Disease Activity In Lupus Nephritis Research Articles

Serum antineutrophil cytoplasmic antibody positivity at the time of renal biopsy is associated with disease activity of lupus nephritis

Objective To investigate the correlations between serum antineutrophil cytoplasmic antibody (ANCA) and clinicopathological features, induction treatment response, and prognosis of lupus nephritis (LN) patients. Methods In this retrospective study, biopsy-proven LN patients from October 2010 to September 2020 were tested for serum ANCA by indirect immunofluorescence and ELISA and were divided into ANCA-positive group and ANCA-negative group. The clinicopathological data of the two groups were analyzed and compared. Results Thirty-five of 115 patients (30.43%) were seropositive for ANCA. ANCA-positive patients had significantly higher systemic lupus erythematosus activity index and activity index scores, higher 24-h urinary protein, and lower complement three levels (p = 0.001, 0.028, 0.023, 0.009, respectively). The incidences of oral ulcers, thrombocytopenia, and leukocyturia, and the positive rates of anti-dsDNA antibody and anti-histone antibody were significantly higher in ANCA-positive group (p = 0.006, 0.019, 0.012, 0.001, 0.019, respectively). Class IV LN and fibrinoid necrosis/karyorrhexis were significantly more common in the ANCA-positive group (p = 0.027, 0.002). There was no significant difference in the total remission rate of ANCA-positive patients receiving cyclophosphamide and mycophenolate mofetil as induction therapies (83.33% vs. 66.67%, p > 0.05), while patients receiving cyclophosphamide as induction therapy had a higher total remission rate than those receiving other immunosuppressants (83.33% vs. 20%, p = 0.028). Conclusions LN patients with ANCA seropositivity at renal biopsy have a significantly higher disease activity, and their pathological manifestations are predominantly proliferative LN. These patients require a more active immunosuppressive therapy with cyclophosphamide or mycophenolate mofetil to improve their remission rate.

Lupus nephritis: redefining the treatment goals

The course of proliferative lupus nephritis (LN) is characterized by flares of activity alternating with periods of quiescence, against a background of chronic immune dysregulation. An accurate assessment of disease activity is of unassailable importance to tailor therapy. In the present communication, we discuss the available clinical, serological and histological tools to evaluate disease activity and how they may be applied to redefine the treatment goals in LN. Traditionally, treatment response is judged by the degree of proteinuria reduction and improvement of kidney function, but this fails to differentiate ongoing inflammatory disease from chronic damage. Despite intensive research, no novel biomarker has proved useful for clinical practice, and we continue to rely on anti-double-stranded DNA antibody levels (anti-dsDNA) to assess serological activity. Repeat kidney biopsies sometimes reveal persistent inflammation despite apparent clinical remission, giving credibility to the conviction that histological remission should be a treatment goal and protocol biopsies part of the decision-making process. However, the discrepancies between clinical and histological responses to therapy can be explained by persistent systemic autoimmunity with low-grade immune complex deposition or, alternatively, by delayed clearance of intrarenal inflammation once immunological remission has been achieved. Since persistent immune dysregulation is the motor of disease activity in LN, it should be the principal focus of therapy and monitoring. We propose to replace the traditional induction-remission maintenance protocol by a more dynamic and individualized approach, and aim for 3 treatment goals, concomitantly rather than sequentially: 1) Clinical remission, by attenuating renal inflammation, using microscopic hematuria, proteinuria, eGFR and complement levels as biomarkers; 2) Immunological remission, by decreasing immune complex generation, using anti-dsDNA as biomarker; 3) Preservation of kidney function, by curtailing chronic kidney damage, using eGFR slope as biomarker.

Clinical significance of serum CXCL9, CXCL10, and CXCL11 in patients with lupus nephritis.

