紫斑病性腎炎

BACKGROUND: Immunoglobulin A vasculitis nephritis (IgAVN) is the most severe complication of IgA vasculitis (IgAV) in children, yet early predictors of renal involvement remain limited. The aim of this study is to analyse the risk factors for the development of IgAVN in children with IgAV, with a view to improving early diagnosis and treatment, reducing complications and enhancing patient prognosis. METHODS: This was a retrospective analysis. A total of 100 pediatric patients with IgAV hospitalized at Children's Hospital of Fudan University Xiamen Branch (Xiamen Children's Hospital) between January 2023 and June 2025 were included in the study. Patients were divided into two groups based on the presence or absence of IgAVN. Clinical characteristics and laboratory parameters were collected. Risk factors were identified using univariate and multivariate analyses, and a risk prediction model was established using logistic regression. Model performance was evaluated using the area under the receiver operating characteristic (ROC) curve (AUC). RESULTS: A total of 100 children with IgAV were ultimately included in this study, comprising 56 males and 44 females. They were divided into an IgAVN group (n=32) and a non-IgAVN group (n=68). Univariate analysis revealed that three laboratory parameters [C‑reactive protein (CRP), neutrophil‑to‑lymphocyte ratio (NLR), fibrinogen degradation products (FDP)] showed statistically significant differences between the IgAVN and non-IgAVN groups (P<0.05). We included the three laboratory parameters (CRP, NLR, and FDP) that showed statistically significant differences in the univariate analysis into the multivariate analysis and found that elevated NLR [odds ratio: odds ratio (OR) =1.446, 95% confidence interval (CI): 1.080-1.934, P=0.01] and elevated FDP (OR =1.854, 95% CI: 1.133-3.034, P=0.01) were independent risk factors for the development of IgAVN in children with IgAV. ROC curve analysis results showed that the AUCs for NLR >5.23 and FDP >12.35 µg/mL were 0.634 and 0.830, respectively, while the AUC for the combined NLR and FDP model was 0.882. Compared with individual indicators, the combined model demonstrated superior predictive value for IgAVN, with a sensitivity of 86.95% and a specificity of 87.40%. CONCLUSIONS: Elevated NLR and FDP are independent risk factors for the development of IgAVN in patients with IgAV. The combination of NLR >5.23 and FDP >12.35 µg/mL demonstrates good clinical predictive value for IgAVN and warrants attention from clinicians.

OBJECTIVE: IgA vasculitis nephritis (IgAVN) is the principal cause of morbidity and mortality in children with IgA vasculitis (IgAV),the pathogenesis of the renal injury and predictive biomarkers are still unclear. In this study, we performed an integrated untargeted and targeted metabolomics to identify candidate biomarkers and explore oxidative stress-related alterations associated with IgAVN. METHODS: Serum samples were collected from 115 IgAV and 111 IgAVN children. We conducted untargeted metabolomics for preliminary screening of potential biomarkers on 50 IgAV and 50 IgAVN children and then performed validation experiments based on targeted LC-MS/MS on 65 IgAV and 61 IgAVN children. In addition, an IgAVN animal model was established to preliminarily verify oxidative stress-related alterations associated with key metabolic abnormalities by assessing the levels of GSH, GSH/GSSG, MDA, 4-HNE, NRF2, HO-1, and GPX4. RESULTS: A total of 45 differential metabolites were identified between the IgAV and IgAVN groups, including 23 upregulated and 22 downregulated metabolites, which were mainly enriched in glutathione metabolism, pyruvate metabolism, the citrate cycle, sphingolipid metabolism, and steroid hormone biosynthesis. Further targeted validation confirmed that six metabolites, including sphinganine, dehydroepiandrosterone, kynurenine, glutathione, nervonic acid, and creatine differed significantly between the two groups. The combined model based on these six metabolites showed good discriminatory performance, with an AUC of 0.903 and an area under the PRC curve of 0.909. In the animal experiments, the model group exhibited decreased GSH levels, a disrupted GSH/GSSG balance, increased MDA and 4-HNE levels, as well as abnormal expression of NRF2, HO-1, and GPX4. CONCLUSION: Children with IgAVN exhibit a distinct metabolic profile characterized by glutathione depletion, activation of inflammation-related tryptophan metabolism, lipid/membrane remodeling, and disordered energy metabolism. Sphinganine, dehydroepiandrosterone, kynurenine, glutathione, nervonic acid, and creatine may serve as potential biomarkers for IgAVN, and the combined model based on these metabolites showed good discriminatory ability and potential clinical utility. The consistency between the clinical metabolomics findings and the experimental evidence supports supports glutathione-related oxidative stress and the GSH-NRF2/HO-1/GPX4 axis as candidate pathways associated with IgAVN-related renal injury. These findings provide a basis for early risk identification and future mechanistic and pharmacological investigations in pediatric IgAVN.

