scholarly journals POS1452 DE NOVO LUPUS NEPHRITIS FOLLOWING THE INTRODUCTION OF BELIMUMAB

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1010.2-1010
Author(s):  
J. Pinnell ◽  
S. Tosounidou
Keyword(s):  
Lupus Nephritis ◽  
Renal Disease ◽  
Lupus Erythematosus ◽  
B Lymphocyte ◽  
De Novo ◽  
Controlled Trial ◽  
Significant Rise ◽  
Serological Response ◽  
Active Monitoring ◽  
Sledai Score

Background:Belimumab inhibits the activity of the soluble cytokine BLyS (B lymphocyte stimulator) and is recommended for use in moderate refractory systemic lupus erythematosus (SLE). A recent randomised controlled trial reported that Belimumab improves the outcomes for patients with lupus nephritis when used with standard therapy.Objectives:We present two cases of lupus nephritis that developed in SLE patients without pre-existing renal disease shortly after commencing treatment with Belimumab.Methods:Both patients are Afro-Caribbean females with similar immunological profiles, including ANA, dsDNA, anti-Sm, anti- Ro and anti-RNP antibodies. The first was 59 years old with a long standing diagnosis of SLE since 1996 that had required previous Cyclophosphamide for neuropsychiatric lupus. She was most recently taking Hydroxychloroquine, Mycophenolate and Prednisolone having previously failed with Azathioprine twice. Belimumab was commenced in February 2020 due to worsening arthritis, mouth ulcers, pleuritis and systemic features associated with a significant rise in her dsDNA and low complement. Her SLEDAI score was 13. After six months of treatment she developed proteinuria for the first time. Her urine protein creatinine ratio (uPCR) was measured at 205mg/mmol and a subsequent renal biopsy revealed features of active Class IV and V lupus nephritis. Belimumab was changed to Rituximab. Mycophenolate was stopped due to persistent neutropenia and Tacrolimus was introduced instead. After 5 months treatment her uPCR is now 33mg/mmol.The second patient was 37 years old with a recent diagnosis of SLE in 2018. She presented with inflammatory arthritis, oral and nasal ulcers, and cytopenia. She responded poorly to Azathioprine and was intolerant of Mycophenolate. Her most recent treatment was Hydroxychloroquine and Prednisolone. She was commenced on Belimumab in February 2020 due to active mucocutaneous and musculoskeletal features of lupus with a SLEDAI score of 12. The mucocutaneous features of lupus responded well but she developed proteinuria seven months later, and by November 2020 her uPCR was 149mg/mmol. Belimumab was switched to Rituximab and initially her uPCR continued to rise but it has now fallen to 43mg/mmol.Results:The occurrence of new lupus nephritis soon after the initiation of Belimumab monotherapy has been reported previously and our cases raise further concerns. A prospective observational study recently reported significantly increased rates of new lupus nephritis developing in patients receiving Belimumab in addition to standard care compared to those receiving standard treatment. An association between Belimumab and the development of de novo lupus nephritis has not yet been conclusively established but it would create a significant challenge in how Belimumab is used and consented for in SLE, especially if it becomes more widely used to treat lupus nephritis. The mechanism by which Belimumab may increase the risk of, or trigger, lupus nephritis is currently unclear but may result from increased activity in BLyS associated pathways following the blockade of the BLyS pathway.Conclusion:These two cases raise questions about the role of using Belimumab in patients at risk of developing lupus nephritis. We therefore recommend caution in its use and recommend active monitoring of renal parameters especially in patients with poor clinical and serological response to Belimumab.References:[1]Furie R, Rovin BH, Houssiau F, et al. Two-year, randomized, controlled trial of belimumab in lupus nephritis. N Engl J Med. 2020; 383(12):1117-28[2]Sjöwall C, Cöster L. Belimumab may not prevent lupus nephritis in serologically active patients with ongoing non-renal disease activity. Scand J Rheumatol. 2014; 43(5):428-30[3]Staveri C, Karokis D, Liossis SN. New onset of lupus nephritis in two patients with SLE shortly after initiation of treatment with belimumab. Semin Arthritis Rheum. 2017; 46(6):788-790[4]Parodis I, Vital EM, Hassan SU, et al. De novo lupus nephritis during treatment with belimumab. Rheumatology. 2020; keaa796Disclosure of Interests:None declared

scholarly journals Stronger Correlation between Interleukin 18 and Soluble Fas in Lupus Nephritis Compared with Mild Lupus

