Vamifeport, a clinical stage oral ferroportin inhibitor, alleviates murine lupus nephritis: A pilot study.

Clinicopathological landscape of lupus nephritis in Northeast China: A retrospective cohort study of determinants for moderate-to-severe renal dysfunction.

Extracellular vesicles and their role in Lupus Nephritis: A scoping review.

Chronic kidney disease trajectories in lupus nephritis: Is progression unavoidable?

Triple Therapy With Calcineurin Inhibition Enhances Remission in Childhood-Onset Lupus Nephritis.

New developments and future directions in the management of systemic lupus erythematosus.

Immunologic links between cutaneous lupus and internal organ involvement in SLE: A systematic review and meta-analysis.

Lupus nephritis (LN) represents one of the most severe manifestations of childhood systemic lupus erythematosus (cSLE), often progressing rapidly and resulting in renal impairment or even end-stage renal disease. Early diagnosis and precise assessment of disease activity are essential for guiding therapy and improving clinical outcomes. However, conventional serological and urinary biomarkers exhibit limited sensitivity and specificity, while renal biopsy, although the diagnostic gold standard, is invasive and unsuitable for longitudinal monitoring. Surface-enhanced Raman spectroscopy (SERS), a noninvasive analytical approach, offers substantial potential for detecting the molecular characteristics of LNs. In this study, a high-throughput SERS microspot array plate platform was established to perform dual-modal serum and urine SERS metabolic fingerprint analyses in healthy controls (n = 40), systemic lupus erythematosus (n = 40), and LN patients (n = 60). The dual-modal fusion model demonstrated superior performance over single-modal models in both LN diagnosis and disease activity assessment, achieving notably enhanced sensitivity, specificity, and overall accuracy. Furthermore, dual-modal SERS profiling revealed key biomolecular alterations associated with immune activation, inflammatory responses, and renal injury in children, providing molecular-level insights into the pathophysiological mechanisms underlying cSLE and LN.

In South Korea, belimumab is indicated for patients with systemic lupus erythematosus (SLE), including paediatric patients aged ≥ 5 years, and for adults with lupus nephritis, based on clinical trial evidence; however, real-world data in this population remain limited. To assess the real-world safety and effectiveness of intravenous (IV) belimumab administered in patients with SLE in South Korea. This observational study (GSK Study 216984) enrolled patients with active SLE and patients with lupus nephritis across 18 South Korean institutions (July 2021-February 2023). Patients received on-label IV belimumab plus standard therapy (antimalarials, glucocorticoids and immunosuppressants). Data were collected for a minimum of 48 weeks as part of routine clinical practice (July 2021-March 2024). Safety was assessed by monitoring the incidence of adverse events (AEs), adverse drug reactions (ADRs), serious AEs (SAEs)/ADRs and AEs of special interest (including psychiatric events) and summarised descriptively. Changes in SELENA-SLEDAI scores, laboratory biomarkers and glucocorticoid dosage from baseline to week 24 or 48 were tested using the Wilcoxonsigned-rank test. Of 126 enrolled patients, 105 were eligible for the ≥ 48-week safety evaluation (completed ≥ 24 weeks of belimumab treatment). Patients were mostly female (91.4%, n = 96/105), with mean (SD) SLE duration of 9.9 (8.1) years; 45.7% (n = 48/105) of patients had lupus nephritis. AEs and SAEs were experienced by 66.7% (n = 70/105) and 18.1% (n = 19/105) of patients; most events were mild or moderate in severity and unlikelyto be related to belimumab. ADRs were reported for 3.8% (n = 4/105) of patients, and psychiatric events for 2.9% (n = 3/105). SELENA-SLEDAI and laboratory biomarkers significantly improved, and glucocorticoid dosage significantly reduced, between baseline and weeks 24 and 48. This real-world study identified no new safety concerns and demonstrated effectiveness of belimumab, supporting its use in Korean patients.

