Onset Of Lupus Nephritis Research Articles

Comparison of Clinical and Laboratory Characteristics in Lupus Nephritis vs. Non-Lupus Nephritis Patients-A Comprehensive Retrospective Analysis Based on 921 Patients.

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.

Pregnancy outcomes and risk factors analysis in patients with systemic lupus erythematous

BackgroundThe management of systemic lupus erythematosus (SLE) during pregnancy remains a challenge currently. Identifying early predictors of adverse pregnancy outcomes in SLE patients can help to develop treatment plan and improve prognosis. The aim of this study is to explore the clinical and laboratory variables in the early pregnancy that can predict adverse neonatal and maternal outcomes, thereby facilitating the grading management of SLE.MethodsA retrospective analysis was conducted on 126 pregnant women with SLE who were admitted to Zhongnan Hospital of Wuhan University between January 2017 and December 2022. All enrolled patients were diagnosed (including newly diagnosed and previously diagnosed) during first trimester of pregnancy and their clinical records, laboratory results and pregnancy outcomes were reviewed. The association between the clinical and laboratory characteristics of patients at 12 gestational age and the adverse neonatal (ANOs) as well as maternal outcomes (AMOs) were analyzed.ResultsA total of 117 live births (92.8%) were recorded in the study. ANOs occurred in 59 (46.8%) cases, including fetal loss in 9 cases (7.1%), preterm birth in 40 cases (31.7%), small for gestational (SGA) in 15 cases (11.9%), and complete heart block in 2 cases (1.5%). Univariate analysis showed that disease activity index (P < 0.0001), lupus nephritis (P = 0.0195), anti-SSB positivity (P = 0.0074) and hypocomplementemia (P = 0.0466) were related to ANOs. However, multivariate analysis showed that only disease activity during early pregnancy was an independent predictor for ANOs (OR = 7.053, 95% CI: 1.882 to 26.291, P = 0.004). In addition, 48 patients experienced AMOs during subsequent trimester, including 24 (19.0%) patients with disease flare and 23 (18.3%) patients with pre-eclampsia. Unplanned pregnancy (P = 0.010), active disease (P = 0.0004), new onset SLE (P = 0.0044) and lupus nephritis (P = 0.0009) were associated with AMOs in univariate analysis, while disease activity was identified as an independent risk factor for AMOs (OR = 2.553, 95% CI: 1.012–6.440, P = 0.047).ConclusionActive disease in early pregnancy is associated with adverse pregnancy outcomes. For patients with high risk factor for ANOs and AMOs, more intensive treatment and follow-up should be a wise measure. Especially for those who suffer from active disease, they should be fully informed and given the option to terminate or continue their pregnancy.

#896 Long-term renal outcome in childhood-onset lupus nephritis

Abstract Background and Aims Lupus nephritis (LN) is a common and severe complication of childhood-onset SLE. Little is known about the long-term renal outcome of childhood-onset LN. We investigated predictive factors of end-stage kidney disease (ESKD) and chronic kidney disease (CKD) in a paediatric cohort of patients with LN. Method This is a retrospective multicentre study including patients with childhood-onset (&amp;lt;18 years) biopsy-proven LN. Clinical features were analysed at disease onset, time of kidney biopsy, 12 and 24 months after biopsy, and last follow-up. We investigated the prognostic significance of clinical, laboratory and histologic characteristics on the incidence of ESKD and CKD stage 3-5. Results We included 73 patients with a median age of 14 years (IQR 11.5-17) . At the time of kidney biopsy, most subjects displayed an aggressive disease: 2 (3%) children required haemodialysis, 27 (38%) had an estimated glomerular filtration rate (eGFR) &amp;lt;60 mL/min/1.73 m2. The overall median eGFR was 70 mL/min/1.73 m2 (IQR 43-96) . Moreover, the median proteinuria was 4 g/24 h (IQR 1.35-7.41) , with 41 (59%) children displaying a nephrotic range proteinuria (i.e., &amp;gt;3 g/24 h) . The median follow-up was 13.3 years (IQR 4.7-25.4) . A total of 10 patients (13.7%) reached ESKD, the majority of whom (12%) within 10 years from kidney biopsy; during the subsequent follow-up the incidence of ESKD stabilised (Fig. 1). At last follow-up, around 50% of patients displayed an eGFR &amp;lt;90 mL/min/1.73 m2. A younger age at LN onset, a lower eGFR and central nervous system involvement at the time of kidney biopsy were identified as predictors of ESKD by a univariable Cox regression model (Table 1). The same features were significantly associated with the occurrence of CKD stage 3-5 at last follow-up at a univariable logistic regression analysis. Conclusion LN often presents with severe kidney function impairment and aggressive systemic involvement in children. In our cohort, whose follow-up was among the longest reported in the literature, 12% of patients reached ESKD within 10 years from kidney biopsy. Significant predictors of poor kidney outcome in the long term were a younger age at LN onset, a lower eGFR and the presence of neurological manifestations at the time of kidney biopsy.