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Mohammad Reza Hatef ◽  
Maryam Sahebari ◽  
Zahra Rezaieyazdi ◽  
Mohammad Reza Nakhjavani ◽  
Mahmoud Mahmoudi
Keyword(s):  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Serum Markers ◽  
Significant Rise ◽  
Organ Involvement ◽  
Serum Concentrations ◽  
Interleukin 18 ◽  
Sledai Score ◽  
Soluble Fas ◽  
Major Organ

Lupus nephritis (LN) is a major cause of morbidity in patients with systemic lupus erythematosus (SLE). Several cytokines and apoptotic markers such as IL-18 and soluble Fas (sFas) have been assumed to play a role in the pathogenesis of LN. Previous studies confirmed that serum concentrations of sFas and IL-18 are increased in SLE. However, only a few studies have suggested a possible correlation between IL-18 and sFas. This study was planned to continue our previous study on the correlation between those markers to evaluate this correlation in LN. Thirty-two patients with only LN and 46 patients without any major organ involvement participated in this study. SLEDAI score (except for scores related to nephritis) was the same in these two groups. In both groups, patients with any other major organ involvement were excluded. We found a significant rise in the serum concentrations of sFas (P=0.03) and IL-18 (P=0.02) in patients with proteinuria compared to those without it. This study showed that the correlation between sFas and IL-18 in LN (P<0.001, rp=0.5) is significantly stronger than it is in mild SLE (P<0.001, rp=0.4) with similar nonrenal SLEDAI score (P=0.032, z=1.85). Between these two serum markers, sFas is the only predictor of proteinuria.

Expression of XBP1s in B lymphocytes is critical for pristane-induced lupus nephritis in mice

2020 ◽  
Vol 318 (5) ◽  
pp. F1258-F1270 ◽  
Author(s):  
Li Xiang ◽  
An Liu ◽  
Guoshuang Xu
Keyword(s):  
B Cells ◽  
Lupus Nephritis ◽  
Mouse Model ◽  
B Cell ◽  
Lupus Erythematosus ◽  
Cell Activation ◽  
B Lymphocyte ◽  
B Cell Activation ◽  
Protein Levels ◽  
Almost All

B lymphocyte hyperactivity plays a pathogenic role in systemic lupus erythematosus (SLE), and spliced X box-binding protein 1 (XBP1s) has been implicated in B cell maturation and differentiation. We hypothesized that blockade of the XBP1s pathway inhibits the B cell hyperactivity underlying SLE and lupus nephritis (LN) development. In the present study, we systematically evaluated the changes in B cell activation induced by the Xbp1 splicing inhibitor STF083010 in a pristane-induced lupus mouse model. The lupus mouse model was successfully established, as indicated by the presence of LN with markedly increased urine protein levels, renal deposition of Ig, and mesangial cell proliferation. In lupus mice, B cell hyperactivity was confirmed by increased CD40 and B cell-activating factor levels. B cell activation and plasma cell overproduction were determined by increases in CD40-positive and CD138-positive cells in the spleens of lupus mice by flow cytometry and further confirmed by CD45R and Ig light chain staining in the splenic tissues of lupus mice. mRNA and protein expression of XBP1s in B cells was assessed by real-time PCR, Western blot analysis, and immunofluorescence analysis and was increased in lupus mice. In addition, almost all changes were reversed by STF083010 treatment. However, the expression of XBP1s in the kidneys did not change when mice were exposed to pristane and STF083010. Taken together, these findings suggest that expression of XBP1s in B cells plays key roles in SLE and LN development. Blockade of the XBP1s pathway may be a potential strategy for SLE and LN treatment.