Lupus nephritis (LN) is a common complication of systemic lupus erythematosus (SLE) that symbolizes a primary contributor of morbidity and mortality. Dihydroartemisinin (DHA; artenimol) shows good therapeutic effects on LN. Its pharmacological target remains unclear. Proteolysis targeting chimeras (PROTAC) technology was used to identify the targets of DHA in LN treatment. The activity of a novel compound termed A1 was assessed through cytotoxicity and anti-inflammatory assays in vitro. The target of DHA was screened by the A1 integrating with proteomics and then validated via western blotting, co-immunoprecipitation (Co-IP), immunofluorescence, molecular docking, cellular thermal shift assay (CETSA) and drug affinity responsive target stability (DARTS) in vitro. Twenty-four-hour proteinuria, inflammatory cytokines, serum biochemical indicators, immune complex deposition and renal pathological injury were detected. Adeno-associated virus-mediated RNA interference in silencing CARD6 was conducted in vivo to comprehensively evaluate the effect and the target of DHA on MRL/lpr mice. CARD6 was the most notably degraded protein affected by A1 that identified as the target of DHA. Specifically, DHA interacted with CORE-CARD6 at the 481-949aa region. DHA blocked CARD6 to inhibit RIP2/NF-κB pathway, which manifested anti-inflammatory properties in vivo and in vitro. Silencing CARD6 ameliorated the inflammatory response of MRL/lpr mice. Notably, the inhibition effects of DHA on the MRL/lpr mice were abrogated when CARD6 was depleted. CARD6 was a therapeutic target of DHA for LN management. This finding highlights the great potential of using PROTAC technology to effectively identify therapeutic targets of natural products.

Lupus nephritis (LN) is a severe manifestation of pediatric systemic lupus erythematosus (pSLE). This study aims to describe the epidemiology, clinical, biological, histological features and prognosis of pediatric LN in the Afro-descendant (AD) population of the French Overseas Departments of America. We conducted a retrospective and longitudinal multicenter study of pediatric LN patients from January 2000 to June 2024. Patients were identified from multiple sources including pediatricians' registries, pathologist's registries for kidney biopsies, national registry for rare diseases and referral centers. Data were collected from medical records. Diagnostic criteria for pSLE kidney impairment were based on international classifications. Twenty-seven patients with pediatric LN were included. The mean age at diagnosis was 11.3 years (range: 6-17) and mean follow-up duration was 7.5 years (range: 0.3-27). Kidney involvement (75% of ISN/RPS class III/IV) was present at pSLE diagnosis in 55% of patients. Kidney flares occurred more frequently in patients under 12 years of age at diagnosis, with an average of 1.7 flares per patient (p = 0.03). The mean number of background therapy per patient during follow up was 2.5 (1-5) with a majority (n = 15, 55%) receiving glucocorticoids and mycophenolate mofetil as first line. Six patients (22%) had an eGFR below 60ml/min/1.73m2 at the last follow-up (2 patients on dialysis, 2 had kidney transplants). This study represents the largest cohort of pediatric LN in AD population. Younger patients exhibited more frequent kidney flares, particularly within the first two years of diagnosis. Overall outcomes in pediatric LN showed a higher rate of dialysis and kidney failure than in Caucasian series. Not applicable.

