduced during remission. Disregarding the dynamic elevation of the variant allele fraction during disease progression led to therapeutic failure.Conclusion This study delineated the genetic landscape of pathogenic somatic mutations underlying autoinflammatory and autoimmune diseases, offering valuable insights for genetic diagnosis and targeted therapies.

Objective To investigate the efficacy and safety of glucocorticoids combined with cyclophos-phamide(CTX)and rituximab(RTX)in elderly patients with anti-neutrophil cytoplasmic antibody(ANCA)-associated vasculitis with renal involvement.Methods Elderly patients(age≥60 years)with ANCA-associ-ated vasculitis and renal involvement admitted to the First Affiliated Hospital,Zhejiang University School of Medicine from December 2019 to November 2022 were retrospectively enrolled.Based on different induction treatment regimens,patients were divided into a control group(glucocorticoids+CTX)and a combination ther-apy group(glucocorticoids+CTX+RTX).Differences in disease remission,end stage renal disease(ESRD),mortality,relapse,and incidence of adverse events were compared between the two groups.Results A total of 60 elderly patients with ANCA-associated vasculitis and renal involvement were ultimately included,with a median follow-up of 29.7(17.2,38.7)months.The control group comprised 26 patients,with a median follow-up of 35.0(28.1,40.3)months;the combination therapy group comprised 34 patients,with a median follow-up of 26.2(16.1,35.1)months.The remission rate at 3 months(64.7%vs.34.6%,P=0.021)and 6 months(76.5%vs.50.0%,P=0.033)of treatment were significantly higher in the com-bination therapy group compared to the control group.No statistically significant differences were found between the two groups in remission rates at 12 months(85.3%vs.65.4%,P=0.071),and last follow-up(76.5%vs.65.4%,P=0.345),nor in the incidence of ESRD(26.5%vs.30.8%,P=0.714),mortality(23.5%vs.26.9%,P=0.764),and relapse(14.7%vs.23.1%,P=0.507)during follow-up.Regarding medication dosage,the cumulative RTX dose in the combination therapy group at 6 months and last follow-up was 0.6(0.4,1.2)g and 0.8(0.5,1.2)g,respectively.The maintenance dose of glucocorticoids(calculated as prednisone dose)[at 6 months:(2.4±1.1)g vs.(4.3±0.8)g,P＜0.001;at last follow-up:3.5(2.1,4.3)g vs.6.5(5.0,7.7)g,P＜0.001],cumulative glucocorticoid dose(methylprednisolone pulse therapy dose converted to equivalent prednisone dose)[at 6 months:(3.7±1.4)g vs.(5.3±0.9)g,P＜0.001;at last follow-up:4.1(3.2,6.2)g vs.7.1(6.2,8.9)g,P＜0.001],and cumulative CTX dose[at 6 months:3.3(1.1,6.2)g vs.5.2(4.5,6.0)g,P＜0.001;at last follow-up:3.6(0.9,6.2)g vs.6.0(5.5,6.8)g,P=0.001]were significantly lower in the combination therapy group than in the control group.Furthermore,the proportion of patients successfully tapering prednisone to≤15 mg/day by week 8 of treatment(76.5%vs.19.2%,P＜0.001)and the proportion completely discontinuing prednisone by 6 months of treatment(44.1%vs.3.8%,P＜0.001)were significantly higher in the combination therapy group.In terms of safety,the incidence of new-onset hyperlipidemia at 6 months(14.7%vs.42.3%,P=0.017)and last follow-up(29.4%vs.73.1%,P=0.013),and the incidence of new-onset hyperglycemia at last follow-up(17.6%vs.50.0%,P=0.008)were significantly lower in the combination therapy group.No significant differences were observed in the incidence of severe infections,malignancies,or cardiovascular and cerebrovas-cular events between the two groups(all P＞0.05).Conclusions For elderly patients with ANCA-associated vasculitis and renal involvement,the regimen of glucocorticoids combined with CTX and individualized RTX demonstrates potential advantages in early remission rate,glucocorticoid tapering,and control of cumulative CTX dose,without increasing the risk of serious adverse events.This regimen may represent an alternative treat-ment option for this patient population;however,its long-term efficacy and safety require further validation through prospective randomized controlled trials.