BACKGROUND: Children with IgA vasculitis (IgAV) may develop nephritis after initially presenting without kidney involvement. We evaluated whether a cytokine augmentation score (CAS) was associated with improved six-month incident nephritis risk stratification beyond clinical variables and routine inflammatory markers. METHODS: This single-center cohort screened children younger than 18 years with IgAV from January 2023 to June 2024 and used standardized six-month renal outcome ascertainment. Children meeting accepted IgAV classification criteria, with no nephritis during the baseline decision window, complete baseline biomarker data, and six-month renal outcome ascertainment formed the cohort. A routine inflammatory index score (RIIS) summarized z-transformed natural-log C-reactive protein-to-albumin ratio (CAR), neutrophil-to-lymphocyte ratio (NLR), and systemic immune-inflammation index (SII); CAS summarized z-transformed natural-log interleukin (IL)-6, tumor necrosis factor alpha (TNF-α), IL-17A, IL-18, and IL-23. Multivariable logistic regression compared a routine clinical plus RIIS model with a cytokine-augmented model; the area under the receiver operating characteristic curve (AUC), Brier score, calibration, bootstrap optimism correction, decision-curve net benefit, and sensitivity analyses were evaluated. RESULTS: Among 447 screened children, 337 were analyzed; 91 (27.0%) developed incident nephritis. CAS was independently associated with nephritis after adjustment for age, sex, symptom-to-blood-draw interval, gastrointestinal involvement, systolic blood-pressure percentile, subthreshold urinary warning signs, and RIIS (adjusted odds ratio per standard deviation (SD), 2.97; 95% confidence interval (CI), 2.01-4.39; p < 0.001). Adding CAS improved the AUC from 0.724 to 0.801 (Δ0.077; 95% CI, 0.035-0.124; p = 0.001), reduced the Brier score from 0.168 to 0.149, and yielded an optimism-corrected AUC of 0.782. CONCLUSIONS: In this single-center derivation cohort, CAS improved internally evaluated discrimination, Brier score, and risk separation beyond clinical variables and RIIS. The model remains investigational pending external validation, assay standardization, and implementation testing.

INTRODUCTION AND AIM: Immune-mediated nephropathies are a mechanistically diverse group of kidney disorders in which dysregulated innate and adaptive immunity drive sustained inflammation, tissue injury, and progressive fibrosis. The kidney is not a passive target of these processes but an active immunological organ, where crosstalk between resident parenchymal cells and infiltrating leukocytes shapes both initiation and progression of disease. Advances in immunogenetics and molecular pathology have allowed several previously idiopathic entities-lupus nephritis, IgA nephropathy, ANCA-associated vasculitis, membranous nephropathy, and complement-mediated glomerulopathies-to be reclassified along mechanism-based lines. This review synthesizes the current understanding of their immunopathology, with emphasis on convergent signaling networks and on translational implications for diagnosis, risk stratification, and targeted therapy. METHODOLOGY: We adopted an evidence-based narrative approach, integrating clinical and experimental findings from immunology, nephrology, immunogenetics, and multi-omics. Key domains examined included immune tolerance, immune-complex biology, complement dysregulation, the renal immune microenvironment, cytokine and chemokine networks, non-coding RNA regulation, and immune-derived renal biomarkers. Comparative analysis was used to distinguish shared immune programs from disease-specific cascades across the major nephritic syndromes. RESULTS AND DISCUSSION: Synthesizing evidence from over 150 peer-reviewed publications (2015-2025) across five major immune-mediated nephropathies, several recurrent immune modules emerge: autoantibody generation, complement activation, macrophage M1/M2 repolarization, and NLRP3 inflammasome priming. These converge on canonical signaling axes (TLR-MyD88, NF-κB, JAK-STAT, cGAS-STING, TGF-β/Smad), linking immune activation to glomerular injury and interstitial fibrosis. Established biomarkers (anti-dsDNA, anti-PLA2R, Gd-IgA1) guide diagnosis and risk stratification, while lncRNA signatures and exosomal cargo represent emerging non-invasive monitoring tools. Mechanism-targeted therapies-B-cell depletion, complement inhibition, and inflammasome modulation-are reshaping the treatment landscape. CONCLUSION: Immune-mediated nephropathies arise from the interaction between systemic immune dysregulation and a nephron-specific immune microenvironment. Distinguishing the shared immune programs from disease-defining cascades provides a rational basis for stratification and precision medicine. Integrated serologic, urinary, histologic, genetic, and multi-omics biomarkers can support earlier diagnosis and dynamic treatment adjustment. Therapy that targets the dominant pathogenic axis in each patient-rather than broad immunosuppression-offers the most realistic route to delaying end-stage renal disease, reducing toxicity, and improving long-term outcomes.

Autoimmune nephrological and rheumatological diseases involve macrophage-driven inflammation, yet disease activity is often assessed using invasive or non-specific measures. Soluble CD163 (sCD163), released from activated monocytes and macrophages, is emerging as a biomarker of macrophage-mediated inflammation in these conditions. This narrative review summarizes current evidence on the diagnostic, prognostic, and disease-monitoring potential of sCD163 measured in blood, urine, and synovial fluid in autoimmune nephrological and rheumatological diseases. This review is based on a narrative analysis of selected publications investigating the clinical utility of sCD163 in autoimmune kidney and rheumatic diseases, with emphasis on correlations with disease activity, histopathological findings, and clinical outcomes. Urinary sCD163 shows excellent diagnostic accuracy for active lupus nephritis (area under the receiver operating characteristic [AUROC] 0.89-0.998), correlates with histological activity index (but not chronicity), and distinguishes ongoing inflammation from chronic damage during treatment. In IgA nephropathy, it predicts remission failure and greater benefit from corticosteroids. In ANCA-associated vasculitis, it identifies active renal involvement (AUROC 0.95 in multicenter cohorts). In rheumatoid arthritis (RA), serum sCD163 correlates with early disease activity, predicts radiographic progression, and detects subclinical macrophage activation in remission. In spondylarthritis, synovial fluid sCD163 reflects a disease-specific M2-polarized macrophage phenotype distinct from RA. Utility is compartmentalized: urinary levels indicate intrarenal macrophage activation, synovial fluid local joint inflammation, and serum systemic activation. sCD163 is a promising macrophage-specific biomarker across autoimmune diseases, but its compartmentalized nature requires context-specific measurement. Before clinical implementation, assay standardization, multicenter validation, and interventional trials showing the benefit of sCD163-guided management are needed.