The diagnosis of kidney disease can be challenging during pregnancy. A kidney biopsy (KB) may be proposed, but there is little recent data available to assess the risk/benefit ratio of this procedure during pregnancy. In this French nationwide survey, we analysed the indications, complications, histological diagnoses, treatments, and obstetric outcomes of pregnant women who underwent native KB between 2006 and 2025. We gathered the medical records of 76 patients, with a median age of 29.5 [range 18-42] years, including 2 with twin pregnancies. KB was performed at a median gestational age of 13.5 [range 4-26] weeks. The main indications for KB were: nephrotic syndrome without AKI (40.8%) and non-nephrotic proteinuria without AKI (40.8%). KB led to a diagnosis in 72 (94.7%) patients. The main histological diagnoses were lupus nephritis (43%), focal segmental glomerulosclerosis (13%), membranous nephropathy (13%), IgA nephropathy (12%), and idiopathic nephrotic syndrome consistent with minimal change disease (5%). One patient experienced bleeding requiring transfusion. Specific treatment was initiated in 48 (63.2%) patients after KB: corticosteroids (35.5%), hydroxychloroquine (27.6%), azathioprine (18.4%), calcineurin inhibitor (13.2%), rituximab (2.6%) and belimumab (1.3%). There was a high incidence of preeclampsia (16.4%), small for gestational age (21.3%) and intrauterine fetal death (9.0%) in this cohort. Preterm birth and low birth weight occurred in 65.0% and 56.7% of cases, respectively. When considered necessary to establish a diagnosis during pregnancy, kidney biopsy performed in the first two trimesters appears to be safe, with a high diagnostic yield and a significant impact on therapeutic decision-making and patient management.

Double-negative T cells in systemic lupus erythematosus: From immunopathology to therapeutic target.

Cytokine Release Syndrome and Cardiogenic Shock Following Anti-Thymocyte Globulin Induction in a Kidney Transplant Recipient: A Case Report.

Mycophenolate mofetil (MMF) is widely used in lupus nephritis (LN), but interindividual variability in pharmacokinetics and pharmacogenetics may affect treatment response. This study investigated the relationship between MMF pharmacokinetics, key genetic polymorphisms, and therapeutic response in Egyptian female LN patients. In this prospective study, 53 female patients with active LN (ISN/RPS class III-IV) maintained on 2g/day MMF were enrolled at the Urology and Nephrology Center, Mansoura University, Egypt. Baseline clinical, laboratory, and histopathological data were collected. Serial blood samples were obtained over 8h for mycophenolic acid (MPA) quantification by LC/MS. Genomic DNA was extracted for UGT2B7 (rs7438135) and SLCO1B1 (rs183624077) genotyping using TaqMan real-time PCR assays. Treatment response was classified as complete or partial remission versus non-response at 6 months. Population pharmacokinetics were analyzed using Monolix 2020R1. Considerable variability in MPA exposure was observed (mean AUC₀-₈: 22.4 ± 12.9µg·h/mL; mean Cmax: 12.9 ± 5.5µg/mL). Responders exhibited higher median AUC₀-₈ than non-responders (23.1 vs. 16.2µg·h/mL; p = 0.039). SLCO1B1 and UGT2B7 genotypes did not differ significantly between responders and non-responders, though TT carriers showed lower MPA AUC₀-₈. Multivariate analysis identified biopsy class (III vs. IV), induction therapy with MMF, and higher MPA AUC₀-₈ as independent predictors of response. MMF exposure, biopsy class, and induction regimen significantly influence therapeutic response in LN. Pharmacokinetic monitoring of MPA may help optimize MMF therapy, while common UGT2B7 and SLCO1B1 variants showed limited predictive value in this cohort.

This study aims to investigate the spatial transcriptomics of hypoxia and immune-mediated damage within renal tissue in patients with lupus nephritis (LN) in comparison to healthy controls from kidney transplants. Renal biopsies from LN patients and transplant controls were imaged using multiplexed cyclic immunofluorescence to spatially quantify immune and endothelial cell markers. An independent LN cohort of patients underwent Visium spatial transcriptomics analysis. Hypoxia was modeled in cell lines and primary neutrophils using cobalt chloride, while urinary neutrophil cargo proteins were measured using ELISA. LN glomeruli exhibited increased HIF1α expressing CD68+ve macrophages and CD66+ve neutrophils along with diffuse perinuclear staining for myeloperoxidase (MPO), indicative of heightened NETosis and N2 reparative neutrophil presence. Spatial transcriptomic analysis confirmed the correlation between glomerular hypoxia and NET formation. The renal pathology Activity Index (AI) was highly correlated with hypoxic neutrophil count, and these parameters correlated with glomerular endothelial rarefaction, and reduced capillary lengths, junctions, and branching. Urinary neutrophil cargo and NET proteins (MPO and proteinase 3) were also elevated in active LN. We posit that glomerular endothelial cell damage leads to hypoxia in LN, resulting in hypoxic, reparative myeloid cells and neutrophil NETosis, while the latter has been linked to downstream inflammation and in situ trapping of anti-nuclear antibodies in LN. These glomerular events underpin high renal pathology activity, and may pave the path towards irreversible damage in LN. Detection of neutrophil cargo in urine supports the potential for a liquid biopsy to monitor disease progression.

