Defining PI3K Signaling as a Key Regulator of Molecular Heterogeneity and Inflammation in Glomerular Lupus Nephritis.

Nonstandard and adjunctive medical therapies for systemic lupus erythematosus

POS1430 EPIDEMIOLOGY OF LUPUS NEPHRITIS IN BRAZIL: FINDINGS FROM THE MACUNAÍMA STUDY - A NATIONWIDE MULTICENTRIC STUDY

BackgroundCognitive dysfunction (CD) is among the most frequent neuropsychiatric manifestation of systemic lupus erythematosus (SLE) that has a considerable impact on quality of life, but still lacks adequate screening in...

Lupus nephritis (LN) is a major manifestation of systemic lupus erythematosus (SLE). It remains unclear whether antiphospholipid antibodies (aPL) alter the course of LN. We thus investigated the impact of aPL on short-term and long-term renal outcomes in patients with LN. We assessed levels of aPL cross-sectionally in SLE patients diagnosed with (n = 204) or without (n = 294) LN, and prospectively in 64 patients with active biopsy-proven LN (52 proliferative, 12 membranous), before and after induction treatment (short-term outcomes). Long-term renal outcome in the prospective LN cohort was determined by the estimated glomerular filtration rate (eGFR) and the Chronic Kidney Disease (CKD) stage, after a median follow-up of 11.3 years (range: 3.3–18.8). Cross-sectional analysis revealed no association between LN and IgG/IgM anticardiolipin or anti-β2-glycoprotein I antibodies, or lupus anticoagulant. Both aPL positivity and levels were similar in patients with active LN and non-renal SLE. Following induction treatment for LN, serum IgG/IgM aPL levels decreased in responders (p<0.005 for all), but not in non-responders. Both at active LN and post-treatment, patients with IgG, but not IgM, aPL had higher creatinine levels compared with patients without IgG aPL. Neither aPL positivity nor levels were associated with changes in eGFR from either baseline or post-treatment through long-term follow-up. Moreover, aPL positivity and levels both at baseline and post-treatment were similar in patients with a CKD stage ≥3 versus 1–2 at the last follow-up. In conclusion, neither aPL positivity nor levels were found to be associated with the occurrence of LN in SLE patients. However, IgG aPL positivity in LN patients was associated with a short-term impairment of the renal function while no effect on long-term renal outcome was observed. Furthermore, IgG and IgM aPL levels decreased following induction treatment only in responders, indicating that aPL levels are affected by immunosuppressive drugs in a response-dependent manner.

PSY29 CHARACTERISTICS AND DISEASE MANAGEMENT IN A LARGE REAL WORLD LUPUS NEPHRITIS COHORT IN THE US

Lupus nephritis (LN) is a common manifestation of systemic lupus erythematosus (SLE) that can lead to irreversible renal impairment. Lupus nephritis is initiated by the deposition of nucleic acid-containing material...

Systemic lupus erythematosus (SLE) is a life-long, life-limiting and multi-systemic autoimmune disease. Glomerulonephritis is one of the most serious manifestations of SLE. Younger children have an increased incidence, severity and morbidity of lupus nephritis (LN) compared with adult-onset disease. Monocyte chemoattractant protein-1 (MCP-1) enhances leukocyte adhesiveness and endothelial permeability in the kidneys of murine and human LN models. Our study aimed to assess the role of urinary MCP-1 in the early diagnosis of LN activity. Sixty children, of whom 45 children aged from six to 12 years old and of both sexes (15 SLE patients without nephritis, 15 active LN and 15 inactive LN) fulfilling the American College of Rheumatology Classification Criteria for SLE were studied in comparison with 15 healthy subjects. We investigated the serum and urinary MCP-1 in all groups using the enzyme-linked immunosorbent assay test. Urinary MCP-1 was significantly higher in active LN in comparison with inactive LN and controls, and also significantly higher in inactive LN in comparison with SLE without nephritis and controls. There was also a significant difference between SLE without nephritis and controls. Serum MCP-1 was significantly higher in the group with active LN in comparison with the inactive group and SLE without nephritis and controls, but there was no significant difference between SLE and controls. The urinary MCP-1 level correlated well with SLE disease activity as measured by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Urinary MCP-1 correlates positively with proteinuria, blood urea nitrogen level and creatinine and negatively with hemoglobin and creatinine clearance. We concluded that measurement of MCP-1 in urine may be useful for monitoring the severity of renal involvement in SLE. We recommend measuring urinary MCP-1 in pediatric SLE for the early diagnosis of LN and for the evaluation of the severity of renal involvement.