#1505 Late-onset lupus nephritis: clinical-epidemiological, histological, prognostic and therapeutical implications: a single center experience

Abstract Background and Aims Systemic lupus erythematosus (SLE), a chronic autoimmune disease, and lupus nephritis (LN), are typically diagnosed in women in fertile age. Late-onset SLE is defined as a disease onset over 50 years. Our main objective was to analyze the clinical, histological, prognostic and therapeutical features related to LN in our late-onset SLE population. Method A single center and retrospective study was performed comparing clinical-demographic, histological, prognostic and therapeutical data of 45 LN biopsied patients from 1994 to 2023. We divided the study population according to the age of onset of LN into classic-onset (&amp;lt; 45 years) and late-onset (&amp;gt; 45 years). Results Late-onset LN patients showed a higher association with Sjögren's and antiphospholipid syndrome, more cardiovascular comorbidities at presentation, poorer renal function at diagnosis and higher SDI score. On histology they showed more non-proliferative LN classes (II followed by V). Late-onset LN responders needed more time to achieve response but had fewer relapses. Non responsive patients had more incidence of acute kidney injury (AKI) and more glomerulosclerosis and interstitial fibrosis-tubular atrophy (IFTA) at presentation, as well as more need for renal replacement therapy (RRT) at diagnosis and at follow-up. The principal independent variables associated with relapse were the younger age at SLE diagnosis and an initial partial renal response (PRR). Patients of both groups who experienced relapse received higher doses of intravenous cyclophosphamide and less mycophenolic acid (MFA) analogues. Patients who received induction with MFA analogues were more likely to achieve complete renal response (CRR) or non-renal response (NRR). Conclusion late-onset LN is often accompanied by poor renal function at presentation. It seems imperative to establish a tailored approach in this fragile population in order to avoid unnecessary immunosuppression.

#1602 Lupus nephritis multidisciplinary consultation: a new strategy for increasingly complex patients

Abstract Background and Aims Lupus nephritis (LN) is a major course of morbidity and mortality in patients with systemic lupus erythematosus (SLE), best managed by a multidisciplinary group. Recent management advances require greater collaboration between specialists and individualized treatments in severe cases. Method We conducted a retrospective, single-center study of a cohort of incident patients which were diagnosed with LN between 2015 and 2022 and began follow-up in the multidisciplinary rheumatology and nephrology consultation of our institution. Clinical and analytical characteristics at diagnosis and during follow-up were studied. The primary endpoint was complete remission rate at follow-up end, according to GLOSEN (Grupo de Estudio de Enfermedades Glomerulares de la SEN) [1] criteria. Changes in immunosuppression schemes over time were studied. Results 26 patients (92.3% women) were included. Median age at SLE diagnosis was 30.5 years [Interquartile range (IQR) 23.7 – 44.2]. Most patients were Hispanic (14 patients, 53.8%). Median time between SLE and LN diagnosis was 21 months (IQR 0-129 months). In 9 patients (34.6%), SLE and LN onset happened simultaneously. Most common renal manifestation was hematuria, which appeared in 19 patients (73.1%). Median proteinuria was 1.83 g/d (IQR 0.88-2.92) and serum creatinine level, 0.69 (IQR 0.51-1.18). Hypocomplementemia (88.5%) and positivity to anti-DNA (69.2%) were common. Most frequent classes found in renal biopsies were IV (30.8%) and V (23.1%). At LN debut, SLEDAI score, which assesses SLE manifestations, had a median value of 16 (IQR 12-20). Mycophenolate mofetil (96.2%) was the main induction agent. Intravenous steroids were administered in 14 patients (53.8%) and the rest received steroids at a dose of 0.5 mg/kg/day. Addition of another therapy, mainly tacrolimus (6 patients, 23.1%) and belimumab (4 patients, 15.4%), was needed to achieve remission in 12 patients (46.2%). In 8 of them (66.6%), treatments were added within the first 6 months. These 12 patients had less chronicity in the biopsy (median chronicity index: 0 vs. 2; p 0.004) and had higher proteinuria (median 1.41 g/day vs. 0.4 g/day; p 0.001). Likewise, SLEDAI score at 3 months was significantly higher in these 12 patients than in the standard of care group (median SLEDAI score 13 vs. 8; p 0.016). No differences were found in 3 month serum creatinine (p 0.181) or 3 month hematuria (p 0.496) After a median follow-up of 47 months, 15 (57.7%) and 9 patients (34.6%) achieved complete and partial remission, respectively. No differences in percentages of remission were observed between the 2 groups. Steroids were withdrawn in 12 patients (46.2%). Median steroid dose at the end of follow-up was 5 mg (IQR 3-5). Conclusion In our LN cohort, higher SLEDAI and proteinuria indicated the need for an individualized approach. Collaboration between Rheumatology and Nephrology specialists is essential to identify patients with these needs.