Introduction:This study explores the potential of estimated glomerular filtration rate (eGFR) slope as a noninvasive marker for predicting renal survival and patient survival in myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody-associated glomerulonephritis (AAGN). Methods:A total of 377 MPO-AAGN patients were included. Kaplan-Meier and Cox regression analyses were performed to assess the predictive value of eGFR slopes for renal survival and patient survival. Then, the models were validated by discrimination, calibration, and decision curve analysis. Results:The eGFR slope (calculated using a linear mixed-effects model with baseline and follow-up eGFR values up to defined timepoints), higher with better renal recovery, had a median of 2.54 (IQR: 0.49-6.02) mL/min/1.73 m2/month for 3 months and 1.90 (IQR: -0.07-4.76) mL/min/1.73 m2/month for 1 year. Multivariate Cox regression identified baseline eGFR (HR = 0.96, 95% CI 0.95-0.98, p < 0.001) and the 3-month eGFR slope (HR = 0.79, 95% CI 0.75-0.85, p < 0.001) as independent protective factors for kidney failure. The model incorporating baseline eGFR and the 3-month eGFR slope outperformed existing risk scores for predicting renal survival. The prediction value of the eGFR slope for patient survival was also found. Both a 3-month eGFR slope >1 mL/min/1.73 m2/month (HR = 0.47, 95% CI 0.31-0.70, p < 0.001) and a 1-year eGFR slope >1 mL/min/1.73 m2/month (HR = 0.42, 95% CI 0.28-0.63, p < 0.001) were independent protective factors for patient survival. The prediction model with a 1-year eGFR slope showed a prediction ability similar to that of the classical model with kidney failure events. Conclusion:eGFR slopes are valuable predictors of renal and patients' survival in MPO-AAGN, providing valuable prognostic information that could enhance risk stratification and clinical decision-making.

BACKGROUND:T lymphocytes play a crucial role in the development of hypertension and associated end-organ damage. CD38 is a well-established surface marker for T-cell activation. However, clinical evidence linking CD38+ T cells, or other specific T-cell subsets, with blood pressure (BP) changes remains limited. We therefore sought to determine whether CD38+ T-cell abundance correlates with BP and whether anti-CD38 therapy influences BP in humans and mice. METHODS:We performed correlation analyses between peripheral immune cell counts and BP in 197 normotensive and 53 hypertensive subjects. The impact of CD38-targeted therapy on BP was evaluated in multiple myeloma patients (control, n=50; daratumumab, n=27). In addition, we used a murine model of angiotensin II-induced hypertension to characterize T-cell frequency and phenotype in the circulation and kidney by flow cytometry. RESULTS:Circulating CD38+ T-cell abundance was inversely correlated with BP in both normotensive and hypertensive subjects. This finding was recapitulated in hypertensive mice, which also showed concomitant accumulation of CD38+ T cells in the kidney. In patients, daratumumab-induced depletion of CD38+ cells reduced systolic BP by ≈10 mm Hg for 4 to 6 weeks. This BP-lowering effect was similarly observed in hypertensive mice given an antimurine CD38 antibody. CONCLUSIONS:Our data identify circulating CD38+ T cells as a novel immunologic biomarker that inversely correlates with BP, potentially reflecting T-cell transmigration during BP elevation.