scholarly journals Urinary Neutrophil Gelatinase-Associated Lipocalin to Monitor Lupus Nephritis Disease Activity

2015 ◽  
Vol 10 ◽  
pp. BMI.S27625 ◽  
Author(s):  
Hani Susianti ◽  
Jullyanny W. Wijaya ◽  
Ati Rastini ◽  
Kusworini Handono ◽  
Atma Gunawan ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Transforming Growth Factor ◽  
Activity Index ◽  
Disease Activity Index ◽  
Transforming Growth Factor Β1 ◽  
Sledai Score ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Neutrophil Gelatinase

Background This study was conducted to determine whether there is an association between urinary neutrophil gelatinase-associated lipocalin (uNGAL) and urinary transforming growth factor-β1 (uTGF-β1) with lupus nephritis (LN) disease activity. Methods Urine samples from 18 LN patients were collected every month for six months then examined for uNGAL, uTGF-β1, and renal domain Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score. Results The uNGAL levels were significantly different between active and inactive LN (P < 0.05). uTGF-β1 levels were not different between active and inactive LN (P > 0.05). There was a significant correlation between uNGAL levels and renal domain SLEDAI score (r= 0.417, P < 0.05). There was no correlation between uTGF-β1 levels and renal domain SLEDAI score (r = 0.031, P > 0.05). Conclusion uNGAL is better than uTGF-β1 for differentiation of active and inactive LN. uNGAL can be considered as a biomarker to monitor LN disease activity.

Neutrophil extracellular traps are a source of extracellular HMGB1 in lupus nephritis: associations with clinical and histopathological features

Lupus ◽  
2019 ◽  
Vol 28 (13) ◽  
pp. 1549-1557 ◽  
Author(s):  
L P Whittall-García ◽  
J Torres-Ruiz ◽  
A Zentella-Dehesa ◽  
M Tapia-Rodríguez ◽  
J Alcocer-Varela ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Activity Index ◽  
High Mobility ◽  
Disease Activity Index ◽  
Neutrophil Extracellular Traps ◽  
Hmgb1 Protein ◽  
Sledai Score ◽  
Histopathological Features ◽  
Extracellular Traps

Objective This study aimed to analyze the expression of the high mobility group box-1 (HMGB1) protein in neutrophil extracellular traps (NETs) of patients with lupus nephritis (LN) and its association with clinical and histopathological features of the disease. Methods Twenty-three patients with biopsy-confirmed LN and 14 systemic lupus erythematosus (SLE) patients with active disease (SLE Disease Activity Index (SLEDAI) score ≥ 6) and no evidence of LN were included. Clinical and laboratory features were recorded. NETs and the expression of HMGB1 were assessed by confocal microscopy, and serum HMGB1 levels were measured by ELISA. Results In comparison to patients without kidney disease, patients with LN had a higher expression of HMGB1 in spontaneous (57 vs. 30.4; p = 0.027) and lipopolysaccharide (LPS)-induced (55.8 vs. 24.9; p = 0.005) NETs. We found a positive correlation between serum HMGB1 and the expression of HMGB1 in LPS-induced NETs ( r = 0.447, p = 0.017). The expression of HMGB1 in spontaneous NETs correlated with SLEDAI score ( r = 0.514, p = 0.001), anti-dsDNA antibodies ( r = 0.467, p = 0.004), the rate of glomerular filtration descent ( r = 0.543, p = 0.001), and diverse histopathological components of active nephritis in the kidney biopsy, such as the activity index ( r = 0.581, p = 0.004), fibrinoid necrosis ( r = 0.603, p = 0.002), and cellular crescents ( r = 0.486, p = 0.019). Conclusions In patients with SLE, NETs are a source of extracellular HMGB1. The expression of HMGB1 in NETs is higher among patients with LN, which correlates with clinical and histopathological features of active nephritis and suggest a possible role of this alarmin in the pathophysiology of kidney damage in SLE.