Lupus nephritis (LN) is an autoimmune disease as a complication of systemic lupus erythematosus (SLE). LN is typically diagnosed through a combination of clinical evaluation as index scoring, and kidney biopsy as a more accurate but invasive examination. In the current study, we assessed serological markers including IFN-γ-inducible chemokines C-X-C motif chemokine ligand (CXCL)9, CXCL10, and CXCL11 in diagnosing LN. A retrospective analysis was conducted on 160 SLE patients with and without LN. Fasting venous blood was collected from the study subjects for measuring serum levels of CXCL9, CXCL10, and CXCL11. The assessment of clinical disease activity in SLE was conducted using theSLE Disease Activity Index(SLEDAI)-2000 scoring system. LN disease activity was conducted using the Austin scoring system. LN was further confirmed following kidney biopsy, and data were compared by receiver operating characteristic(ROC) analysis. SLE patients with LN showed longer SLE duration, enhanced SLEDAI scores, lower serum anti-ds-DNA antibody levels when compared to SLE patients without LN. Specifically, these patients had significantly higher serum levels of CXCL9, CXCL10 and CXCL11. CXCL9, CXCL10, and CXCL11 showed positive correlation with SLE disease activity in SLE patients with LN. ROCanalysis of CXCL9, CXCL10, and CXCL11 showed substantial enhancement of sensitivity and specificity for the diagnosis of LN in the patients with SLE. Serum CXCL9, CXCL10, and CXCL11 levels may improve the sensitivity and specificity for the diagnosis of LN in SLE patients.

Investigating the value of urinary biomarkers in relation to lupus nephritis histopathology: present insights and future prospects.

Lupus nephritis (LN), a leading cause of death in Systemic Lupus Erythematosus (SLE) patients, presents significant diagnostic and prognostic challenges. Although renal pathology offers critical insights regarding the diagnosis, classification, and therapy for LN, its clinical utility is constrained by the invasive nature and limited reproducibility of renal biopsies. Moreover, the continuous monitoring of renal pathological changes through repeated biopsies is impractical. Consequently, there is a growing interest in exploring urine as a non-invasive, easily accessible, and dynamic "liquid biopsy" alternative to guide clinical management. This paper examines novel urinary biomarkers from a renal pathology perspective, encompassing cellular components, cytokines, adhesion molecules, auto-antibodies, soluble leukocyte markers, light chain fragments, proteins, small-molecule peptides, metabolomics, urinary exosomes, and ribonucleic acids. We also discuss the application of combined models comprising multiple biomarkers in assessing lupus activity. These innovative biomarkers and models offer insights into LN disease activity, acute and chronic renal indices, fibrosis, thrombotic microangiopathy, podocyte injury, and other pathological changes, potentially improving the diagnosis, management, and prognosis of LN. These urinary biomarkers or combined models may serve as viable alternatives to traditional renal pathology, potentially revolutionizing the method for future LN diagnosis and observation.

Potential involvement of circulating exosomal miRNA-146a in disease activity and TRAF6 gene expression in juvenile proliferative lupus nephritis

BackgroundJuvenile SLE (JSLE) is a complex autoimmune disorder that predominantly affects children and adolescents with several unique challenges, and microRNA-146a (miRNA-146a) might be an interesting anti-inflammatory molecule. Because exosomes in...

Association of serum Nrf2 protein levels with disease activity and renal impairment in lupus nephritis.

We aimed to investigate the relationship between nuclear factor erythroid 2-related factor 2 (Nrf2) protein expression levels, lupus nephritis (LN) disease activity, and the degree of renal injury (based on the estimated glomerular filtration rate [eGFR]) in patients with LN. We selected 40 healthy control participants and 102 patients with LN who were treated in the Second Hospital of Jilin University, China, for inclusion in this study. Patients with LN were classified into LN with high-eGFR and LN with low-eGFR groups. Nrf2 protein levels were measured in the serum and renal tissues of the participants in both groups to assess the correlation between Nrf2 protein levels and different LN disease states. There was a significantly positive correlation between serum Nrf2 protein levels, the degree of renal injury, and systemic lupus erythematosus disease activity index (SLEDAI) scores in patients with LN. Nrf2 protein levels were higher in the LN with high-eGFR group than in the healthy control and LN with low-eGFR groups. In follow-up patients in the LN high eGFR group, Nrf2 protein levels decreased significantly after remission of disease activity. Nrf2 protein expression has a dual role in patients with LN. Nrf2 protein levels not only correlate with disease activity in patients with LN, but also with the degree of kidney injury. Before implementing targeted therapy for Nrf2, evaluating both Nrf2 protein expression and the disease state in patients with LN is necessary to better identify and place each patient in an appropriate patient group.