BACKGROUND:Emerging evidence highlights the critical role of ferroptosis in the pathophysiology of both acute kidney injury (AKI) and chronic kidney disease (CKD). Nuclear factor erythroid 2-related factor 2 (Nrf2), which is activated through pathways involving Takeda G protein-coupled receptor 5 (TGR5), has emerged as a potential therapeutic target to inhibit ferroptosis. METHODS:We evaluated kidney TGR5 expression and urinary TGR5 excretion in AKI patients, as well as in vivo (mouse) and in vitro (cellular) models of AKI induced by ischemia-reperfusion (IR) injury and subsequent CKD. Correlation analyses were conducted with renal function markers. Cellular injury models were established using human renal proximal tubular epithelial cells (HK-2) and human umbilical vein endothelial cells (HUVECs). The TGR5 agonist INT-777 was used to activate TGR5 signaling. Morphological changes in kidney tissues and cells were examined by transmission electron microscopy, and intracellular ferrous iron (Fe2+) levels, reactive oxygen species (ROS), and malondialdehyde (MDA) were quantified with commercial assay kits. RESULTS:Decreased kidney TGR5 expression and increased urinary TGR5 excretion were observed in AKI patients and experimental models, both correlating significantly with impaired renal function. Importantly, treatment with the TGR5 agonist INT-777 activated the TGR5/cAMP/PKA/Nrf2 pathway, suppressed oxidative stress and ferroptosis, and thereby attenuated synchronous injury in tubular epithelial and endothelial cells. CONCLUSIONS:This study offers novel insights into ferroptosis mechanisms in AKI and subsequent CKD, identifying TGR5 as a promising therapeutic target.

Background: Predicting early progression of diabetic kidney disease (DKD) remains challenging. The neutrophil-derived peptide LL37 is implicated in kidney inflammation, yet its role and prognostic value in DKD remains unclear. Methods: RNA sequencing dataset was analyzed to examine the expression of CAMP (encoding LL37) and myeloperoxidase (MPO) in peripheral blood from diabetic mellitus patients. A clinical cohort of 94 biopsy-proven DKD patients and 63 healthy controls (HC) was established. Serum LL37 and MPO-DNA complexes were measured using enzyme-linked immunosorbent assay. The correlation between serum LL37 and MPO-DNA complex levels and kidney function was assessed, and assessed their association with DKD progression using restricted cubic spline analysis and Cox proportional hazards regression models. Results: Bioinformatics analysis revealed significantly elevated CAMP expression in DM patients, with strong neutrophil infiltration. In the clinical cohort, serum LL37 levels were significantly higher in DKD patients than in HC, showing discriminatory power for DKD diagnosis (AUC=0.90, 95%CI: 0.85-0.96). Serum LL37 and MPO-DNA complex levels correlate with elevated serum creatinine and reduced eGFR. After a median follow-up of 39 months, 60 patients (63.83%) experienced renal progression events. After adjusting for confounding factors, elevated serum LL37 and MPO-DNA complex levels were independent risk factors for DKD progression [per Ln-transformed HRs: 2.290 (95% CI: 1.491-3.518) and 1.833 (95% CI: 1.261-2.664), respectively]. Conclusion: Elevated serum LL37 and MPO-DNA complex levels are independently associated with kidney disease progression in patients with DKD, and increased circulating LL37 may be closely linked to neutrophil activation.

Post-transplant dyslipidemia is frequently observed and has been associated with graft survival. Traditional lipid parameters show inconsistent associations with graft outcomes, whereas remnant cholesterol (RC) may provide additional prognostic value; however, its role remains unclear in kidney transplant recipients. In this retrospective cohort of 1,943 living donor kidney transplant recipients, a 365-day landmark design was applied. Lipid exposure was defined as mean levels within the first year after transplantation, including RC, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, total cholesterol (TC), and triglycerides (TG). Multivariable Cox proportional hazards models were used to estimate adjusted hazard ratios, and restricted cubic spline analyses were used to explore potential dose–response patterns. Lipid parameters were additionally analyzed as categorical variables. Subgroup analyses assessed potential effect modification, and incremental value analyses evaluated model improvement. Elevated RC (HR 2.38, 95

