Lupus Nephritis Patients Research Articles

Decreased prevalence and altered clinical phenotype of systemic sclerosis and other autoimmune connective tissue diseases in type 1 and type 2 diabetes: A cross-sectional observational study.

Evidence has demonstrated that autoimmune diseases tend to coexist at a higher rate than expected, reflecting a common pathogenic pathway. In this study, we investigate the co-occurrence of systemic sclerosis, systemic lupus erythematosus, and Sjogren syndrome in patients with type 1 and type 2 diabetes mellitus. Our data were obtained using the 2019 Healthcare Cost and Utilization Project, and International Classification of Diseases, 10th Revision diagnosis codes were used to identify patients with systemic sclerosis, systemic lupus erythematosus, lupus nephritis, and Sjogren syndrome, as well as patients with type 1 and type 2 diabetes. We utilized Statistical Analysis System 9.4 for all analyses and included designated weight values to produce nationally representative estimates. The prevalence of systemic sclerosis among patients with type 1 diabetes mellitus and type 2 diabetes mellitus was significantly lower than that for the non-diabetes mellitus control group (0.0007% vs 0.09%, p-value = 0.0064 and 0.01% vs 0.07%, p-value < 0.0001), respectively. Similarly, there was a significant decrease in the prevalence of systemic sclerosis with lung involvement in patients with type 1 and type 2 diabetes mellitus, with a statically significant difference in type 2 diabetes mellitus versus nondiabetic group (0.001% vs 0.006%, p-value < 0.0001). We noted a similar pattern regarding the prevalence of systemic lupus erythematosus and lupus nephritis in patients with type 1 and 2 diabetes. Similarly, there was a significant decrease in the prevalence of Sjogren syndrome in patients with type 1 diabetes and type 2 diabetes. The collected data demonstrates an inverse relation between some autoimmune connective tissue diseases and diabetes. This suggests that these diseases and diabetes mellitus may have different immune pathogenesis. There was also a significantly lower incidence of organ complications such as lupus nephritis and systemic sclerosis lung disease among patients with diabetes, suggesting that diabetes and treatment of diabetes may alter the clinical expression of these disorders.

Potential role of bacterial extracellular vesicles in the pathophysiology of systemic lupus erythematosus

Systemic Lupus Erythematosus (SLE) is a rare autoimmune disorder influenced by various factors, including infections. Following bacterial or viral infections, there is an increase in IFN-I production, primarily by plasmacytoid dendritic cells (pDCs). Overproduction of IFN-I has been shown to drive the progression of SLE. Recent findings indicate that the gene expression signature of IFN-I in lupus nephritis patients does not co-occur with pDCs as expected; instead, it is localized in glomerular regions with anastomosing capillaries, suggesting a potential source from the blood. T cells, natural killer cells, and myeloid lineage cells may also secrete IFN in the bloodstream. Bacterial presence in the bloodstream challenges the concept of blood sterility, raising the possibility that cell-free microbial components, such as bacterial extracellular vesicles (BEVs), could trigger excessive IFN production through systemic circulation. While existing studies suggest a role for BEVs in human SLE, experimental evidence has yet to establish a direct association between the entire BEV nanoparticle and the disease. Research has primarily focused on (1) mammalian EVs and (2) purified eDNA and other specific cargoes as contributors to SLE progression. It remains unproven whether these bacterial molecules exert their effects while associated with vesicular membranes, i.e., BEVs. We hypothesize that BEVs, which carry diverse cargoes including nucleic acids, may enter systemic circulation, induce cellular responses leading to IFN overproduction, and exacerbate SLE severity. Clinical studies could investigate the association of BEVs with SLE progression by monitoring their presence and quantity in blood samples and correlating these factors with disease outcomes. Furthermore, understanding the involvement of BEVs may aid in identifying SLE biomarkers, inform infection prevention strategies, and inspire the development of BEV-neutralizing agents.

The effect of circulating cytokines on the risk of systemic lupus erythematosus: Mendelian randomization and observational study.

