Lupus Nephritis

2019 ◽  
pp. 309-318
Author(s):  
Aisha Shaikh ◽  
Kirk N. Campbell
Keyword(s):  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Treatment Options ◽  
Disease Entity ◽  
Disease Remission ◽  
Renal Histology ◽  
Single Disease Entity ◽  
Histological Remission ◽  
Common Manifestation ◽  
Histological Form

Lupus nephritis (LN) is common manifestation of systemic lupus erythematosus and is associated with significant morbidity and mortality. LN is a not a single-disease entity; on the contrary, it encompasses a wide array of renal histological patterns. The treatment options and outcomes vary with the type of renal histology. Proliferative LN remains the most aggressive histological form of LN and requires aggressive treatment. The goal of therapy for LN is to achieve clinical and histological remission and avoid progression to chronic kidney disease. Remission of LN not only improves renal outcomes but also results in significant improvement in overall patient mortality. Though much progress has been made in this arena, there is still a need for therapeutic agents that are less toxic and more effective than the currently available therapies.

Association of coexisting anti-ribosomal P and anti-dsDNA antibodies with histology and renal prognosis in lupus nephritis patients

Lupus ◽  
2021 ◽  
pp. 096120332098390
Author(s):  
Ayako Wakamatsu ◽  
Hiroe Sato ◽  
Yoshikatsu Kaneko ◽  
Takamasa Cho ◽  
Yumi Ito ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Renal Outcome ◽  
Class V ◽  
Double Stranded Dna ◽  
Number Of Patients ◽  
Renal Histology ◽  
Renal Prognosis ◽  
Incidence Of Ckd ◽  
Ribosomal P

Objectives Anti-ribosomal P protein autoantibodies (anti-P) specifically develop in patients with systemic lupus erythematosus. Associations of anti-P with lupus nephritis (LN) histological subclass and renal outcome remain inconclusive. We sought to determine the association of anti-P and anti-double-stranded DNA antibody (anti-dsDNA) with renal histology and prognosis in LN patients. Methods Thirty-four patients with LN, having undergone kidney biopsy, were included. The 2018 revised ISN/RPS classification system was used for pathophysiological evaluation. Chronic kidney disease (CKD) was defined as an estimated glomerular filtration rate < 60 mL/min/1.73 m2 for > 3 months. Results Six patients (17.6%) were positive for anti-P and 26 (76.5%) for anti-dsDNA. Among the six patients with anti-P, one did not have anti-dsDNA, but did have anti-Sm antibody, and showed a histological subtype of class V. This patient maintained good renal function for over 14 years. The remaining five patients, who had both anti-P and anti-dsDNA, exhibited proliferative nephritis and were associated with prolonged hypocomplementemia, and the incidence of CKD did not differ from patients without anti-P. Conclusion Although this study included a small number of patients, the results indicated that histology class and renal prognosis associated with anti-P depend on the coexistence of anti-dsDNA. Further studies with a large number of patients are required to confirm this conclusion.

scholarly journals AB0124 NO EFFECTS OF HIGH DOSE 25OH-VITAMIN D SUPPLEMENTATION ON LUPUS NEPHRITIS IN AN ANIMAL MODEL OF SYSTEMIC LUPUS ERYTHEMATOSUS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1362.2-1362
Author(s):  
S. Barsotti ◽  
C. Tani ◽  
A. Kuhl ◽  
S. Pacini ◽  
S. Vagnani ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Vitamin D ◽  
Animal Model ◽  
Lupus Nephritis ◽  
Interstitial Nephritis ◽  
Lupus Erythematosus ◽  
Statistical Significance ◽  
High Dose ◽  
Systemic Lupus ◽  
Renal Histology

Background:25OH Vitamin D (25-OH-D3) is a fat-soluble steroid-derived molecule involved in the calcium homeostasis. Low levels of 25-OH-D3 are commonly found in patients with systemic lupus erythematosus (SLE) and have been correlated to higher disease activity and severity. Several recent studies have demonstrated that high dose Vitamin D may influence several aspects of the innate and adaptive immune response and some authors hypothesized that high dose 25-OH-D3 may have a role in the treatment of SLE. Despite these observations, the immunomodulatory effect of high dose 25-OH-D3in vivostill needs to be demonstrated.Objectives:The aim of our study was to identify the effect of 25-OH-D3 on proteinuria, survival and renal biopsy in New Zealand Black/White F1 mice (NZ), that develop a disease very similar to human SLE nephritis.Methods:We administered to 20 NZ mice a diet enriched with high dose 25-OH-D3 10,000 UI/Kg starting from 8 weeks of age. Mice were divided in 7 experimental groups (5 mice each). The first group was sacrificed before the start of the treatment (8 week of age), three groups were treated (treated mice – TM) with 25-OH-D3 and sacrificed at 16, 26 and 36 weeks of age. The other three groups were enrolled as controls and sacrificed at 16, 26 and 36 weeks of age respectively (untreated mice – UM). The parameters collected included: total urinary protein and kidney histology for the evaluation of lupus nephritis (LN): glomerulonephritis, interstitial nephritis and vascular lesions according to a 5 points scale to obtain a total score (ranging from 0 to 12).Results:In UM, proteinuria tended to increase over 1 mg/day at 12 weeks of age (1.7±0.43mg/day) and further increased until to reach a plateau after 28 weeks of age (10±2.0 mg/day).In TM, a significant increase in proteinuria over 1 mg/day was observed at 24 weeks, when the mean proteinuria was 1.7±1.33 which was lower than controls at the same age although without statistical significance (2.9±2.6); thereafter proteinuria started to increase also in treated mice and at week 30 was higher in TM compared with UM (10,3±8.8 vs 4.3±3.5 p=0.05). Figure 1.Kidney histology showed, in mice sacrificed before the start of the treatment no signs of LN. In mice sacrificed at 16 weeks minimal interstitial nephritis (score 1) was identified in 2 mice only in UM. At 26 weeks of age, a higher total LN score was identified in TM compared with UM (3.4±3.8 vs 0.4 ±0.9) with higher score for all three parameters analyzed. At 36 weeks of age, the TM group maintained a higher total LN score compared to UM (6.5±1.7 vs 6.0±2.6) with higher score for glomerulonephritis and interstitial nephritis.In the TM group, three mice spontaneously died at 26, 30 and 32 weeks of age, while in the UM only one mouse died at 36 weeks of age.Conclusion:Our data suggest that, in this animal model of SLE, 25-OH-D3 administration seems to delay the onset of proteinuria, although has no effect on the overall disease control. In addition, it may have a negative effect on renal histology and survival with earlier development of LN.Figure:Disclosure of Interests:None declared