Kidney disorders, including acute kidney injury (AKI), chronic kidney disease (CKD), diabetic nephropathy (DN), and clear cell renal cell carcinoma (ccRCC), represent major causes of morbidity and mortality worldwide and remain significant challenges in clinical management because of their complex pathogenesis and limited therapeutic options. Recent advances in epitranscriptomics have highlighted RNA methylation as an important post-transcriptional regulatory mechanism involved in renal physiology and disease development. Diverse RNA modifications, including N6-methyladenosine (m6A), 5-methylcytosine (m5C), N1-methyladenosine (m1A), N7-methylguanosine (m7G), and 3-methylcytidine (m3C), dynamically regulate RNA metabolism by affecting transcript stability, translation, splicing, and degradation. Increasing evidence demonstrates that RNA methylation regulators, including methyltransferases such as METTL3 and METTL14, demethylases such as FTO and ALKBH5, and reader proteins such as YTH domain-containing family members, participate in multiple pathogenic processes, including inflammation, fibrosis, oxidative stress, metabolic dysregulation, and tumor progression in renal disorders. Aberrant expression of these regulators has been closely associated with disease severity and progression. In this review, we summarize current knowledge regarding major RNA methylation modifications and their regulatory machinery in a spectrum of kidney diseases, with particular emphasis on the molecular mechanisms through which RNA methylation influences renal injury and repair. We further discuss the emerging value of RNA methylation-related molecules as potential biomarkers and therapeutic targets, aiming to provide new insights into epitranscriptomic regulation in kidney disease and its translational potential.

BACKGROUND:Macrophages are critical in antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (AAGN). This study investigated macrophage-associated genes (MAGs) ZFP36 and CEBPA in AAGN renal tissue and evaluated their role in glomerular endothelial injury. METHODS:Macrophage infiltration and its association with prognosis were assessed in renal tissues via immunohistochemistry. ZFP36 and CEBPA were identified via the Gene Expression Omnibus (GEO) database. Their expression in AAGN and correlation with immune cell infiltration and clinical indicators were analyzed. Serum from healthy individuals and AAGN patients was used to stimulate human renal glomerular endothelial cells (HRGECs), and ZFP36 and CEBPA expression was measured using western blotting and real-time PCR. Functional studies included gene knockdown and overexpression, actinomycin D chase assays, NF-κB inhibition, and a direct co-culture system with THP-1-derived macrophages. RESULTS:AAGN renal tissues showed marked immune infiltration and macrophage activation, predicting poor prognosis. ZFP36 was downregulated and low ZFP36 expression correlated with poor prognosis, while CEBPA was upregulated and high CEBPA expression correlated with poor prognosis. Immunofluorescence demonstrated partial localization of both proteins in CD31-positive glomerular endothelial areas. In HRGECs, ZFP36 attenuated inflammatory responses, accelerated TNF-α and IL6 mRNA decay, and was associated with reduced NF-κB activation, whereas CEBPA promoted endothelial inflammatory mediator expression. In co-culture experiments, endothelial ZFP36 reduced, whereas endothelial CEBPA increased, TNF-α production in adjacent macrophages. CONCLUSIONS:ZFP36 and CEBPA are macrophage-associated genes linked to immune infiltration, renal prognosis, and endothelial inflammatory responses in AAGN, and may serve as potential tissue biomarkers and therapeutic targets.

Daratumumab (Dara)-based regimens have demonstrated efficacy in AL amyloidosis. However, real-world treatment strategies may differ from the standard Dara-CyBorD regimen because of variations in drug availability and clinical practice. This study compared intravenous daratumumab-based regimens with cyclophosphamide-bortezomib-dexamethasone (CyBorD) in patients with kidney involvement. Patients initially treated with intravenous daratumumab-based regimens or CyBorD were retrospectively included. Treatment efficacy, safety and factors associated with treatment response were analyzed. Ninety-three patients were included, with 30 patients in the Daratumumab group and 63 patients in the CyBorD group. After a median follow-up of 29.8 months in the Daratumumab group and 32.4 months in the CyBorD group, the proportion of patients achieving hematologic very good partial response or better was 83.3