#1133 Kidney characteristics of belimumab-treated patients with SLE pre-lupus nephritis indication: identifying data for future comparative research

Abstract Background and Aims Lupus nephritis (LN) is a severe, renal manifestation occurring in approximately 40% of patients with the chronic autoimmune disease systemic lupus erythematosus (SLE) [1]. Belimumab (BEL), a human immunoglobulin G1λ monoclonal antibody that binds to and inhibits soluble B-lymphocyte stimulator, was indicated for SLE in 2011 and LN in 2020 by the US Food and Drug Administration [2]. BEL has proven efficacy for SLE and LN [2], but there are limited data regarding the effectiveness of BEL to delay LN onset due to lack of sufficient follow-up time. Evaluating the demographic, clinical and kidney characteristics of patients treated with BEL before its regulatory approval for LN allows for a longer follow-up period. This study describes the kidney characteristics of patients with SLE treated with BEL and/or standard therapy (ST) pre-LN indication. The objective was to evaluate whether there are sufficient data from BEL-treated patients with kidney impairment and available laboratory measurements for use in future comparative research regarding effectiveness of BEL to delay LN onset. Method This retrospective, real-world study (GSK Study 217532) used electronic health record (EHR) data to assess adult patients with SLE. Eligible patients received BEL with or without ST (BEL cohort) or ST only (ST cohort) during the study identification period (1 January 2017 to 31 December 2020) and had activity in the EHR 12 months pre-index (baseline period); the index date was the first prescription of BEL or ST. A diagnosis of SLE was defined as presence of International Classification of Diseases, 10th Revision, Clinical Modification codes (M32.1x, M32.8, M32.9) based on either ≥ 2 outpatient medical claims or ≥ 1 inpatient/emergency department claim during the baseline period (or index date). Patients were excluded if they received BEL during the baseline period. LN- and kidney-related characteristics were measured during the baseline period and after 36 months of follow-up. Results This study identified 32 017 patients with SLE: 1318 in the BEL cohort and 30 699 in the ST cohort. The mean (standard deviation) age of the BEL and ST cohorts was 43.9 (12.7) and 51.9 (15.2) years, respectively. Most patients were White (BEL: n = 804 [61.0%]; ST: n = 19,812 [64.5%]) and female (BEL: n = 1247 [94.6%], ST: n = 27 826 [90.6%]). At baseline, 13.1% of the BEL cohort and 10.0% of the ST cohort had an LN diagnosis; chronic kidney disease (CKD) was reported in 22.1% of the BEL cohort and 27.7% of the ST cohort (Table 1). End-stage kidney disease (ESKD) was observed at baseline in 1.0% of the BEL cohort and 4.0% of the ST cohort. Dialysis rate at baseline was 0.7% in the BEL cohort and 3.5% in the ST cohort. A smaller proportion of the BEL cohort had kidney impairment than the ST cohort. Overall, 32.1% of the BEL cohort (n = 423) and 46.1% of the ST cohort (n = 14,162) had 36 months of valid follow-up. The proportion of patients with available kidney laboratory characteristics was generally similar between baseline and 36 months follow-up, and between BEL and ST cohorts (Table 2). However, the proportion of the BEL cohort at baseline and at 36 months’ follow-up with a proteinuria laboratory measurement was &amp;gt;2-fold that of the ST cohort (baseline: BEL = 30.5%, ST = 12.9%; follow-up: BEL = 42.1%, ST = 20.2%). Conclusion This study demonstrates that there are adequate kidney value measurements for BEL and ST patients available to assess kidney outcomes over time in patients with SLE pre-LN indication of BEL. Observationally, the ST cohort displayed more impairment than the BEL cohort, which could indicate more advanced disease in this slightly older cohort. However, future studies should account for baseline differences between ST and BEL cohorts to assess kidney impairment–related outcome measures, by using matching and weighting procedures. Funding GSK.

Treatment with lysophosphatidic acid improves glomerulonephritis through the suppression of macrophage activation in a murine model of systemic lupus erythematosus.

Several therapeutic agents have been developed and used for the clinical treatment of systemic lupus erythematosus (SLE). In cases where SLE is accompanied by severe organ failures, such as neuropsychiatric lupus erythematosus (NPSLE) and acute onset of lupus nephritis, the use of potent immunosuppressive drugs, such as cyclophosphamide, is necessary. However, potent immunosuppressive drugs are known to increase infection risks. Thus, the development of therapeutic agents with novel mechanisms is urgently required. Previously, we reported that treatment with lysophosphatidic acid (LPA) prevents depression-like behaviours by suppressing microglial activation in MRL/lpr mice. In this study, we examined whether the treatment with LPA improves glomerulonephritis by affecting systemic immunity in MRL/lpr mice. Eighteen-week-old MRL/lpr mice were treated with a vehicle or LPA for 3 weeks. After treatment, the glomerular inflammation and damage parameters were compared between the 2 groups. Moreover, we examined the effects of LPA on immune cells by flow cytometry using isolated splenocytes. LPA treatment in MRL/lpr mice significantly reduced the daily urinary albumin content and suppressed the CD68-positive cells and Periodic acid-Schiff (PAS)-positive areas in the glomeruli. The treatment also suppressed plasma anti-dsDNA antibodies and inflammatory cytokines in MRL/lpr mice. Although LPA did not significantly affect the total number of splenocytes, the treatment significantly reduced CD11b+Ly6G-Ly6C- cells (mature macrophages), as well as CD11b+Ly6G-Ly6C-CD68+ cells (activated mature macrophages). These results suggest that LPA may improve glomerulonephritis by suppressing macrophage activation in MRL/lpr mice.