Serum IgE anti-dsDNA autoantibodies in patients with proliferative lupus nephritis are associated with tubulointerstitial inflammation

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the overproduction of multiple autoantibodies. Lupus nephritis (LN), the most common cause of morbidity and mortality, requires early detection. However, only a limited number of serum biomarkers have been associated with the disease activity of LN. Serum IgE anti-dsDNA autoantibodies are prevalent in patients with SLE and may be associated with the pathogenesis of LN. In this study, serum samples from 88 patients with biopsy-proven proliferative LN were collected along with complete clinical and pathological data to investigate the clinical and pathological associations of anti-dsDNA IgE autoantibodies using ELISA. This study found that the prevalence of IgE anti-dsDNA autoantibodies in patients with proliferative LN was 38.6% (34/88). Patients with anti-dsDNA IgE autoantibodies were more prone to acute kidney injury (17/34 vs. 14/54; p = .025). Levels of anti-dsDNA IgE autoantibodies were associated with interstitial inflammation (r = 0.962, p = .017). Therefore, anti-dsDNA IgE autoantibody levels are associated with tubulointerstitial inflammation in patients with proliferative LN.

Serum S100P and C4d proteins as markers for active proliferative lupus nephritis in Egyptian patients with systemic lupus erythematosus

Lupus nephritis (LN), occurring in approximately 50% of individuals with systemic lupus erythematosus (SLE), significantly influences therapy and prognosis. Proliferative LN, more prevalent than non-proliferative LN, is associated with a poorer prognosis. This study aimed to investigate the potential correlation between serum levels of the pro-inflammatory proteins human calcium-binding S100P (S100P) and Human complement Fragment 4 (C4d) and confirmed proliferative LN through biopsy. The objective was to evaluate their reliability as biomarkers for disease activity in proliferative LN.
 Methods. Serum S100P and C4d were measured using enzyme-linked immunosorbent assay in 100 female patients with established SLE. Among these, 50 had confirmed proliferative LN through biopsy, and 50 did not. A control group of 50 healthy female donors' plasma samples was included.
 Results. SLE patients with proliferative LN exhibited significantly higher serum levels of S100P (P < 0.001) and C4d (P < 0.001) compared to SLE patients without LN and controls. Serum S100P demonstrated a significantly higher positive correlation with the activity index in renal biopsies (r = 0.784) compared to serum C4d (r = 0.416). Additionally, serum S100P had a significantly higher positive correlation with SLEDAI-R than serum C4d (r = 0.651 vs. r = 0.257). Both serum S100P and C4d showed promise as reliable biomarkers for the diagnosis of active proliferative LN, as indicated by the ROC curve and AUC assessments.
 Conclusion. Serum concentrations of S100P and C4d emerge as useful indicators for identifying SLE patients with active proliferative LN.

Angiopoietin-like 4 (ANGPTL4) Suppression Ameliorates Lupus Nephritis in MRL/lpr Mice by Inactivating NLRP3 Inflammasome and Inhibiting Inflammatory Response.