Background:Predicting early progression of diabetic kidney disease (DKD) remains challenging. The neutrophil-derived peptide LL37 is implicated in kidney inflammation, yet its role and prognostic value in DKD remain unclear. Methods:RNA sequencing dataset was analyzed to examine the expression of CAMP (encoding LL37) and myeloperoxidase (MPO) in peripheral blood from diabetic mellitus patients. A clinical cohort of 94 biopsy-proven DKD patients and 63 healthy controls (HCs) was established. Serum LL37 and MPO-DNA complexes were measured using enzyme-linked immunosorbent assay. The correlation between serum LL37 and MPO-DNA complex levels and kidney function was assessed and assessed their association with DKD progression using restricted cubic spline analysis and Cox proportional hazards regression models. Results:Bioinformatics analysis revealed significantly elevated CAMP expression in DM patients, with strong neutrophil infiltration. In the clinical cohort, serum LL37 levels were significantly higher in DKD patients than in HC, showing discriminatory power for DKD diagnosis (AUC = 0.90, 95% CI: 0.85-0.96). Serum LL37 and MPO-DNA complex levels correlate with elevated serum creatinine and reduced eGFR. After a median follow-up of 39 months, 60 patients (63.83%) experienced renal progression events. After adjusting for confounding factors, elevated serum LL37 and MPO-DNA complex levels were independent risk factors for DKD progression (per Ln-transformed HRs: 2.290 [95% CI: 1.491-3.518] and 1.833 [95% CI: 1.261-2.664], respectively). Conclusion:Elevated serum LL37 and MPO-DNA complex levels are independently associated with kidney disease progression in patients with DKD, and increased circulating LL37 may be closely linked to neutrophil activation.

To our knowledge, no large‑sample epidemiological studies on chronic kidney disease‑associated pruritus (CKD‑aP) have been reported in China in recent years. We aimed to investigate the prevalence and related factors of CKD-aP in Chinese dialysis population. This study included data on 9,589 dialysis patients across 30 provincial-level administrative divisions in mainland China between May 2022 and December 2022. The EQ-5D was used to collect patient information. Pruritus severity was assessed using the Numerical Rating Scale (NRS). Generalized estimating equations (GEE) were used to explore the potential influencing factors of CKD-aP. The prevalence of CKD-aP in Chinese adult dialysis patients was 60.3%. The prevalence of mild, moderate, and severe pruritus was 44.4%, 12.5%, and 3.3%, respectively. The prevalence of pruritus, moderate-to-severe pruritus, and severe pruritus in hemodialysis (HD) patients was 59.9%, 16.0%, and 3.4%, respectively. The prevalence of pruritus, moderate-to-severe pruritus, and severe pruritus in peritoneal dialysis (PD) patients was 61.8%, 14.1%, and 2.8%, respectively. No significant difference in pruritus prevalence was observed between HD (59.9%) and PD (61.8%) patients. Only 2.9% of the patients received potentially effective treatment (gabapentinoids 2.8%, kappa opioid receptor agonists 0.1%). Smoking history, diabetic nephropathy, cardiovascular diseases, dialysis vintage, eosinophil count, serum total calcium, and serum phosphorus were factors associated with CKD-aP. CKD-aP is highly prevalent among Chinese dialysis patients, with comparable rates between HD and PD populations. Several modifiable and non-modifiable factors were significantly associated with pruritus. Few patients received potentially effective treatment. These results highlight the potential targets for improving patient management.