Novel mitophagy inducer alleviates lupus nephritis by reducing myeloid cell activation and autoantigen presentation

Lupus nephritis (LN) is one of the most severe manifestations of systemic lupus erythematosus (SLE), but its mechanism of onset remains unclear. Since impaired mitophagy has been implicated in multiple organs in SLE, we hypothesized that mitophagy dysfunction is critical in the development of LN and that pharmacologically targeting mitophagy would ameliorate this disease. Therefore, lupus-prone MRL/MpJ-Faslpr (MRL/lpr) and NZBWF1/J mice were treated with a novel mitophagy inducer, UMI-77, during their onset of LN. This treatment effectively mitigated kidney inflammation and damage as assessed by histology and flow cytometry. Furthermore, dendritic cell (DC)-T cell coculture assay indicated that UMI-77 treatment attenuated DC function that would drive T cell proliferation but did not directly influence the potent T cell proliferation in lupus mice. UMI-77 also restored mitochondrial function and attenuated proinflammatory phenotypes in lupus DCs. Adoptive transfer of DCs from MRL/lpr mice augmented serum anti-dsDNA IgG, urine protein and T cell infiltration of the kidney in MRL/MpJ mice, which could be prevented by either treating lupus donors in vivo or lupus DCs directly with UMI-77. UMI-77 also restored mitochondrial function in myeloid cells from patients with LN in vitro as evidenced by increased ATP levels. Thus, enhancing mitophagy in SLE restrains autoimmunity and limits kidney inflammation for LN development. Hence, our findings suggest targeting mitophagy as a tangible pathway to treat LN.

Predictors of renal relapse in Koreans with lupus nephritis after achieving complete response: a 35-years of experience at a single center.

Renal relapse has known to be a poor prognostic factor in patients with lupus nephritis (LN), but there were few studies that identified the risk factors of renal relapse in real world. We conducted this study based on 35-years of experience at a single center to find out predictors of renal relapse in Korean patients with LN after achieving complete response (CR). We retrospectively analyzed the clinical, laboratory, pathologic and therapeutic parameters in 296 patients of LN who reached CR. The cumulative risk and the independent risk factors for renal relapse were examined by Kaplan-Meier methods and Cox proportional hazards regression analyses, respectively. The median follow-up period from CR was 123 months. Renal relapse had occurred in 157 patients. Renal relapse occurred in 38.2%, 57.6% and 67.9% of patients within 5-, 10-, and 20-year, respectively. The age at diagnosis of SLE and LN were significantly younger, and the proportions of severe proteinuria and serum hypoalbuminemia were higher in patients with renal relapse. Interestingly, the proportion of receiving cytotoxic maintenance treatment was higher in patients with renal relapse. In Cox proportional hazards regression analyses, only young-age onset of LN (by 10 years, HR = 0.779, p = 0.007) was identified to independent predictor of renal relapse. Young-age onset of LN was only independent predictor and the patients with severe proteinuria and serum hypoalbuminemia also tended to relapse more, despite of sufficient maintenance treatment. Studies on more effective maintenance treatment regimens and duration are needed to reduce renal relapse.

GC/MS and LC/MS serum metabolomic analysis of Chinese LN patients

China, being a densely populated nation, faces a substantial economic burden due to a high incidence of lupus nephritis (LN) cases. The concealed onset of LN has resulted in many individuals have missed the optimal timing for treatment. The aim of the research is to study the serum metabolomics of Chinese LN patients using gas chromatography (GC)/mass spectrometry (MS) and liquid chromatography (LC)/MS to identify potential diagnostic markers. Fifty LN patients and fifty normal controls, matched for Body Mass Index (BMI) and age, were selected. Serum analysis was conducted using GC/MS and LC/MS, followed by multivariate statistical analysis. Various multidimensional analyses, including principal component analysis, partial least squares discrimination analysis, and orthogonal partial least squares discrimination analysis, along with one-dimensional analyses such as t-tests, were performed. Metabolites with variable importance in projection value > 1 and a p-value < 0.05 were considered critical biomarkers for LN. Furthermore, identified biomarkers delineated relevant metabolic pathways, and a metabolic pathway map was obtained from the database. Forty-one metabolites were identified as potential LN biomarkers, primarily associated with immune regulation, energy metabolism, intestinal microbial metabolism, renal damage, and oxidative stress. The potential for diagnosing LN and other diseases through metabolomics is demonstrated. Future research should explore larger sample sizes, metabolomic comparisons across different diseases and health states, and integration of metabolomics with clinical diagnostics. Such studies will enhance the understanding of metabolomics in medical diagnosis and provide robust support for its practical application.