Lupus nephritis (LN) remains a major cause of morbidity and progression to chronic kidney disease in systemic lupus erythematosus. Beyond immunosuppression, emerging evidence highlights the critical role of nephron-protective therapies in mitigating chronic damage and preserving renal function. This narrative review included a structured literature search in PubMed, EMBASE, and Web of Science for new cardio-renoprotective therapies in LN. Agents targeting metabolic, hemodynamic, and inflammatory pathways, including sodium-glucose cotransporter 2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1 RA), and nonsteroidal mineralocorticoid receptor antagonists (ns-MRAs), have shown renal and cardiovascular benefits in proteinuric and diabetic populations, and recent data suggest potential efficacy in LN. These therapies reduce intraglomerular pressure, proteinuria, oxidative stress, and tubular inflammation, complementing the immunomodulatory effects of standard regimens. In addition, endothelin receptor antagonists and novel anti-fibrotic or metabolic modulators are under investigation for synergistic cardiorenal protection. Early integration of these agents may delay progression to end-stage kidney disease, improve systemic vascular health, and reduce long-term treatment burden. Future randomized trials specifically designed in LN cohorts are warranted to define optimal timing, combinations, and safety in the context of immunosuppression. Nephron-protective therapy represents a paradigm shift in LN management, from solely controlling autoimmunity toward preserving long-term renal structure and function through multi-system, cardio-renal protection.

Lupus nephritis (LN), a severe manifestation of systemic lupus erythematosus, is characterized by progressive renal inflammation and tissue injury. To define molecular mechanisms underlying LN progression, we analyzed temporal and spatial transcriptomic profiles in kidneys of lupus-prone New Zealand Black/White F1 mice at 10, 20, and 30 weeks of age, representing preclinical, early, and advanced disease stages. Bulk RNA sequencing revealed minimal transcriptional changes between 10 and 20 weeks but marked shifts by 30 weeks, coinciding with overt nephritis. Differential expression and pathway analyses demonstrated significant upregulation of genes involved in immune cell recruitment, B-cell activation, cytokine signaling, fibrosis, and oxidative stress. To assess translational relevance, we mapped a curated human LN gene signature to orthologous mouse genes. Most orthologs showed significant temporal correlation with disease progression, indicating cross-species concordance and reinforcing the clinical relevance of the model. Spatial transcriptomics of 30-week kidneys identified 9 spatial clusters with distinct expression profiles, including regions enriched for B cells and myeloid cells. One cluster showed high expression of immunoglobulin genes and lymphocyte recruitment markers. Spatial molecular signature analysis identified inflammatory programs enriched for cytokine/chemokine and interferon pathways. Immunofluorescence confirmed peritubular TNFRSF1A expression, CCR5+ inflammatory cell accumulation, compartmentalized NRF2-HMOX1 responses, and CXCL13-associated tertiary lymphoid structure formation. These findings define stage-specific molecular programs and spatially organized immune niches in LN, providing mechanistic insight and potential targets for early intervention.