Background:The efficacy of non-peptide small-molecule glucagon-like peptide-1 (GLP-1) receptor agonists in diabetic kidney disease remains uncertain, particularly as add-on therapy to contemporary high-intensity treatments. We assessed HRS-7535, a novel oral small-molecule GLP-1 receptor agonist, in this population. Methods:SOLID-DKD was a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial conducted at 72 clinical sites in China. Adults with diabetic kidney disease (urinary albumin-to-creatinine ratio [UACR] 300-<3000 mg/g; estimated glomerular filtration rate [eGFR] ≥30 mL/min per 1.73 m2) were randomly assigned (1:1:1) via a central interactive web-response system, stratified by baseline UACR, concomitant SGLT2 inhibitor use, and finerenone use to once-daily oral HRS-7535 (30 mg or 90 mg) or placebo for 16 weeks. The primary endpoint was the relative change in UACR from baseline to week 16. This trial is registered at ClinicalTrials.gov (NCT06415214) and is completed. Findings:Between June 21, 2024, and March 30, 2025, 281 participants were randomised; 280 received at least one dose (30 mg: n = 93; 90 mg: n = 94; placebo: n = 93). Baseline median UACR was 763 mg/g; 181 (64.6%) participants were receiving SGLT2 inhibitors and 68 (24.3%) were receiving finerenone. At week 16, the placebo-corrected reduction in UACR with 90 mg was -32% (95% CI -43 to -18; treatment-policy estimand [intention-to-treat]) and -38% (-49 to -24; efficacy estimand [on-treatment analysis]); with 30 mg, -14% (-29 to 4) and -19% (-34 to -2), respectively. Compared with placebo, the mean difference in glycated haemoglobin with HRS-7535 90 mg was -1.09% (-1.32 to -0.86) and in body weight was -2.95% (-3.94 to -1.95). Adverse events were primarily mild-to-moderate gastrointestinal events during dose escalation. Serious adverse events occurred in 5 (5.4%), 4 (4.3%), and 2 (2.2%) participants in the 30 mg, 90 mg, and placebo groups. Discontinuation due to adverse events occurred in 3 (3.2%), 1 (1.1%), and 0 participants, respectively. No deaths occurred. Interpretation:HRS-7535 dose-dependently reduced albuminuria in patients with diabetic kidney disease receiving intensive contemporary therapy, with a short-term safety profile consistent with the GLP-1 receptor agonist class, supporting its evaluation in phase 3 renal outcome trials. Funding:Jiangsu Hengrui Pharmaceuticals.

Growing evidence suggests that the gut-kidney axis may contribute to the pathogenesis of IgA nephropathy (IgAN). However, the effects of immunosuppressants on the intestinal microbiome remain unclear. We investigated how different therapeutic strategies influence gut microbial composition in IgAN patients. We enrolled 46 patients with IgAN and 37 healthy controls (HC). Patients were stratified by treatment regimen into a supportive care group or an immunosuppressive therapy group, with subgroups defined by the use of leflunomide and systemic glucocorticoids. Fecal samples from patients in clinical remission were analyzed and 16S rRNA gene sequencing was performed. We examined microbial α- and β-diversity, taxonomic differences, and predicted functional pathways using Linear Discriminant Analysis Effect Size and Kyoto Encyclopedia of Genes and Genomes (KEGG)-based annotation. Compared with HCs, IgAN patients showed significantly reduced microbial α-diversity, depletion of beneficial taxa such as Faecalibacterium, and enrichment of potential pathogens, including Enterobacteriaceae. Neither supportive care and systemic glucocorticoid therapy were not associated with an apparent restoration of overall microbial diversity or community structure. Conversely, leflunomide treatment was associated with higher microbial diversity and a taxonomic profile that showed a trend toward similarity with healthy controls. Notably, anti-inflammatory bacteria, including Dysosmobacter welbionis, Ruthenibacterium lactatiformans, and Intestinimonas butyriciproducens were significantly enriched (all p < 0.01). KEGG-based predictions revealed downregulation of pro-inflammatory pathways, accompanied by reduced levels of inflammatory markers (p < 0.05). Overall, the therapeutic efficacy of leflunomide in IgA nephropathy is associated with specific characteristics of the patients' gut microbiota, which may be linked to its potential to reverse dysbiosis and enhance anti-inflammatory effects.

This study aimed to analyze the risk factors for segmental ossification volume progression in cervical ossification of the posterior longitudinal ligament (OPLL) after laminoplasty (LP). Patients with OPLL who underwent LP at our institution and were followed for more than 12 months were enrolled. Three-dimensional models were reconstructed using CT images to measure the OPLL volume preoperatively and at final follow-up, and the ossification volume of each segment was calculated. The annual volume growth rate (AVGR) of OPLL was calculated by dividing the volume change by the follow-up duration. OPLL segmental ossification volume with an AVGR greater than 12.24