Lupus nephritis (LN) remains one of the most severe manifestations in patients with systemic lupus erythematosus (SLE). Onset and overall LN risk among SLE patients remains considerably difficult to predict. Utilizing a territory-wide longitudinal cohort of over 10 years serial follow-up data, we developed and validated a risk stratification strategy to predict LN risk among Chinese SLE patients - Risk and Factors associated with disease manifestations in systemic Lupus Erythematosus - Lupus Nephritis (RIFLE-LN). Demographic and longitudinal data including autoantibody profiles, clinical manifestations, major organ involvement, LN biopsy results and outcomes were documented. Association analysis was performed to identify factors associated with LN. Regression modelling was used to develop a prediction model for 10-year risk of LN and thereafter validated. A total of 1652 patients were recruited: 1382 patients were assigned for training and validation of the RIFLE-LN model; while 270 were assigned for testing. The median follow-up duration was 21 years. In the training and validation cohort, 845 (61%) of SLE patients developed LN. Cox regression and log rank test showed significant positive association between male sex, age of SLE onset and anti-dsDNA positivity. These factors were thereafter used to develop RIFLE-LN. The algorithm was tested in 270 independent patients and showed good performance (AUC = 0·70). By using male sex, anti-dsDNA positivity, age of SLE onset and SLE duration; RIFLE-LN can predict LN among Chinese SLE patients with good performance. We advocate its potential utility in guiding clinical management and disease monitoring. Further validation studies in independent cohorts are required.

Studies have demonstrated that male systemic lupus erythematosus (SLE) patients present with atypical manifestations, serious kidney involvement and worse prognosis. This article summarizes the findings obtained from the literature review of 16 studies to obtain an understanding of the gender correlation with SLE and lupus nephritis. We compared the influence of gender on various factors of SLE like incidence of lupus nephritis, age at manifestation of SLE, time between SLE manifestation and lupus nephritis diagnosis, frequency of dialysis, mortality risk and biopsy findings. Studies included in our review composed of remote published work, case-control studies, case reports and cross-sectional studies. Of 16 studies, 14 were conducted exclusively on lupus nephritis in SLE with comparison of gender correlation and remaining 2 studied SLE generally without any gender comparison. Six studies pointed to an increase in incidence of lupus nephritis in males, 9 studies demonstrated no disparity in gender, and one study showed contradicting results. In addition, 4 studies pointed that males had a more severe renal outcome as revealed by laboratory tests. Interestingly the age at which SLE manifests was the same in both genders according to 2 studies. Moreover, the frequency of dialysis and remission were similar between both genders. There is no consensus if these atypical manifestations are more common in males. Although some studies do show a significant increase in lupus nephritis among male SLE patients, others showed no difference or contradicting results. Hence, we suggest further studies comparing the disease manifestations.

Background:Systemic Lupus Erythematosus (SLE) renal involvement occurs in approximately 40-50% of adult patients. Compared to adult-onset SLE cases, pediatric-onset SLE nephritis is reported to be more prevalent and often results...

Lupus nephritis (LN) is the main manifestation of systemic Lupus Erythematosus (SLE). MicroRNAs (miRNAs) and autoantibodies could be suitable candidate biomarkers of LN. This study evaluates the expression of circulating miR-148a and miR-126 along with anti-dsDNA, anti-C1q, and anti-C3b autoantibodies in SLE patients with LN (SLE + LN). 30 women with SLE, 30 women with SLE + LN, and 25 women as healthy controls (HCs) were enrolled in this study. The plasma expression of selected miRNAs was evaluated by real-time PCR. The serum level of anti-dsDNA, C1q, and C3b antibodies was measured by the ELISA. The expression of miR-148a was significantly increased in SLE and SLE+LN groups compared with the control group. No significant difference was found in the expression of miR-126 among the groups. The frequency of autoantibodies was significantly higher in the SLE + LN group than SLE. The Higher levels of circulating miR-148a in the SLE samples compared with the HCs suggest that this miRNA could be a reliable biomarker for SLE patients (with or without LN). Also, autoantibodies against dsDNA, C1q, and, C3 could be used for the prediction of SLE nephritis, independently. However, further studies are needed to confirm these findings.

THU0352 Risk of Status Epilepticus and Intractable Epilepsy in Systemic Lupus Erythematosus Patients with Lupus Nephritis