Systemic lupus erythematosus (SLE) is a complex autoimmune disorder, the etiology of which involves the alterations in circulating cytokine levels. However, the cause-and-effect relationships and in-depth clinical relevance of them remain to be systematically investigated. We conducted a two-sample Mendelian randomization (MR) study to assess the causality of circulating cytokine levels and SLE and found that genetically determined elevated CTACK and IL-18 were associated with an increased risk of SLE, whereas a higher level of GRO-a was associated with decreased risk. Furthermore, we performed an observational study to further reveal the association between 27 cytokines and the severity measured by SLEDAI score, as well as lupus nephritis (LN), of SLE. We identified six cytokines (MCP1, MIP1β, CTACK, IP10, HGF, IL18, IL13) that were identified as associated with the clinical severity of SLE, and five cytokines, especially IL18, were related with LN and may have good diagnostic value. Moreover, we also predicted four compounds that might have good binding activities with IL18. The evidence supported a potential causal role of circulating cytokines on the risk of SLE. Targeting IL18 might be a meaningful strategy for the prevention or treatment of SLE, especially in LN patients.

Antagonising Yin Yang 1 ameliorates the symptoms of lupus nephritis via modulating T lymphocyte signaling

Lupus nephritis (LN) is a chronic complication of systemic lupus erythematosus (SLE). At present, no drugs are capable of delaying the progression of LN without a risk of serious side effects. There is thus a pressing need for further studies of LN pathogenesis to identify novel therapeutic targets and aid in the development of new approaches to treating this debilitating disease. In this study, a multi-omics approach was used to characterize the pathogenesis of LN and to identify disease-related targets, ultimately leading to the identification and validation of Yin Yang 1 (YY1) as a promising therapeutic target in LN. A rapid approach to efficiently screening for candidate YY1 ligands was implemented using drug databases that established rebamipide as a YY1 antagonist suitable for use in the management of LN. Specifically, the YY1 antagonist activity of rebamipide was found to regulate lymphocyte activity, reduce autoantibody production, limit immune complex deposition, and suppress macrophage activation while improving symptoms in a murine model of LN. Results supportive of a similar pathologic mechanism of action were also obtained when analyzing renal tissue sections from LN patients, underscoring the potential clinical significance of YY1 and its antagonist rebamipide, suggesting that rebamipide may have positive effects on lymphocytes and may improve symptoms in treated patients. This study provides a robust foundation for further research focused on the pathogenesis and treatment of LN.

Comparative Analysis of C4d Deposition with The Severity, Laboratory Results and Histopathologic Scores in Lupus Nephritis

Background: Lupus nephritis (LN) is a serious complication of systemic lupus erythematosus (SLE) and evident in 60% of patients. Complement system and its product, complement component 4 degradation (C4d), plays an important role in the pathogenesis of LN. The aim is to determine the prognostic value of C4d detection in different classes of LN and correlation with laboratory results and histopathologic activity score. Methods: Thirty-five patients with LN were collected between January to September 2023. Blood levels of anti-nuclear antigens (ANA), anti-double stranded DNA antibody (Anti-dsDNA), C3, C4, and 24hr urine protein were measured. Renal tissue biopsy was examined regarding glomerular C4d antibody immunohistochemical staining and Classes of LN according to International society of nephrology/Renal Pathology Society (ISN/RPS). Results: Glomerular C4d was expressed in 40% of LN patients and was significantly correlated with urinary protein excretion (p=0.001) and Anti-dsDNA antibody (P=0.048), but not with LN classes or activity score or low complements. Conclusions: Glomerular C4d deposition of LN does not indicate the present disease activity but may help to identify a subset of patients with worse renal prognosis, providing insights about the therapeutic approaches for SLE with LN. Keywords: Lupus nephriti, glomerular C4d, proteinuria, Anti-double stranded DNA Antibody.