Clinicopathologic characteristics and outcomes of late onset lupus nephritis: a single centre experience.

Systemic Lupus Erythematosus (SLE) occurs in the reproductive age group. Renal involvement occurs less frequently in late-onset SLE than in reproductive-age SLE patients. Here, we aimed to study the clinical, serological and histopathological characteristics of late-onset lupus nephritis (LN). Late-onset LN was defined as disease onset after 47years of age, corresponding to the average menopausal age. Records of biopsy proven late-onset lupus nephritis patients diagnosed between June 2000 and June 2020 were reviewed. Late-onset LN constituted 53 of 4420 patients (1.2%) biopsied during the study period. Females represented 90.65% of the cohort. Mean age of the cohort was 49.5 ± 7.05years at the time of SLE diagnosis while its renal presentation was delayed by median duration of 10months (IQR 3-48months). Renal failure was present in 28 patients (52.8%) with acute kidney injury (AKI) (28.3%, n = 15) as the most common presentation. On histopathological analysis, class IV was observed in 23 patients (43.5%), crescents were observed in one-third cases and lupus vasculopathy in 4 patients (7.5%). All patients received steroids. Majority of patients (43.3%; n = 23) received Euro lupus protocol for induction. On median follow up duration of 82months, renal flares were noted in 9 patients (17%) and 8 patients (15.1%) became dialysis dependent. Among 11 patients (21%) with infectious complications, 7 patients (13.2%) suffered from tuberculosis. Infections caused three-fourth of the deaths. Late-onset lupus nephritis is rare and presents as renal failure in majority. Renal biopsy affects the clinical decision of judicious use of immunosuppression which is imperative due to high rate of infections in this cohort.

#5081 THE VALUE OF ANTI-C1Q ANTIBODIES IN PREDICTING THE CLINICAL-HISTOLOGICAL FEATURES OF LUPUS NEPHRITIS PATIENTS AT TIME OF KIDNEY BIOPSY

Abstract Background and Aims Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with renal involvement in around 50% of patients. Delayed diagnosis of lupus nephritis (LN) is associated with higher risk of end-stage kidney disease (ESKD) and mortality. Kidney biopsy remains the gold standard for diagnosis and management of LN, but in the last decades there is an interest for new serum biomarkers. Anti-C1q antibodies are autoantibodies associated with LN. Nevertheless, few studies have correlated the association of anti-C1q antibodies with active LN with focus on renal histology. Method We evaluated clinical and histological data of 59 patients with biopsy proven LN. Kidney biopsies were categorized following the ISN/RNP Classification. We evaluated the correlation of the main clinicopathologic features with values of antiC1q antibodies, measured by a commercial kit with a clinically validated ELISA test. Normal values of antiC1q were &amp;lt; 20 UA, medium values were between 20 and 80 UA and high values were &amp;gt; 80 UA. Demographic and clinical data were expressed as numbers or percentage for discrete variables and for continuous variables as mean and standard deviation. The correlation between antiC1q levels and clinicopathological characteristics have been analyzed with Fisher's test. Results At the presentation of 59 patients with LN, the mean age was 34 years and the time of SLE disease before the onset of LN was 73.2 months. 9 patients were male, mean serum creatinine was 1 mg/dl, glomerular filtration rate (eGFR) was 88.53 ml/min, proteinuria was 4.35 g/day and microscopic hematuria was present in 79% of pts. Kidney biopsies were classified as non-proliferative (class II and V) in 18.4% of patients and proliferative (class III and IV) in 77.6% of patients. We evaluated the correlation between all variables included in Table 1 with values of antiC1q antibodies and we found significant results for serum creatinine, active urinary sediment, C3 and C4 values, proliferative classes and the activity index at kidney biopsy (Table 2). Conclusion High titles of anti-C1q antibodies were significantly correlated with the main clinical and histological characteristics that identify active renal diseases in SLE. Kidney biopsy remains the gold standard for diagnosis and management of LN, but anti-c1q antibodies are strongly associated with active LN in SLE. In conclusion, anti-C1q monitoring should be helpful and might be a crucial serum biomarker for the diagnosis and follow-up of these patients.