Lupus nephritis (LN) refers to the injury caused by systemic lupus erythematosus (SLE) involving the kidneys. A previous study identified angiopoietin-like protein 4 (ANGPTL4) as a novel urinary biomarker for tracking disease activity in LN. To investigate the detailed role and regulatory mechanism of ANGPTL4 in experimental models of LN. MRL/lpr mice 11-week-old were injected with adeno-associated virus (AAV)-mediated ANGPTL4 short hairpin RNA (shRNA). At 16 and 20 weeks of age, 24-h urine samples were harvested to measure proteinuria levels. After the mice were sacrificed, blood and kidney tissues were harvested to examine serum creatinine (cr) and blood urea nitrogen (BUN) levels, kidney histological changes, and pro-inflammatory cytokine production. Additionally, the levels of NLRP3 inflammasome-associated molecules in mouse renal tissues were detected to clarify the underlying mechanism. The AAV-sh-ANGPTL4 injection significantly reduced the proteinuria, cr, and BUN levels in MRL/lpr mice. ANGPTL4 silencing ameliorated glomerular, tubular, and interstitial damage in mice, mitigating the pathological alternations of LN. In addition, ANGPTL4 knockdown repressed pro-inflammatory cytokine production in the kidneys. Mechanically, ANGPTL4 suppression inhibited NLRP3 inflammasome expression in renal tissues of mice. ANGPTL4 silencing inhibits the NLRP3 inflammasome-mediated inflammatory response, thereby ameliorating LN in MRL/lpr mice.

Urine L-selectin reflects clinical and histological renal disease activity and treatment response in lupus nephritis across multi-ethnicity.

There is an urgent need for novel biomarkers in lupus nephritis (LN). We report a non-invasive urinary biomarker, L-selectin, in two independent multi-ethnic cohorts. uL-selectin was tested cross-sectionally in a Chinese cohort (n=255) and a US cohort (n=219) of SLE patients and controls using ELISA. A longitudinal cohort includes 20 active Chinese LN patients. uL-selectin was significantly increased in active LN patients compared to active non-renal SLE, inactive LN, inactive non-renal SLE, chronic kidney disease patients, and healthy controls. uL-selectin positively correlated with global and renal disease activities as well as histological activity index and chronicity index (CI). Low uL-selectin was an independent predictor for high CI. During follow-up, uL-selectin levels decreased significantly in the complete renal remission group. uL-selectin is a novel biomarker of disease activity and renal histopathology in LN across multiple ethnicities. It also reflects treatment response in LN patients during follow up.

A network-based approach reveals long non-coding RNAs associated with disease activity in lupus nephritis: key pathways for flare and potential biomarkers to be used as liquid biopsies.

A blood-based biomarker is needed to assess lupus nephritis (LN) disease activity, minimizing the need for invasive kidney biopsies. Long non-coding RNAs (lncRNAs) are known to regulate gene expression, appear to be stable in human plasma, and can serve as non-invasive biomarkers. Transcriptomic data of whole blood samples from 74 LN patients and 20 healthy subjects (HC) were analyzed to identify differentially expressed (DE) lncRNAs associated with quiescent disease and flares. Weighted gene co-expression network analysis (WGCNA) was performed to uncover lncRNAs with a central role (hub lncRNAs) in regulating key biological processes that drive LN disease activity. The association of hub lncRNAs with disease activity was validated using RT-qPCR on an independent cohort of 15 LN patients and 9 HC. cis- and trans-targets of validated lncRNAs were explored in silico to examine potential mechanisms of their action. There were 444 DE lncRNAs associated with quiescent disease and 6 DE lncRNAs associated with flares (FDR <0.05). WGCNA highlighted IFN signaling and B-cell activity/adaptive immunity as the most significant processes contributing to nephritis activity. Four disease-activity-associated lncRNAs, namely, NRIR, KLHDC7B-DT, MIR600HG, and FAM30A, were detected as hub genes and validated in an independent cohort. NRIR and KLHDC7B-DT emerged as potential key regulators of IFN-mediated processes. Network analysis suggests that FAM30A and MIR600HG are likely to play a central role in the regulation of B-cells in LN through cis-regulation effects and a competing endogenous RNA mechanism affecting immunoglobulin gene expression and the IFN-λ pathway. The expression of lncRNAs NRIR, KLHDC7B-DT, FAM30A, and MIR600HG were associated with disease activity and could be further explored as blood-based biomarkers and potential liquid biopsy on LN.