Renal remission status and long-term renal survival in lupus nephritis patients

Aim of the workTo compare long-term renal survival in lupus nephritis (LN) patients who achieved complete (CR), partial (PR), or no remission following LN induction therapy. Patients and methodsEligible patients with biopsy-proven LN were categorized into ordinal (CR, PR, or no remission) or binary (remission or no remission) at 6, 12, 24, 36 months post diagnosis according to modified Aspreva Lupus Management Study (mALMS) criteria. The primary endpoint was long-term renal survival. ResultsThe study included 161 patients with LN, with a mean age 36.3 ± 8.2 years, age at biopsy 26.2 ± 7.4 years; 146 females and 15 males (F:M 9.3:1). All patients received induction therapy 6 months before or after biopsy with follow up duration ≥3 years. 114 (70.8 %) patients achieved long term survival, while 47 (29.2 %) ended up with end-stage renal disease (ESRD). Those with CR were more likely to have long-term survival (p < 0.001). A significant relation was found between maintenance therapies at different time points in those receiving azathioprine (AZA) (p = 0.002, p = 0.011, p = 0.016 and p = 0.003 respectively), as well as hydroxychloroquine (HCQ) (p < 0.003, p < 0.001, p = 0.011, p < 0.001 and p < 0.001 respectively) with long term survival. Cardiovascular and neuropsychiatric manifestations were significantly associated with ESRD/mortality (p = 0.003 and p = 0.002 respectively). The most significant predictor of long-term survival was complete remission at 6 months (β-3.745, p = 0.025). ConclusionIn LN, renal remission was significantly associated with long term renal survival. Receiving AZA and HCQ have a significant association and CR at 6 months was the best predictor for long-term survival in LN patients.

Prevalence and risk factors of osteoporosis in lupus nephritis patients in China: a cross-sectional study

BackgroundOsteoporosis is a significant concern among individuals with lupus nephritis (LN), with reported prevalence rates exhibiting considerable variation. This study investigates the prevalence and identifies risk factors contributing to osteoporosis in premenopausal and postmenopausal LN patients, addressing the paucity of data specific to the Chinese population.MethodsThis cross-sectional study enrolled patients with renal biopsy-proven LN, who underwent bone mineral density (BMD) measurements using dual X-ray absorptiometry at the lumbar spine, total hip, and femoral neck. The study was conducted at Tongji hospital from May 2011 to June 2018.ResultsA total of 130 patients were evaluated, with a mean age of 46.2 ± 12.9 years, including 2 males and 128 females. A significant majority, 52.3% (n = 67) of the female patients, were identified as postmenopausal. BMD measurements revealed that 40.0% of patients had osteoporosis in at least one site. The spearman rank correlation of BMD with clinical characteristics indicated that age at menopause, weight, height, and body mass index were positively correlated with BMD, while age, age at diagnosis of LN, and menopause duration were negatively correlated with BMD in lumbar spine, total hip, and/or femoral neck. Multivariable linear regression analysis demonstrated that body mass index was positively associated with BMD, whereas disease duration and menopause duration were negatively associated with BMD in all and postmenopausal patients. Postmenopausal patients consistently had a higher prevalence of osteoporosis across all measured sites. Factors such as older age, lower weight, and the absence of bisphosphonates therapy were independently associated with an increased risk of osteoporosis in LN patients.ConclusionOur findings underscore a substantial prevalence of osteoporosis in LN patients, especially among postmenopausal individuals. The study identifies older age, lower weight, and absence of bisphosphonates treatment as risk factors for osteoporosis in this patient population.

Predictive value of residual active histologic lesions on renal flare in lupus nephritis patients with clinical remission

Abstract Background Renal flare in lupus nephritis (LN) is a crucial contributing factor to poor kidney outcomes. This study aimed at evaluating the predictive value of residual active histologic lesions on renal flare in proliferative LN patients with clinical remission. Methods We retrospectively enrolled LN patients with class III/IV±V (biopsy 1) who had undergone a protocol repeat biopsy (biopsy 2) at 7.3 (IQR: 6.5, 8.4) months after induction therapy with clinical remission and experienced renal flare within 3 years or had been followed up for at least 3 years without renal flare after biopsy 2 with maintenance therapy from two kidney units in China. Results A total of 114 eligible patients were included, 28 (24.6%) of whom developed a renal flare. Activity index (AI) at biopsy 2 was significantly associated with LN flare (P &amp;lt; 0.0001). If AI&amp;gt;1, the OR for LN flare was 23.1 (95%CI, 5.1-103.8, P&amp;lt;0.001). For patients with partial clinical remission compared with those with complete clinical remission, the OR for LN flare was 3.0 (95%CI: 1.1-8.3, P=0.029). Multivariate analysis showed that anti-dsDNA positivity, presence of cellular/fibrocellular crescent and endocapillary hypercellularity at biopsy 2 were independent risk factors for LN flare. When residual active histologic lesions were added to clinical variables, the area under the curve (AUC) of the prediction model for LN flare significantly increased and the misclassification rate significantly decreased. Conclusions Renal flare in LN patients with clinical remission is strongly associated with the residual active histologic lesions.