#4928 CLINICAL AND HISTOLOGICAL CHARACTERISTICS AND LONG-TERM PROGNOSIS OF LATE-ONSET LUPUS NEPHRITIS

Abstract Background and Aims Systemic lupus erythematosus (SLE) occurs mainly occurs in young women of child-bearing age and is not commonly found in the elderly population. Several studies suggest that the age at the onset of the disease has an influence on the course and the prognosis of the disease. Some studies have described that an early onset of lupus nephritis (LN) has a worse prognosis than a late-onset, presenting with greater complications and higher mortality, whereas other studies have shown that late-onset SLE present higher rate of organ damage and mortality. There are no series of late-onset LN that have been described in a European population to date. The KDIGO guidelines do not distinguish early from late-onset LN regarding their immunosuppression strategy recommendations The objective of this study was to compare the presentation, course and outcomes of late-onset LN compared to early-onset LN in a Spanish population, and detect differences in outcomes according to treatment received. Method We performed an observational retrospective multicenter study that included adult patients who developed LN confirmed by a kidney biopsy after the age of 50 years, defined as late-onset LN. We compared them to a group of selected patients aged younger than 50 years at the diagnosis (early-onset LN), matched for disease duration. Baseline demographic, clinical, serological and histological characteristics were compared between both groups. We compared the course of the disease in both groups including renal flares, serious adverse effects, and a composite outcome defined as doubling serum creatinine, developing end-stage kidney disease and/or death. Cox regression analysis was used to examine the association between late-onset LN and its outcomes. Results The study included 229 patients; 67 with late-onset LN and 162 early-onset LN patients. Late-onset LN patients presented more frequently hypertension (p&amp;lt;0.001) and diabetes (p = 0.008). There was a lower frequency of cutaneous manifestations (p &amp;lt;0.001) and oral ulcers (p = 0.008), higher frequency of hematological manifestations (p = 0.015) and Sjogren syndrome (p = 0.05). Patents with late-onset LN showed a worse baseline kidney function (p&amp;lt;0.001) and higher serum complement levels (p&amp;lt;0.001). Late-onset LN patients showed higher chronicity indices in kidney biopsies, with more glomerulosclerosis (p = 0.003), interstitial fibrosis (p = 0.021) and tubular atrophy (p = 0.011). There were no differences in the distribution of LN histological classification between both groups. We did not find significant differences between early and late-onset LN as regards induction and maintenance immunosuppression therapies, showing only a lower rate of antimalarial drug use in late-onset LN as maintenance therapy (p = 0.001). After a median follow-up of 7.4 (2.8-13) years, patients with late-onset LN showed a lower number of flares (p = 0.015), and a higher rate of serious adverse events related to immunosuppression, particularly infectious complications (34.3% vs 18.5%, p = 0.01). There were no differences in complete or partial remission or kidney function between both groups at the end of follow-up, however mortality was higher in late-onset LN patients, developing more frequently the composite outcome (19.4% vs 8%, p = 0.014). No significant difference was found in kidney survival (log-rank chi-square = 2.09, p = 0.148). Cox regression analysis showed that late-onset LN (hazard ratio = 3.26, 95% CI 1.18-8.98, p = 0.02), % sclerosed glomeruli (HR = 1.03, 95% CI 1.01-1.06, P = 0.019) and presence of severe side effects related to immunosuppression (HR = 10.09, 95% CI 3.2-31.7, p&amp;lt;0.001) were independent risk factors for reaching the composite outcome. Conclusion Although patients with late-onset LN present with worse kidney function and more severe chronic lesions in kidney biopsy, they show comparable kidney outcomes to patients with early-onset LN, and despite receiving similar immunosuppressive regimens they develop less renal flares but more serious adverse events, leading to a worse overall outcome. Minimization of immunosuppression regimens in late-onset LN may be an adequate option to improve patient outcomes.

Long-term impact of pregnancy on renal function among Egyptian women with lupus nephritis: A case control study.

Few studies tackled the long-term effect of pregnancy on lupus nephritis (LNs); thus, the study aimed to explore the long-term impact of pregnancy on renal outcomes in Egyptian patients with LN. Group I patients included females who had their first pregnancy after LN onset with ≥5years elapsing after delivery; group II patients included females who had never got pregnant for ≥7years after LN onset. Data were retrospectively collected at baseline (T0) and the last visit (Tlast). The study included 43 patients in group I and 39 patients in group II. The comparisons between the two groups regarding the characteristics at Tlast showed no significant difference regarding the serum creatinine, estimated glomerular filtration rate (eGFR), renal component of SLICC/ACR Damage Index (SDI) as well as the rate of renal flares, new-onset chronic kidney disease (CKD), progressed CKD and end-stage renal disease. Multivariate regression analysis revealed that systemic hypertension and renal flares were predictors of new-onset/progressed CKD (p = 0.019, OR [95% CI] = 4 [1.3-13]; and 0.022, 13.8 [1.5-128.8], respectively) while pregnancy was not (p = 0.363). Paired comparisons between T0 and Tlast characteristics within each group revealed significant increment of serum creatinine, renal SDI and CKD prevalence; as well as decrement of eGFR in group I (p = 0.004, <0.001, 0.001 and <0.001, respectively) and group II (p = 0.006, <0.001, 0.004 and 0.002, respectively). In conclusion, pregnancy, per se, does not affect the long-term renal outcome in LN patients; however, it is rather dependent on the existence of baseline renal damage and the development of renal flares.