Systemic lupus erythematosus (SLE) is characterized by the immune system producing autoantibodies that target the body's own cells and tissues, leading to inflammation and tissue damage. Sphingosine-1-phosphate receptor 1 (S1PR1) plays a crucial role in regulating immune cell trafficking, and its function relies on a gradient of sphingosine-1-phosphate (S1P). During inflammatory immune responses, the S1P gradient is altered, promoting lymphocyte migration to inflammatory sites. Consequently, S1PR1 has become a therapeutic target for inhibiting lymphocyte egress from lymphoid tissues in autoimmune and inflammatory diseases. However, knowledge of S1PR1 expression and function in B cell subsets and antibody-secreting cells (ASCs) in SLE remains limited. Peripheral blood mononuclear cells (PBMCs) from forty-nine patients with SLE were enrolled to assess S1PR1 expression in B cell subsets and plasma cells. Significant differences in surface S1PR1 expression on activated naive (aNAV), Double Negative 2 (DN2) B cells and ASCs were further analyzed for correlations with disease activity, Lupus Nephritis (LN) involvement, inflammatory markers, S1P levels, and chemokine receptor expression. Intracellular S1PR1 expression was significantly increased across all B cell subsets, including naive (rNAV and aNAV), memory (SWM, USM, DN1, DN2), and ASCs. In contrast, surface S1PR1 expression differed markedly among subsets, with downregulation observed in aNAV and DN2 B cells and upregulation in ASCs. Further analysis revealed that surface S1PR1 downregulation on aNAV B cells was significantly associated with active disease status, SLEDAI-2K scores, and LN involvement. Inflammatory markers (IL-6, IL-8, and C3c levels) showed no correlation with surface S1PR1 expression, whereas erythrocyte sedimentation rate (ESR) demonstrated a significant negative correlation. In addition, lupus aNAV and DN2 B cells exhibited reduced surface CXCR3 expression without correlation to S1PR1 expression, whereas other B cell subsets in SLE subjects showed a significant correlation between CXCR3 and S1PR1 expression. Surface S1PR1 expression was downregulated in aNAV and DN2 B cells. Clinically, decreased surface S1PR1 expression on aNAV B cells was significantly correlated with active status, increased disease activity, LN involvement, and elevated ESR. The increased S1P levels, along with S1PR1 and CXCR3 downregulation, suggest that chronic activation characteristic of SLE may drive S1PR1 desensitization or internalization in aNAV B cells, thereby altering their ability to dynamically recirculate or respond to inflammation-associated signal target tissues.

PurposeSystemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterized by immune dysregulation, inflammation, and organ damage, particularly affecting the kidneys. This study aimed to investigate the role of miR-429 and its target gene SORT1 in the pathogenesis of SLE, focusing on their effects on immune cell balance, inflammation, and kidney injury.MethodsDifferential expression of miRNAs in SLE and lupus nephritis (LN) was analyzed using the GEO database, with identifying miR-429 as a potential regulator. In vitro, human mesangial cells (HMCs) were treated with TGF-β1 to investigate the effects of miR-429 and SORT1 on HMCs function in SLE. In vivo, a MRL/lpr mice were used as an SLE model to assess the impact of miR-429 on immune cell populations, inflammatory cytokine levels, and kidney pathology. Various assays, including qPCR, flow cytometry, CCK-8, and histological staining, were employed to evaluate gene expression, cell proliferation, and tissue damage.ResultsmiR-429 was downregulated in SLE patients and identified as a regulator of SORT1. In vitro, miR-429 expression decreased while SORT1 expression increased in TGF-β1-treated HMCs. Overexpression of miR-429 inhibited HMCs proliferation and reduced levels of IL-1β, IL-6, and TNF-α; however, these effect were reversed by SORT1 overexpression. In vivo, miR-429 treatment alleviated kidney damage in SLE mice, decreased levels of inflammatory cytokines, urinary albumin, uACR, SCr, and BUN, increased levels of Nephrin, Podocin, and WT1, and improved kidney histology. Conversely, co-overexpression of miR-429 and SORT1 attenuated these protective effects. Furthermore, miR-429 overexpression restored the balance between Th17 and Treg cells in SLE mice, whereas SORT1 overexpression suppressed this restoration.ConclusionmiR-429 targets SORT1 to modulate immune responses, reduce inflammation, and protect against kidney damage in SLE, suggesting that targeting the miR-429/SORT1 axis may offer a promising therapeutic strategy for SLE.