V-Set Immunoglobulin Domain-Containing Protein 4 as a Novel Serum Biomarker of Lupus Nephritis and Renal Pathology Activity.

To discover novel serum biomarkers that have diagnostic or predictive value in lupus nephritis (LN). Using a quantitative protein microarray, we screened for high-abundant proteome expression in the serum of patients with LN compared to healthy controls. Top candidates from this screening were validated using a larger cohort of patients with LN compared to a disease control cohort (subjects with other chronic kidney diseases) and a healthy control cohort. Promising markers were then selected using a machine-learning model and further validated with a larger patient cohort. The corresponding autoantibodies and immune complexes containing these proteins were also examined. In total, 13 proteins were found to be significantly elevated in LN patient serum in the screening, among which 8 proteins were validated by enzyme-linked immunosorbent assay using 81 serum samples from LN patients and control subjects. Three serum markers with LN diagnostic potential were identified using feature importance analysis and further validated using 155 serum samples from LN patients and control subjects. V-set immunoglobulin domain-containing protein 4 (VSIG4) appeared to be the most promising marker in distinguishing LN from healthy controls, with an area under the curve of 0.93. VSIG4 could also discriminate active LN from inactive LN. Furthermore, serum VSIG4 levels were positively correlated with all of the following clinical parameters: the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score (Spearman's rank correlation rs = 0.42, P < 0.001), the renal domain score of the SLEDAI (rs = 0.46, P < 0.001), the urinary protein-to-creatinine ratio (rs = 0.56, P < 0.001), and the serum creatinine level (rs = 0.41, P < 0.001). Importantly, we found that serum VSIG4 levels tracked with LN disease activity longitudinally, and that serum VSIG4 levels reflected the renal pathology activity index (AI), particularly the AI components of crescent formation and hyaline deposits. VSIG4 may be a promising novel serum biomarker and therapeutic target in patients with LN.

Renal interferon-inducible protein 16 expression is associated with disease activity and prognosis in lupus nephritis

BackgroundLupus nephritis (LN) is one of the most severe complications of systemic lupus erythematosus (SLE). However, the current management of LN remains unsatisfactory due to sneaky symptoms during early stages and lack of reliable predictors of disease progression.MethodsBioinformatics and machine learning algorithms were initially used to explore the potential biomarkers for LN development. Identified biomarker expression was evaluated by immunohistochemistry (IHC) and multiplex immunofluorescence (IF) in 104 LN patients, 12 diabetic kidney disease (DKD) patients, 12 minimal change disease (MCD) patients, 12 IgA nephropathy (IgAN) patients and 14 normal controls (NC). The association of biomarker expression with clinicopathologic indices and prognosis was analyzed. Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA) were utilized to explore potential mechanisms.ResultsInterferon-inducible protein 16 (IFI16) was identified as a potential biomarker for LN. IFI16 was highly expressed in the kidneys of LN patients compared to those with MCD, DKD, IgAN or NC. IFI16 co-localized with certain renal and inflammatory cells. Glomerular IFI16 expression was correlated with pathological activity indices of LN, while tubulointerstitial IFI16 expression was correlated with pathological chronicity indices. Renal IFI16 expression was positively associated with systemic lupus erythematosus disease activity index (SLEDAI) and serum creatinine while negatively related to baseline eGFR and serum complement C3. Additionally, higher IFI16 expression was closely related to poorer prognosis of LN patients. GSEA and GSVA suggested that IFI16 expression was involved in adaptive immune-related processes of LN.ConclusionRenal IFI16 expression is a potential biomarker for disease activity and clinical prognosis in LN patients. Renal IFI16 levels may be used to shed light on predicting the renal response and develop precise therapy for LN.