scholarly journals Mizoribine: A New Approach in the Treatment of Renal Disease

2009 ◽  
Vol 2009 ◽  
pp. 1-10 ◽  
Author(s):  
Yukihiko Kawasaki
Keyword(s):  
Cell Cycle ◽  
Lupus Nephritis ◽  
Renal Disease ◽  
Iga Nephropathy ◽  
Lupus Erythematosus ◽  
Pulse Therapy ◽  
Immunosuppressive Agent ◽  
Immunosuppressive Drug ◽  
Steroid Dependent ◽  
Severe Lupus Nephritis

Mizoribine (MZB) is an imidazole nucleoside and an immunosuppressive agent. The immunosuppressive effect of MZB has been reported to be due to the inhibition of DNA synthesis in the S phase of the cell cycle. Because of its relative lack of toxicity, during the past decade MZB has been frequently used instead of azathioprine as a component of immunosuppressive drug regimens. MZB is being used to treat renal transplantation patients, IgA nephropathy, lupus erythematosus, and childhood nephrotic syndrome (NS), and some recent studies have assessed the efficacy of oral MZB pulse therapy for severe lupus nephritis, steroid-resistant NS, and frequently relapsing-steroid-dependent NS. This review summarizes the published findings on the efficacy of MZB for renal disease including IgA nephropathy, lupus nephritis, and NS, as well as of oral MZB pulse therapy for severe lupus nephritis and NS, and also the mechanism of the effect of oral MZB pulse therapy on the lymphocyte cell cycle.

Serum BLC/CXCL13 Concentrations and Renal Expression of CXCL13/CXCR5 in Patients with Systemic Lupus Erythematosus and Lupus Nephritis

2009 ◽  
Vol 37 (1) ◽  
pp. 45-52 ◽  
Author(s):  
HUI-TING LEE ◽  
YU-MING SHIAO ◽  
TSAI-HUNG WU ◽  
WEI-SHENG CHEN ◽  
YUNG-HSIANG HSU ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Flow Cytometry ◽  
B Cells ◽  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
B Lymphocyte ◽  
Venous Blood ◽  
Systemic Autoimmune Disease ◽  
Systemic Lupus ◽  
Serum Samples

Objective.Systemic lupus erythematosus (SLE) is a prototype of systemic autoimmune disease in which cytokines such as B lymphocyte chemoattractant (BLC, or CXC motif ligand 13, CXCL13) may play important roles in pathogenesis. We investigated the implications of CXCL13 in SLE and lupus nephritis.Methods.Serum samples from 425 patients with SLE and 106 healthy control individuals were analyzed for the concentration of CXCL13 by ELISA. Tissue expression of CXCL13 and its corresponding receptor CXCR5 were observed in lupus kidney. The CXCR5-bearing B cells in SLE patients were analyzed by flow cytometry.Results.Serum levels of CXCL13 were higher in SLE patients compared to controls. SLE patients with lupus nephritis or positive anti-dsDNA antibodies had significantly higher serum CXCL13 levels. The peripheral venous blood B cells that bear CXCR5 were more abundant in SLE patients as detected by flow cytometry. CXCR5 and CXCL13 were highly expressed in the renal cortex from patients with lupus nephritis.Conclusions.Our results suggest that BLC/CXCL13 as well as its corresponding receptor, CXCR5, may play important roles in the pathogenesis of SLE and in lupus nephritis.

scholarly journals Glucocorticoid Withdrawal in Lupus Nephritis: A Study Protocol and Literature Review

2020 ◽  
Vol 20 (02) ◽  
pp. 47-55
Author(s):  
Natalia Chu Oi Ciang ◽  
Chi Chiu Mok
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Randomized Controlled Trial ◽  
Lupus Nephritis ◽  
Literature Review ◽  
Lupus Erythematosus ◽  
Low Dose ◽  
Controlled Trial ◽  
Systemic Lupus ◽  
Randomized Controlled ◽  
Multicenter Rct

Although glucocorticoids (GCs) are the cornerstone for the treatment for systemic lupus erythematosus (SLE), they are associated with a number of adverse effects. Recently, an open randomized controlled trial (RCT) conducted in France showed that flares of SLE in 12 months were significantly more common with GCs withdrawal than continuation in stable patients. However, the study did not separately report results on subsets of SLE patients with organ threatening disease such as lupus nephritis (LN). We hereby present a literature review on GCs withdrawal in SLE and propose a protocol for a multicenter RCT in Hong Kong to evaluate the feasibility of withdrawal of low-dose GCs in stable LN patients who are in clinical remission.