Diagnostic model of microvasculature and neurologic alterations in the retina and optic disc for lupus nephritis

BackgroundMachine learning (ML) analysis of retinal nerve fiber layer (RNFL) thickness and vessel density (VD) alterations in the macular region and optic disc may provide a new diagnostic method for lupus nephritis (LN). This study aimed to assess these alterations in LN patients using optical coherence tomography angiography (OCTA). MethodsA retrospective analysis was conducted on 81 systemic lupus erythematosus (SLE) patients without retinopathy, divided into two groups: LN (41 patients) and non-LN (39 patients). OCTA imaging was performed on all participants. Independent risk factors were identified through univariate and multivariate analyses, followed by the development of a random forest (RF) diagnostic model. ResultsA total of 37 RNFL and VD variables from the macular region and 23 from the optic disc were analyzed. Through elastic net regression, 16 significant factors were identified. Further multivariate logistic regression selected 8 critical factors, which were used to construct the RF model. The RF model achieved an area under the curve (AUC) of 0.950 (95 % CI: 0.882 to 1.000), accuracy of 0.903 (95 % CI: 0.743 to 0.980), sensitivity of 0.867, specificity of 0.938, a positive predictive value (PPV) of 0.929, and a negative predictive value (NPV) of 0.882. ConclusionThis study highlights the potential of ML-based OCTA data in diagnosing LN. Key diagnostic factors included perimeter (PERIM), superficial capillary plexus vessel density (SVD) - parafoveal (para)-temporal (T), SVD-perifoveal (peri)-inferior (I), RNFL-Fovea, RNFL-Peri, RNFL-Peri-T, capillary-whole-image, and peripapillary RNFL (PRNFL)- inferonasal (IN).

GSTA1 gene polymorphisms are associated with cyclophosphamide effectiveness in lupus nephritis patients: A case-control study in Indonesia

Glutathione-S-transferase alpha-1 (GSTA1) is an enzyme with high conjugation activity against aldophosphamide, a metabolite of cyclophosphamide and promoter polymorphisms in GSTA1 may influence the cyclophosphamide effectiveness. The aim of this study was to evaluate the effectiveness and side effects of cyclophosphamide in lupus nephritis patients, using GSTA1 variants as predictors. A case-control study was conducted at Hasan Sadikin Hospital, Bandung, Indonesia, involving 100 lupus nephritis patients from February 2023 to January 2024. The PCR-Sanger sequencing was used to genotype five selected single nucleotide polymorphisms (SNPs) in the GSTA1 promoter: -52 A&gt;G, -69 T&gt;C, -513 A&gt;G, -567 G&gt;T, and -631 G&gt;T. The endpoint was assessed after six doses of cyclophosphamide by evaluating renal function, disease activity and side effects. Results indicated that six doses of intravenous cyclophosphamide treatment improved renal function and disease activity in the patients, as evidenced by significant changes in serum creatinine (0.79 vs 0.69 mg/dL), dipstick proteinuria (3.00 vs 1.50), creatinine clearance (98.50 vs 109.50 mL/min), and Modified Systemic Lupus Erythematosus Disease Activity Index 2000 (M-SLEDAI-2K) score (8.61 vs 6.95). The AG genotype at -513 A&gt;G was associated with reduced cyclophosphamide effectiveness (odds ratio (OR): 0.19; 95%CI: 0.19–0.60; p=0.019). The GT genotype at -631 G&gt;T independently increased the progression of anemia (OR: 2.41; 95%CI: 0.26–22.12; p=0.040). This study highlights that the presence of GSTA1 variants affected cyclophosphamide effectiveness in lupus nephritis patients, with heterozygous polymorphisms at -513 (AA to AG) and -631 (TT to GT) predicting reduced effectiveness of cyclophosphamide by enhancing GSTA1 promoter activity, while anemia further exacerbated lupus nephritis disease severity. GSTA1 polymorphism was not associated with the presence of alopecia, amenorrhea, gastrointestinal disorders, and leukopenia during cyclophosphamide therapy.