The Association of Urinary MCP-1 with Disease Activity of Lupus Nephritis

Background: The association of urinary MCP-1 (Monocyte Chemoattractant Protein-1) with disease activity in lupus nephritis (LN) has been a subject of significant interest. MCP-1 is a chemokine involved in the recruitment and activation of monocytes, which play a critical role in the pathogenesis of LN. Objective: To assess association of Urinary MCP-1 with disease activity of lupus nephritis. Method: This cross sectional study was conducted in the Department of Nephrology, Dhaka Medical College Hospital, Dhaka from January, 2017 to June, 2018. This cross sectional study was performed on 60 biopsy proven lupus nephritis patients and 30 age and sex matched apparently healthy control subjects. All the patients were recruited as per inclusion and exclusion criteria. Diagnosed SLE patients who had renal involvement and undergone renal biopsy for standard clinical indications were recruited by purposive sampling and divided into two groups of active and inactive LN as per operational definition. Results: During the study, The urinary MCP-1 was higher in active LN patients compared to the inactive group and both were higher than the level in the control. Plus, highest Sensitivity and specificity of uMCP-1 observed at cutoff value 433 pg/ml, where sensitivity was 0.967 and specificity was 0.900. Among 30 active lupus nephritis cases raised uMCP-1 was found in 29 cases and among 30 inactive lupus nephritis cases raised uMCP-1 was found in 3 cases. uMCP-1 showed very good agreement in diagnosis of lupus nephritis activity according to Kappa statistics. uMCP-1 in diagnosis of lupus nephritis activity showed accuracy, sensitivity, specificity, PPV and NPV were 0.933, 0.967, 0.900, 0.906 and 0.964 respectively. Conclusion: In conclusion, urinary MCP-1 holds great promise as a useful biomarker for the determination of lupus nephritis activity. Its association with disease activity, predictive value for treatment response and renal outcomes, and non-invasive nature make it an ...

Lupus Nephritis: New and Emerging Biologic and Targeted Therapies.

Lupus nephritis (LN) is a severe complication of systemic lupus erythematosus (SLE), a polyclonal systemic autoimmunity directed against nuclear and other self-antigens. SLE/LN affects mostly females during childbearing age, which puts them at risk for the progression of chronic kidney disease (CKD), cardiovascular disease, and pregnancy complications. The current management of LN involves the use of drugs with significant toxicities, and despite many attempts at novel drug interventions, the overall treatment efficacy has remained low. In this article, we discuss recent drug approvals and the upcoming pipeline of novel medications tested in clinical trials to improve effectiveness in terms of LN disease activity, LN relapse, and progression of LN-related CKD. In this context, we discuss (1) drugs with the potential to achieve these treatment goals by modulating SLE activity as the driving force for LN (e.g., belimumab, obinutuzumab, anifrolumab, and others); (2) drugs with SLE-non specific renoprotective effects by targeting non-immune mechanisms of LN progression (dapagliflozin, empagliflozin); and (3) drugs with dual immunosuppressive and antiproteinuric effects (voclosporin). Increasing the number of possible drug options will help to improve the management of LN in terms of efficacy and safety, and enable a more personalized treatment approach.

Efficacy of Mesenchymal Stem Cell Therapy on Lupus Nephritis and Renal Function in Systemic Lupus Erythematosus: A Meta-Analysis.

The purpose of this meta-analysis is to determine the efficacy of mesenchymal stromal/stem cell (MSC) transplantation therapy on lupus nephritis (LN) and renal function of patients with systemic lupus erythematosus (SLE). Articles that reported the data of MSC therapy on the renal function as well as disease activity of LN in patients with SLE were searched in PubMed, Web of Science, Embase and the Cochrane Library. Mean difference for disease activity and laboratory parameters were pooled to evaluate the efficacy of MSC, and incidence was pooled for clinical remission, death and severe adverse event. A total of 12 studies with 586 patients were included. The disease activity indices, including SLEDAI and BILAG, were significantly decreased within 12 months after MSC therapy (P< 0.05). Laboratory parameters for renal function and disease control including estimated glomerular filtration rate, creatinine, blood urea nitrogen, complement C3, albumin and urine protein, were also significantly improved after therapy. The pooled rate of clinical remission at 12 months was 28.1% and the total rate during follow-up was 33.7%. The pooled rate of death at 12 months was 5.2% and the total rate during follow-up was 5.5%. Severe adverse events were rare and not associated with the treatment of MSC. This is the first meta-analysis that focuses on the effect of MSC on LN and renal function of patients with SLE, and the results shows a favorable safety profile and encouraging results of MSC for improving the disease activity of LN as well as the renal function of SLE patients.