Urinary Neutrophil Gelatinase-Associated Lipocalin as a Novel Predictor in Treatment of Active Lupus Nephritis

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Gamal E Mady ◽  
Sahar M Shawky ◽  
Walid A Bichari ◽  
Mohamed S Hassan ◽  
Ahmed M Tawfik ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Renal Disease ◽  
Induction Therapy ◽  
Lupus Erythematosus ◽  
Complete Response ◽  
Response To Treatment ◽  
Class Iii ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Response Groups ◽  
Neutrophil Gelatinase

Abstract Introduction Lupus nephritis (LN) affects almost two-thirds of Systemic lupus erythematosus (SLE) patients. Despite initial aggressive therapy, up to 25% of patients with LN will progress to end stage renal disease (ESRD). Conventional serum markers for LN lack the sensitivity of an ideal biomarker. Urinary Neutrophil gelatinase-associated lipocalin (UNGAL) is an excellent biomarker for early diagnosis of acute kidney injury and predicting renal outcomes. Objectives To measure UNGAL among LN patients correlating its levels with renal disease activity to investigate its predictive performance in response to induction therapy. Patients and Methods 40 SLE patients with biopsy-proven LN, class III, IV, or V were randomly selected. The study was conducted in internal medicine department and Outpatient clinic in Ain Shams University Hospitals on and completed after six months. UNGAL was measured at baseline and after complete induction therapy. Results In LN patients at baseline; mean UNGAL levels of complete response, partial response, and no response groups were 14.48 ±2.99 ng/ml, 34.49 ±4.09, and 62.07 ±14.44 ng/ml respectively. Based on ROC curve, we found better performance of baseline UNGAL to discriminate complete response group from partial and non-response groups to predict response to induction, outperforming conventional biomarkers. The area under the curve was 0.943 (92.31% sensitivity, 88.89% specificity), and the best cut-off level was 26.5 ng/ml. Conclusion UNGAL performed better than conventional biomarkers in predicting response to treatment of active LN.

scholarly journals Systemic lupus erythematosus, lupus nephritis and end-stage renal disease: a pragmatic review mapping disease severity and progression

Lupus ◽  
2020 ◽  
Vol 29 (9) ◽  
pp. 1011-1020
Author(s):  
Anadi Mahajan ◽  
Justyna Amelio ◽  
Kerry Gairy ◽  
Gavneet Kaur ◽  
Roger A Levy ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Nephritis ◽  
Renal Disease ◽  
Lupus Erythematosus ◽  
End Stage Renal Disease ◽  
Elevated Serum ◽  
Systemic Lupus ◽  
Histological Transformation ◽  
Stage Renal Disease ◽  
End Stage

Objective The understanding of systemic lupus erythematosus (SLE) and lupus nephritis (LN) pathogenesis remains incomplete. This review assessed LN development in SLE, within-LN progression and progression to end-stage renal disease (ESRD). Methods A keyword-based literature search was conducted, and 26 publications were included. Results Overall, 7–31% of patients had LN at SLE diagnosis; 31–48% developed LN after SLE diagnosis, most within 5 years. Class IV was the most commonly found LN class and had the worst prognosis. Histological transformation occurred in 40–76% of patients, more frequently from non-proliferative rather than proliferative lesions. Cumulative 5- and 10-year ESRD incidences in patients with SLE were 3% and 4%, respectively, and 3–11% and 6–19%, respectively, in patients with SLE and LN. Conclusions Elevated serum creatinine was identified as a predictor of worsening disease state, and progression within LN classes and from SLE/LN to ESRD. This review highlights the substantial risk for developing LN and progressing to ESRD amongst patients with SLE.

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