Oxymatrine Ameliorates Lupus Nephritis by Targeting the YY1-Mediated IL-6/STAT3 Axis.

Lupus nephritis (LN) is a severe form of systemic lupus erythematosus (SLE), characterized by inflammation in the renal glomeruli and tubules. Previous research has demonstrated that dihydroartemisinin (DHA) can reduce inflammatory damage in LN mouse models. Oxymatrine, which has similar biological properties to DHA, may also provide therapeutic benefits. This study aims to investigate the effects of oxymatrine on LN using a murine model and examines its molecular mechanisms through an analysis of microarray datasets from LN patients. The analysis identified differentially expressed genes (DEGs) in renal tissues, regulated by the transcription factor Yin Yang 1 (YY1), which was found to be significantly upregulated in LN patient kidneys. The results indicate that oxymatrine targets the YY1/IL-6/STAT3 signaling pathway. In cell models simulating renal inflammation, oxymatrine reduced YY1 expression and inhibited the secretion of inflammatory factors (IFs), thereby diminishing inflammation. YY1 is crucial in modulating IFs' secretion and contributing to LN pathogenesis. Additionally, oxymatrine's interaction with YY1, leading to its downregulation, appears to be a key mechanism in alleviating LN symptoms. These findings support oxymatrine as a promising therapeutic agent for LN, offering new avenues for treating this autoimmune kidney disorder.

Real-world data in lupus nephritis: results from a European survey on renal function testing and burden of disease progression

Objective Patients with lupus nephritis (LN), a severe renal manifestation of systemic lupus erythematosus, should be monitored for progression of chronic kidney disease to end-stage renal disease but data on renal function testing in LN patients are limited. This real-world analysis aimed to evaluate nephrologists’ use of renal function tests to support LN diagnosis and monitoring and to examine the impact of disease progression in LN patients in Europe. Methods Data were drawn from the Adelphi Lupus Disease Specific Programme, a cross-sectional survey of nephrologists and their next five consulting patients with LN in France, Germany, Italy, Spain, and the United Kingdom in 2021. Nephrologists provided demographic and clinical information for each patient and the same patients completed a self-reported questionnaire. Using a checkbox, patients provided informed consent to take part in the survey. Results Nephrologists (n = 72) provided data on 376 patients with LN. Estimated glomerular filtration rate (eGFR) or proteinuria testing was not undertaken in around 10% and 50% of these patients, respectively. Regression analysis predicted reduction in renal function (disease progression) following LN diagnosis whilst bivariate analyses showed significantly worse outcomes for patients with progressed disease: worse pain, fatigue, treatment satisfaction, and patient-reported health state and activity impairment. Conclusion Our study revealed lower-than-expected nephrologist-reported use of renal function testing to support diagnosis/monitoring of patients with LN in real-world clinical settings in Europe. Lower quality of life (QoL) was observed in patients with more progressed disease. Increased use of renal function testing is needed so that all LN patients are monitored closely to manage disease progression and avoid the associated QoL impact.