Peripheral Eosinophil Count Associated with Disease Activity and Clinical Outcomes in Hospitalized Patients with Lupus Nephritis

Introduction: The aim of this study was to evaluate the association of peripheral eosinophil (EOS) count with disease activity and kidney outcomes in lupus nephritis (LN) patients. Methods: A total of 453 hospitalized and biopsy-proven LN patients at our hospital from 2006 to 2013 were enrolled, of which 388 patients had repeated measurements of EOS. Relationships were explored between average EOS and disease activity at baseline, using the systemic lupus erythematosus disease activity (SLEDAI) and activity index (AI) on kidney biopsy. Follow-up data were available through December 2016. The primary outcome measure was a composite of doubling of serum creatinine and end-stage kidney disease after a median follow-up of 51 months. Results: The mean age of the enrolled 388 LN patients was 33.1 ± 10.8 years old, and 335 (86%) were female. The median average peripheral EOS count was 0.033 (0.015–0.057) ×10⁹/L. Mean AI and SLEDAI score were 6.8 ± 2.5 and 14.9 ± 5.4, respectively. Logistic regression models showed that decreased average EOS was independently associated with higher AI (≥6) and higher SLEDAI (≥15) (odds ratio [OR] 0.93, 95% confidence interval [CI] 0.90–0.97; and OR 0.96, 95% CI: 0.93–0.99, respectively). There was a parabolic relationship between average EOS and the primary outcome, with hazard ratio (HR) > 1 for both levels ≤0.033 and >0.16 × 10⁹/L. Conclusion: Lower EOS count was independently associated with severe disease activity and kidney progression in LN.

Renal NLRP3 Inflammasome activation is associated with disease activity in lupus nephritis

The current study was initiated to comprehensively evaluate renal NLRP3 inflammasome pathway activation in lupus nephritis (LN) patients and their clinicopathological significances based on a Chinese LN cohort. We found that the expressions of NLRP3, ASC, caspase-1, IL-1β and IL-18 were all significantly higher in the kidneys of LN patients and were predominantly expressed in glomerular mesangial cells, podocytes, renal tubular epithelial cells and macrophages. The expressions of NLRP3, ASC, caspase-1 and IL-1β were positively correlated to SLEDAI scores and several renal pathological activity indices, while the expression of NLRP3 was negatively associated with chronicity scores. Moreover, the foot process width was positively correlated with glomerular caspase-1 levels, and several podocyte injury markers were decreased significantly in LN patients with higher caspase-1 expression compared with those with lower expression. Our findings indicated that renal NLRP3 inflammasome was activated in LN patients and correlated with disease activity, which needs further explorations.

Real-world treatment utilization and economic implications of lupus nephritis disease activity in the United States.