Very Late Onset Lupus Nephritis: Single-Centre Experience and A Review of the Literature

Background: In the majority of lupus patients, lupus nephritis (LN) develops within the first five years of diagnosis. Here we evaluated patients treated in our department during the past 40 years distinguishing those with very early onset [within one year of diagnosis]; early onset [ two to five years post diagnosis]; medium-term onset [between six to ten years after diagnosis]; late onset [presenting six to 15 years after diagnosis] and very late onset LN [presenting 16 years or later after diagnosis]. Early onset [ two to five years post diagnosis]; medium-term onset [between six to ten years after diagnosis]; late onset [presenting six to 15 years after diagnosis] and very late onset LN [presenting 16 years or later after diagnosis].early onset [within two years of diagnosis]; medium-term onset [between two and five years after diagnosis]; late onset [presenting five to ten years after diagnosis] and very late onset LN [presenting ten years after diagnosis]. Aim: To compare the differences in demography, clinical data, serological profile and follow up of patients with LN of early, medium, late and very late onset. Methods: This was a retrospective study of 226 systemic lupus erythematosus (SLE) patients with biopsy proven nephritis. We focused on a comparison of their epidemiology, serology, clinical and follow-up data. Results: We identified 97 (43%) very early-onset patients; 69 (31%) early-onset; 28 (12%) medium onset; 22 (10%) late-onset and 10 (4%) very late-onset LN patients. Comparing those patients whose LN was delayed by&gt; 10 years post their lupus diagnosis compared to those with LN onset &lt;10 years we found that these patients were statistically significantly more likely to be Caucasian [p=0.04]; to have arthritis [p=0.001] and to be leucopaenic [p=0.004]. There were no other difference between the groups. Among the 10 patients with very late onset LN there was an increase trend towards them having higher ANA titer (&gt;1:640) [p=0,044] and having biopsy-proven combined type of LN (III+V, IV+V) [p=0.034]. Conclusion: Although the majority of SLE patients who get LN do so within 10 years of diagnosis in our experience 14% [approximately 1:7] developed renal involvement 10 years or more after SLE diagnosis. The observation emphasis the need to be vigilant when caring for SLE patients long term.

The long-term outcome of New Zealand Maori and Pacific Island children diagnosed with childhood onset lupus nephritis.

To determine the long-term outcome of Maori and Pacific Island children diagnosed with childhood onset lupus nephritis. A chart review was conducted of children diagnosed with biopsy proven lupus nephritis seen by the Starship Hospital and Kidz First paediatric rheumatology and/or Starship renal services between January 1992 and January 2018. Baseline and follow-up kidney histology, adherence and response to therapy including partial or full renal remission, refractory disease, end-stage kidney disease (ESKD) and mortality were determined. In a New Zealand cohort of 42 with childhood onset lupus nephritis, Maori and Pacific Island children were significantly more likely to develop class 4 lupus nephritis (RR (95% CI), 11.3 (3.84-49.9), p < 0.0001), demonstrate medication nonadherence (RR (95% CI) 12.4 (3.48-85.7), p < 0.0001) and experience end stage kidney disease (RR (95% CI) 15.7 (2.97-389.3), p = 0.0003) and mortality (RR (95% CI) 11.1 (1.91-280.1), p = 0.005) compared to non-Maori and Pacific Island children. In addition, Maori children with childhood onset lupus nephritis developed chronic histological changes significantly more rapidly than Pacific or Asian children (p = 0.038). Lupus nephritis is more common among Maori and Pacific Island children in New Zealand associated with a significant incidence of end stage kidney disease and mortality, with some Maori children developing rapid histologic disease progression.

Kidney biopsy in lupus nephritis after achieving clinical renal remission: paving the way for renal outcome assessment.

The role of repeat kidney biopsy in lupus nephritis (LN) with renal remission is unclear. The aim of this study was to assess this role in a real-life scenario. This retrospective, single-centre study included 56 patients with LN diagnosed from 1998 to 2019, with an initial kidney biopsy (KB1) at the onset of LN and a second kidney biopsy (KB2) after achieving renal remission. A total of 51 (91.1%) patients were women with a median age of 29.9 years [interquartile range (IQR) 23.4-40.6] at the time of LN diagnosis. KB2s were performed after 41.1 months (IQR 30.1-52.5) of KB1. At the time of KB2, complete renal response was achieved in 51 (91.1%) patients. The median activity index decreased from a baseline value of 6.5 (IQR 2.8-11) to 0 (IQR 0-2) (P<.001). The chronicity index worsened from 1 (IQR 0-2) to 2 (IQR 1-3) (P=.01). In patients with proliferative/mixed forms at KB2, the chronicity index median value increased to 3 (IQR 1.5-4), as well as interstitial fibrosis and tubular atrophy [Formula: see text]25%, from 5.4% to 13.5%. Persistent histological active LN (activity index≥2) was present in 11 (19.6%) KB2s. There were no differences when comparing immunological parameters between both groups (activity index≥2 versus<2)at KB2, nor in the percentage of patients who presented renal flare. Immunosuppressive treatment was withdrawn in 35 (62.5%) patients and maintained/switched in 21 (37.5%). Afterward, new renal flare occurred in 9 patients per group (25.7% and 43%, respectively), after a median time of 39 months (IQR 6.5-55) and 7 months (IQR 6-30), respectively. There was no difference in the number of patients who developed chronic kidney disease [n=14 (25%)] according to the treatment. In conclusion, KB2 provides valuable information to guide immunosuppressive maintenance therapy.