Outgrowth of Escherichia is susceptible to aggravation of systemic lupus erythematosus

BackgroundSystemic lupus erythematosus (SLE) is linked to host gut dysbiosis. Here we performed faecal gut microbiome sequencing to investigate SLE-pathogenic gut microbes and their potential mechanisms.MethodsThere were 134 healthy controls (HCs) and 114 SLE cases for 16 S ribosomal RNA (rRNA) sequencing and 97 HCs and 124 SLE cases for shotgun metagenomics. Faecal microbial changes and associations with clinical phenotypes were evaluated, and SLE-associated microbial genera were identified in amplicon analysis. Next, metagenomic sequencing was applied for accurate identification of microbial species and discovery of their metabolic pathways and immunogenic peptides both relevant to SLE. Finally, contribution of specific taxa to disease development was confirmed by oral gavage into lupus-prone MRL/lpr mice.ResultsSLE patients had gut microbiota richness reduction and composition alteration, particularly lupus nephritis and active patients. Proteobacteria/Bacteroidetes (P/B) ratio was remarkably up-regulated, and Escherichia was identified as the dominantly expanded genus in SLE, followed by metagenomics accurately located Escherichia coli and Escherichia unclassified species. Significant associations primarily appeared among Escherichia coli, metabolic pathways of purine nucleotide salvage or peptidoglycan maturation and SLE disease activity index (SLEDAI), and between multiple epitopes from Escherichia coli and disease activity or renal involvement phenotype. Finally, gavage with faecal Escherichia revealed that it upregulated lupus-associated serum traits and aggravated glomerular lesions in MRL/lpr mice.ConclusionWe characterize a novel SLE exacerbating Escherichia outgrowth and suggest its contribution to SLE procession may be partially associated with metabolite changes and cross-reactivity of gut microbiota-associated epitopes and host autoantigens. The findings could provide a deeper insight into gut Escherichia in the procession of SLE.

ITreg cells-secreted IL10 alleviates lupus nephritis through inactivating lncRNA HAR1A transcription to suppress SMARCD1-mediated iNOS activation

Lupus nephritis (LN) is a highly prevalent complication of systemic lupus erythematosus (SLE). Long non-coding RNAs (lncRNAs) are essential modulators in multiple types of human diseases, including LN. In the current study, we searched on online GEO database to select out lncRNAs that were differentially expressed in blood samples of LN patients. Through further RT-qPCR analysis, we found that lncRNA Highly Accelerated Region 1 A (HAR1A) is most significantly upregulated in blood samples of LN patients. Functionally, we detected that overexpression of HAR1A could aggravate LPS-induced injury and inflammation. According to the results of bioinformatics analysis and mechanism experiments, we determined that HAR1A binds with miR-149-3p to upregulate SMARCD1 through competing endogenous RNA (ceRNA) mechanism. It has been proven that iNOS is an inflammation inducer. Here, we found that HAR1A/miR-149-3p/SMARCD1 upregulates iNOS expression through enhancing H3K27ac level in iNOS promoter. Previously, we proved that CD8+CD103+ iTreg cells could alleviate glomerular endothelial cell injury. Moreover, we demonstrated that CD8 + CD103+ iTreg cells-secreted IL-10 downregulated HAR1A expression by impeding NF-κB pathway activation. In conclusion, this study provides evidences revealing a novel molecular pathway blocked by CD8+CD103+ iTreg cells in LN.

OTUB1 regulation of ferroptosis and the protective role of ferrostatin-1 in lupus nephritis

Lupus nephritis (LN) is a prevalent and severe manifestation of systemic lupus erythematosus (SLE), leading to significant morbidity and mortality. OTUB1, a deubiquitinating enzyme, has emerged as a potential therapeutic target due to its role in cellular protection and regulation of ferroptosis, a form of cell death linked to LN. Our study revealed significantly reduced OTUB1 expression in the glomeruli of LN patients and podocytes, correlated with disease severity. CRISPR/Cas9-mediated OTUB1 knockout in podocytes resulted in pronounced injury, indicated by decreased levels of nephrin and podocin. Ferrostatin-1 treatment effectively mitigated this injury, restoring SLC7A11 expression and significantly reducing MDA levels, Fe2+ levels, BODIPY C11 expression, and normalized cysteine and glutathione expression. In the MRL/lpr mouse model, Ferrostatin-1 significantly improved renal function decreased proteinuria, and ameliorated renal histopathological changes, including reduced glomerular endothelial swelling, mesangial cell proliferation, and leukocyte infiltration. These results underscore the protective role of Ferrostatin-1 in modulating the pathogenesis of LN. OTUB1 plays a crucial protective role against podocyte injury in LN by regulating ferroptosis. Ferrostatin-1 effectively mitigates podocyte damage induced by OTUB1 deficiency, suggesting that targeting ferroptosis could be a promising therapeutic strategy for LN.