BACKGROUND: Lupus nephritis (LN) is a common and severe complication of systemic lupus erythematosus (SLE), with approximately 40% of patients with SLE developing LN. Even with treatment, 10%-30% of patients will progress to end-stage renal disease (ESRD). Although many studies have assessed the clinical value of low disease activity in LN, the economic implications are less defined. OBJECTIVE: To evaluate treatment utilization and health care costs associated with active disease, low disease activity, and ESRD in patients with LN. METHODS: A retrospective analysis of Optum pharmacy and medical claims data from 2015 to 2019 was performed and included patients with a diagnosis of SLE (International Classification of Diseases, Ninth Revision or Tenth Revision codes 710.0 or M32, respectively) and additional prespecified criteria for LN. Total health care payer costs for medical and pharmacy services and treatment utilization for commonly prescribed medications were determined for periods of low disease activity, active disease, or ESRD. RESULTS: A total of 21,251 patients (mean age 60.3 years; 87% female; 55% White patients and 18% Black patients) with a mean follow-up period of 30.6 months were included; the majority of patients had active disease (67.3%), followed by low disease activity (51.3%), and ESRD (10.5%). Glucocorticoids were used 2 times more often and mycophenolate mofetil was used 4 times more often in patients with active disease vs low disease activity. Glucocorticoids, mycophenolate mofetil, and tacrolimus were more commonly used in patients with ESRD vs those with low disease activity. Mean medical costs were $4,777 per month in active disease and $18,084 per month in ESRD vs $2,523 per month in low disease activity. CONCLUSIONS: Treatment burden and costs are high for patients with active disease and ESRD in LN. Treatments that allow patients to achieve and maintain low disease activity may help improve patient outcomes and reduce medication use and overall health care costs. DISCLOSURES: Maria Dall'Era and Kenneth Kalunian are consultants of Aurinia Pharmaceuticals. Eric Turowski, Vanessa Birardi, Neil Solomons, Simrat Randhawa, and Paola Mina-Osorio are employees and stockholders of Aurinia Pharmaceuticals. Michael Eaddy is a former employee of Xcenda, LLC. Augustina Ogbonnaya and Eileen Farrelly are employees of Xcenda, LLC, which was contracted by Aurinia Pharmaceuticals to assist in the conduct of this study and the writing of this manuscript. Aurinia Pharmaceuticals provided funding for this study and the preparation of the manuscript. Aurinia Pharmaceuticals had a role in writing the report and decision to submit for publication.

Serum cystatin C and βeta-2 microglobulin as potential biomarkers in children with lupus nephritis.

In this study, we aimed to assess serum levels of Cystatin C (Cys C) and beta-2 microglobulin (β2M) in juvenile systemic lupus erythematosus (JSLE) patients and to investigate their role as potential biomarkers of lupus nephritis (LN) and overall disease activity. Between December 2018 and November 2019, a total of 40 patients with JSLE (11 males, 29 females; mean age: 12.6±2.5 years; range, 7.5 to 16 years) and 40 age- and sex-matched controls (10 males, 30 females; mean age: 12.3±2.4 years; range, 7 to 16 years) were included in this study. Serum (s) Cys C and β2M levels were compared between the groups. The SLE Disease Activity Index (SLEDAI-2K), the renal SLEDAI (rSLEDAI), and the Renal Damage Index were used. JSLE patients had significantly elevated mean sCyc C and sβ2M levels (1.4±0.8 mg/mL and 2.8±0.9 mg/mL, respectively) compared to the controls (0.6±0.1 mg/mL and 2.0±0.2 mg/mL, respectively; p<0.00). The mean sCys C and sβ2M levels were significantly higher in the LN group, compared to non-LN patients (1.8±0.7 mg/mL and 3.1±1.0 mg/mL, respectively vs. 0.8±0.3 mg/mL and 2.4±0.6 mg/mL, respectively; p=0.002 and p=0.02, respectively). The sCys C levels had significant positive correlations with erythrocyte sedimentation rate (r=0.3, p=0.05), serum creatinine (r=0.41, p= 0.007), 24-h urinary protein (r=0.58, p<0.001), anti-double stranded deoxyribonucleic acid antibodies titers (r=0.55, p=0.002), extra-renal SLEDAI scores (r=0.36, p=0.04), rSLEDAI (r=0.46, p=0.002), and renal class (r=0.7, p=0.0001). Serum β2M levels were significantly negatively correlated with complement 4 levels (r=-0.31, p=0.04) and significantly positively correlated with extra-renal SLEDAI scores (r=0.3, p=0.05). These findings confirm that sCys C and sβ2M levels are increased in JSLE patients in association with the overall active disease. However, sCys C level may act as a promising non-invasive biomarker for predicting kidney disease activity and biopsy classes in children with JSLE.