Restoration of Follicular T Regulatory/Helper Cell Balance by OX40L-JAG1 Cotreatment Suppresses Lupus Nephritis in NZBWF1/j Mice.

Class-switched antinuclear autoantibodies produced by T follicular helper (TFH) cell-dependent germinal center (GC) B cell response play an essential pathogenic role in lupus nephritis (LN). The role of T follicular regulatory (TFR) cells, an effector subset of CD4+Foxp3+ T regulatory cells (Tregs), which are specialized in suppressing TFH-GC response and Ab production, remains elusive in LN. Contrasting reports have shown increased/reduced circulating TFR cells in human lupus that might not accurately reflect their presence in the GCs of relevant lymphoid organs. In this study, we report a progressive reduction in TFR cells and decreased TFR/TFH ratio despite increased Tregs in the renal lymph nodes of NZBWF1/j mice, which correlated with increased GC-B cells and proteinuria onset. Cotreatment with soluble OX40L and Jagged-1 (JAG1) proteins increased Tregs, TFR cells, and TFR/TFH ratio, with a concomitant reduction in TFH cells, GC B cells, and anti-dsDNA IgG Ab levels, and suppressed LN onset. Mechanistic studies showed attenuated TFH functions and diminished GC events such as somatic hypermutation and isotype class-switching in OX40L-JAG1-treated mice. RNA sequencing studies revealed inhibition of hypoxia-inducible factor 1-α (HIF-1a) and STAT3 signaling in T conventional cells from OX40L-JAG1-treated mice, which are critical for the glycolytic flux and differentiation into TFH cell lineage. Therefore, the increased TFR/TFH ratio seen in OX40L-JAG1-treated mice could involve both impaired differentiation of TFH cells from T conventional cells and expansion of TFR cells. We show a key role for GC-TFR/TFH imbalance in LN pathogenesis and how restoring homeostatic balance can suppress LN.

CD11c+ T-bet+ CD21hi B Cells Are Negatively Associated With Renal Impairment in Systemic Lupus Erythematosus and Act as a Marker for Nephritis Remission.

Lupus nephritis (LN) is one of the most common manifestations of systemic lupus erythematosus (SLE), characterized by abnormal B cell activation and differentiation to memory or plasma effector cells. However, the role of these cells in the pathogenesis of LN is not fully understood, as well as the effect of induction therapy on B cell subsets, possibly associated with this manifestation, like aged-associated B cells (ABCs). Consequently, we analyzed the molecules defining the ABCs subpopulation (CD11c, T-bet, and CD21) through flow cytometry of blood samples from patients with lupus presenting or not LN, following up a small sub-cohort after six months of induction therapy. The frequency of ABCs resulted higher in LN patients compared to healthy subjects. Unexpectedly, we identified a robust reduction of a CD21hi subset that was almost specific to LN patients. Moreover, several clinical and laboratory lupus features showed strong and significant correlations with this undefined B cell subpopulation. Finally, it was observed that the induction therapy affected not only the frequencies of ABCs and CD21hi subsets but also the phenotype of the CD21hi subset that expressed a higher density of CXCR5. Collectively, our results suggest that ABCs, and more importantly the CD21hi subset, may work to assess therapeutic response since the reduced frequency of CD21hi cells could be associated with the onset of LN.

Chronic kidney disease in Korean patients with lupus nephritis: over a 35-year period at a single center.

Chronic kidney disease (CKD) is a major risk factor for overall morbidity and mortality even in lupus nephritis (LN) patients. However, less attention has been paid to the development of CKD in patients with LN. The objective of this study was to identify predictors for CKD with 35-year experience depending on newly revised guidelines for patients with LN. We conducted a retrospective cohort study for 401 patients who visited Seoul St. Mary's Hospital between January 1985 and December 2019. We analyzed clinical and laboratory indices, treatment response, the final renal function, and biopsy findings. The timing and cumulative risk of developing CKD were identified by Kaplan-Meier methods. Independent risk factors for developing CKD were examined by Cox proportional hazard regression analyses. The median follow-up time after the diagnosis of LN was 131months. CKD occurred in 15.5% of patients within 10years after the diagnosis of LN. The development of CKD was associated with delayed-onset LN, acute renal dysfunction at onset of LN, and failure to reach complete response (CR) at 6 or 12months rather than histopathological findings or the severity of proteinuria at onset of LN. Cumulative incidence of progression to CKD was significantly higher in patients with the three predictors mentioned above. Ten-year cumulative incidence of CKD was about 15%. Our results showed that delayed-onset LN, acute renal dysfunction at the onset of LN, and inadequate treatment response assessed at 6 or 12months after treatment were predictors for the development of CKD in LN. Key Points • CKD is a major risk factor for overall morbidity and mortality in LN patients. • Ten-year cumulative incidence of CKD was about 15% • Delayed-onset LN, acute renal dysfunction at the onset of LN, and inadequate treatment response assessed at 6 or 12months after treatment were predictors for the development of CKD in LN.