The value of renal color Doppler ultrasound as an objective tool in the diagnosis of renal affection in SLE patients

BackgroundSystemic lupus erythematosus (SLE) is an autoimmune disease with diverse manifestations, which resembles a clinical challenge to be managed. Lupus nephritis is a life-threatening condition as about 10% of patients develop chronic kidney disease.Aim of the workTo assess the role of resistive index (RI) as a noninvasive parameter in detecting renal affection in SLE patients.ResultsA case–control study included 3 matched groups: 30 patients, 15 SLE with no renal affection, and 15 SLE lupus nephritis patients, who were selected, diagnosed according to ACR criteria 2019 for SLE, beside 15 age- and gender-matched healthy controls without any risk factors of chronic diseases. Written informed consent was obtained from all the three groups, and the study was approved by ethical committee. There was a statistically significant increase in both SLEDAI and renal SLEDAI scores, serum BUN, creatinine, urinary pus cells, RBCs, casts and proteins, 24-h urinary proteins, and protein/creatinine ratio beside a statistically significant increase in both right and left resistive indices in the group of lupus nephritis than the other group. There was highly statistically significant difference between SLE without nephritis and SLE with nephritis regarding renal echogenicity. There was statistically significant positive correlation between average RI and SLEDAI, rSLEDAI, serum creatinine, BUN, 24-h urinary proteins, protein/creatinine ratio, and renal echogenicity. Relation between renal echogenicity and demographic, laboratory, and clinical data was highly statistically significant with rSLEDAI, serum creatinine, BUN, 24-h urinary proteins, and P/C ratio. Our study highlighted that the best cutoff point of Rt average RI to detect SLE with nephritis group was found > 0.68 with sensitivity of 86.7% and specificity of 100.0%, while the best cutoff point of left average RI to detect SLE with nephritis group was found > 0.7 with sensitivity of 80.0% and specificity of 100.0%.ConclusionRenal RI is a noninvasive technique that can be used for detection renal disease activity in SLE patients, together with renal parenchymal echogenicity by grayscale US.

Plasma exosomes may mediate the development of lupus nephritis in patients with systemic lupus erythematosus.

Lupus nephritis (LN) is the most serious complication of systemic lupus erythematosus (SLE), and plasma exosomes may serve as a bridge. MicroRNAs (miRNAs) are abundant in exosomes, so this study aimed to explore the role of exosome-derived miRNA in the development of LN. The publicly available data containing plasma exosomal miRNAs in SLE patients and healthy controls were researched, and differential expression and functional enrichment analysis of exosomal miRNA was conducted. Then, plasma exosomes from SLE patients were extracted, and the accuracy of differential expression and functional enrichment analysis was preliminarily verified. PKH26 dye was used to label exosomes to detect whether exosomes can enter HK2 cells. Evaluation of plasma exosomes impact on cell viability was done by utilizing CCK-8 assay. Flow cytometry was used to measure cell apoptosis. Plasma exosomes were successfully extracted and identified. Through differential expression analysis of the pulbilic data and subsequent qPCR validation, we observed that miR-20b-5p is overexpressed in plasma exosomes of SLE patients, whereas miR-181a-2-3p is downregulated. Then functional enrichment analysis revealed that these differential miRNAs primarily regulate processes such as apoptosis, autophagy, and inflammation. Then, flow cytometry analysis conducted after co-incubation of plasma exosomes and peripheral blood mononuclear cells confirmed that exosomes can indeed regulate apoptosis. And plasma exosomes can successfully enter HK2 cells without affecting cell activity. In addition, plasma exosomes promote HK2 cell apoptosis and autophagy. Overexpression of miR-181a-2-3p could inhibit HK2 cells apoptosis and upregulate the expression of bcl2, and beclin1. At the same time, a trend towards increased apoptosis rates was observed in HK2 overexpressed miR-20b-5p, although the difference did not reach statistical significance. And miR-20b-5p can enhance the expression of caspase3 and becin1 while suppressing the expression of bcl2 and LC3β. Our research indicates that the abundant presence of miR-20b-5p and the depletion of miR-181a-2-3p in plasma exosomes of SLE patients may mediate the promotion of apoptosis and autophagy in HK2 cells, thereby causing kidney damage and the development of LN.