Background and Aims Systemic lupus erythematosus (SLE) often affects the kidneys, and is associated with morbidity and mortality. Ethnic variations in clinical response to treatment and outcomes have been described. Information on real-life, long-term cohorts of the Middle Eastern Israeli population is lacking. We aimed to characterize the prevalence and long-term outcomes of kidney involvement in SLE patients in Israel and to identify variables associated with lupus nephritis (LN) and end-stage kidney disease (ESKD). Method This retrospective study, conducted between 2014-2023, included adult patients with SLE diagnosed for at least 12 months. Kidney involvement was based on a diagnosis of LN on a kidney biopsy. SLE patients without LN served as controls. Associated variables were collected including socio-demographics, disease-related characteristics, kidney-related factors, comorbidities, and all-cause mortality. Results A total of 182 adult patients with SLE were included. Of them, 54 (29.6%) had LN. Mean follow-up since diagnosis was 16.2 ± 13.8 years. Compared to the control group, patients with LN were diagnosed with SLE at younger ages (26.8 ± 12.9 vs. 35.5 ± 15.4 years, p &amp;lt; 0.01). Patients with LN and controls had similar proportions of females/males and Jewish/Arab patients (Table 1), and had comparable baseline eGFR before LN diagnosis (110 ± 48 vs. 107 ± 39 ml/min/m2, p = 0.66). The LN group had lower complement C3 levels at diagnosis and higher dsDNA titers (p = 0.001, 0.023 respectively; Table 1). Patients with LN had more hospitalization for SLE exacerbations [38.4% vs. 24.5%, odds ratio (OR) 1.9, 95% confidence interval (CI) 1-3.9, p = 0.06]. Of 54 patients with LN, 45 had available treatment information. All patients were treated with hydroxychloroquine, 19 patients (42.2%) were treated with cyclophosphamide, and 36 (80%) were treated with mycophenolate mofetil or mycophenolic acid. During follow-up of the LN patients, 5 patients (9.3%) were diagnosed with diabetes, 21 patients (38.9%) were diagnosed with hypertension, 5 patients (9.3%) had a stroke and 6 patients (11.1%) had an acute coronary syndrome. Eight of the LN patients (14.8%) developed ESKD as compared with one patient (0.8%) of the controls (OR 22.1, 95% CI 2.7-181.5, p &amp;lt; 0.001). On univariate analysis, ESKD was significantly associated with LN, hypertension, heart failure, and non-employment status. No difference in the rate of ESKD was found between Jewish and Arab patients. On multivariate regression analysis, LN and hypertension were the most important predictors for developing ESKD. Mortality among patients with ESKD was 22% vs. 4.6% among non-ESKD patients (p = 0.02) )Fig. 1). Conclusion This long-term study on Israeli SLE patients reveals that despite advances in SLE treatments, LN is associated with significant morbidity and mortality. The elevated risk of ESKD, particularly associated with LN and hypertension, underscores the imperative for targeted interventions to improve outcomes.

Background: Lupus nephritis (LN) is an inflammation of the kidneys that is related to systemic lupus erythematosus (SLE). This study aimed to evaluate the differences in clinical and laboratory characteristics between LN and non-LN SLE patients. Methods: We conducted a retrospective analysis of medical records collected from SLE patients treated at the University Hospital in Kraków, Poland, from 2012 to 2022. All patients met the 2019 European League Against Rheumatism and the American College of Rheumatology (EULAR/ACR) criteria for SLE. Results: Among 921 SLE patients, LN was documented in 331 (35.94%). LN patients were younger at SLE diagnosis (29 vs. 37 years; p < 0.001) and had a male proportion that was 2.09 times higher than the non-LN group (16.62% vs. 7.97%; p < 0.001). They were more often diagnosed with serositis and hematological or neurological involvement (p < 0.001 for all). Hypertension and hypercholesterolemia occurred more frequently in these patients (p < 0.001 for both). LN patients exhibited a higher frequency of anti-dsDNA, anti-histone, and anti-nucleosome antibodies (p < 0.001 for all). Conversely, the non-LN group had a 1.24-fold (95% CI: 1.03-1.50; p = 0.021) increase in the odds ratio of having positive anti-cardiolipin IgM antibody results. LN patients were more frequently treated with immunosuppressants. The risk factors for experiencing at least three LN flares included female sex, younger age at the onset of LN or SLE, LN occurring later than SLE onset, the presence of anti-nucleosome or anti-dsDNA antibodies, and certain SLE manifestations such as myalgia, arthritis, proteinuria > 3.5 g/day, and pathological urinary casts in the urine sediment. Conclusions: LN patients differ from non-LN patients in the age of SLE diagnosis, treatment modalities, and autoantibody profile and have more frequent, severe manifestations of SLE. However, we still need more prospective studies to understand the diversity of LN and its progression in SLE patients.

Background/Objectives: Lupus nephritis (LN) is one of the most severe organ manifestations of systemic lupus erythematosus (SLE). Chronic kidney disease (CKD) and its progression into end-stage renal disease (ESRD) are serious complications in LN and the main cause of death in SLE. We aimed to investigate the prognostic factors of the progression of CKD and the development of ESRD in SLE patients. Methods: In our retrospective cohort study, we assessed the clinical and laboratory data of 127 patients who were diagnosed with LN between 1990 and 2022 and received regular follow-up care at our autoimmune centre. We compared class IV (diffuse) LN patients with non-class IV LN patients and assessed the differences in clinical and laboratory data of the patients, subdivided into complete, partial, and non-responders to therapy. Results: The prevalence of class IV LN is significantly higher in patients with CKD stage 3-5. Age above 42, class IV LN, Coombs positivity, and high chronicity index are prognostic factors for the development of CKD stage 3-5. On the other hand, anti-RNP and anti-SS-B antibody positivity and a high chronicity index are prognostic factors for the development of ESRD. The chronicity index, as well as the SLICC/ACR Damage Index (SDI) score, was significantly higher in non-responders compared to patients with complete remission. Conclusions: Based on our results, the progression of CKD into stage 3-5 or the development of ESRD should be expected at a chronicity index above 3.5 points. An early diagnosis, as well as aggressive, timely, and adequate treatment, is fundamental to prevent unfavourable outcomes of LN.