Antimalarials in Lupus Nephritis: How Strong is the Evidence?

Systemic lupus erythematosus is a chronic multisystem autoimmune disease that affects the kidneys in approximately 50% of patients, with prevalence rising to as high as 70% in certain populations, such as African Americans and Asians. Antimalarials -and particularly hydroxychloroquine- are currently considered a mainstay of therapy, together with immunosuppressants. Over the last decades, several studies have extensively investigated the mechanisms of action of antimalarial agents, and their potential beneficial properties in patients with SLE in general. However, the evidence for the therapeutic benefit of hydroxychloroquine in patients with lupus nephritis (LN) derives mainly from observational studies, conducted in an era prior to the refinement of induction and maintenance protocols for immunosuppressive therapy. Despite the paucity of high-quality evidence on its efficacy in LN, the nephrology community widely supports the universal use of hydroxychloroquine in LN patients, and recommendations for its use are firmly entrenched in various clinical practice guidelines. Nonetheless, the use of antimalarials may also carry inherent risks, underscoring the importance of personalized approaches in these patients. Herein, we comprehensively review the available literature on antimalarials in LN aiming to update the current evidence, limitations, and future perspectives for the use of antimalarials in adults.

Sex differences in mortality among patients with lupus nephritis

ObjectiveTo evaluate the prognostic importance of sex in lupus nephritis (LN).MethodsA retrospective cohort of 1048 biopsy-confirmed LN patients, diagnosed between January 1, 1996, and December 31, 2018, was analyzed. Demographics, clinical characteristics, laboratory findings, and renal pathology were assessed. The primary outcome was mortality, and the secondary outcomes included doubling of serum creatinine and end-stage renal disease (ESRD). Sex-associated risks were evaluated using Cox regression models.ResultsAmong the1048 patients, 178 (17%) were male and 870 (83%) were female. Male patients exhibited more aggressive features: higher blood pressure, earlier disease onset, and elevated levels of serum creatinine (Scr), uric acid, blood urea nitrogen. Intriguingly, male patients also displayed more severe histopathological alterations, such as more total crescents, cellular crescents formations, higher level of glomerular leukocyte infiltration and Activity Index (AI), even when overall renal pathology was comparable between sexes. During a median follow-up of 112 months, mortality was registered in 141 patients (15.3%). Mortality rates were conspicuously higher in males (24.2% males vs. 13.4% females, p = 0.0029). Secondary outcomes did not show significant sex differences. Cox regression analysis highlighted male, age of renal biopsy, eGFR, and Chronicity Index (CI) as independent risk factors for survival in LN patients. Notably, infections emerged as the leading cause of mortality among LN patients, with a significant higher rate in male patients.ConclusionIn our cohort with LN, there was a higher rate of all-cause mortality and proportion of infection-related death in male. Recognizing and further exploring these sex disparities is crucial for optimized LN patients care.Graphical

Urine Extracellular Vesicles Size Subsets as Lupus Nephritis Biomarkers.

Systemic lupus erythematosus (SLE) is an autoimmune disorder that often leads to kidney injury, known as lupus nephritis (LN). Although renal biopsy is the primary way to diagnose LN, it is invasive and not practical for regular monitoring. As an alternative, several groups have proposed urinary extracellular vesicles (uEVs) as potential biomarkers for LN, as recent studies have shown their significance in reflecting kidney-related diseases. As a result, we developed a flow cytometry approach that allowed us to determine that LN patients exhibited a significantly higher total uEV concentration compared to SLE patients without kidney involvement. Additionally, an analysis of different-sized uEV subsets revealed that microvesicles ranging from 0.3 to 0.5 μm showed the most promise for distinguishing LN. These findings indicate that evaluating uEV concentration and size distribution could be a valuable diagnostic and monitoring tool for LN, pending further validation in more comprehensive studies.