scholarly journals An Update for Mesenchymal Stem Cell Therapy in Lupus Nephritis

2021 ◽  
Vol 7 (2) ◽  
pp. 79-89
Author(s):  
Wenchao Li ◽  
Weiwei Chen ◽  
Lingyun Sun
Keyword(s):  
Stem Cell ◽  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Mesangial Cells ◽  
Treatment Options ◽  
Novel Therapy ◽  
Mesenchymal Stem Cell Therapy ◽  
Allogeneic Mscs ◽  
Senescent Phenotype ◽  
Organ Manifestations

Background: Lupus nephritis (LN) is the most severe organ manifestations of systemic lupus erythematosus (SLE). Although increased knowledge of the disease pathogenesis has improved treatment options, outcomes have plateaued as current immunosuppressive therapies have failed to prevent disease relapse in more than half of treated patients. Thus, there is still an urgent need for novel therapy. Mesenchymal stem cells (MSCs) possess a potently immunosuppressive regulation on immune responses, and intravenous transplantation of MSCs ameliorates disease symptoms and has emerged as a potential beneficial therapy for LN. The objective of this review is to discuss the defective functions of MSCs in LN patients and the application of MSCs in the treatment of both LN animal models and patients. Summary: Bone marrow MSCs from SLE patients exhibit impaired capabilities of migration, differentiation, and immune regulation and display senescent phenotype. Allogeneic MSCs suppress autoimmunity and restore renal function in mouse models and patients with LN by inducing regulatory immune cells and suppressing Th1, Th17, T follicular helper cell, and B-cell responses. In addition, MSCs can home to the kidney and integrate into tubular cells and differentiate into mesangial cells. Key Messages: The efficacy of MSCs in the LN treatment remains to be confirmed, and future advances from stem cell science can be expected to pinpoint significant MSC subpopulations, as well as specific mechanisms of action, leading the way to the use of more potent stimulated or primed pretreated MSCs to treat LN.

P0346THE EFFECTS OF RITUXIMAB MAINTENANCE THERAPY ON LUPUS NEPHRITIS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Matthias Cassia ◽  
Rachel B Jones ◽  
Daniele Cagna ◽  
Rona Smith ◽  
Giovanni Casazza ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Maintenance Therapy ◽  
Lupus Erythematosus ◽  
Treatment Options ◽  
Complete Response ◽  
Immunosuppressive Drugs ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Urinary Sediment ◽  
Renal Flare

Abstract Background and Aims Lupus Nephritis (LN) is the organ manifestation with the most severe prognosis in Systemic Lupus Erythematosus (SLE). Treatment options are limited due to partial efficacy, intolerance or side effects; moreover 10% of patients reach ESRD despite treatments. Rituximab (RTX) in LN is recommended as second line drug for induction of the remission after failure of Cyclophosphimide or Mycophenolate Mofetil. We have shown a role for RTX as maintenance therapy (RMT) in SLE however the effects of such approach on LN are still unclear. Aim of this study was a sub-analyses of a cohort of SLE patients treated with RTX focusing on the ones with active LN at the moment of the first RTX administration. Methods Patients with active LN at the time of the first RTX administration within a cohort of 147 patients with SLE were identified. Patients with SLE and a flare of LN were classified as treated with a “Single RTX course” (any RTX regimen administered within a single month) (SRC) or with RMT. Patients receiving at least three SRCs with the aim of relapse prevention and within 4 to 8 months between consecutive treatments, were classified as receiving RMT. LN activity was determined according to creatinine, proteinuria and haematuria; complete response (CR) was defined as a decrease of proteinuria to &lt;0.5 g/day, normal creatinine and negative urinary sediment; partial response (PR) was defined as ≥50% improvement in creatinine and proteinuria, treatment failure (TF) was any other condition. A renal flare (RF) was defined as an increase of creatinine and/or proteinuria &gt;30% or the detection of an active urinary sediment due, according to the treating physician, to active disease. Results 33 patients were identified; a renal biopsy had been performed in 76% with prevalence of class IV lupus nephritis in 16/33 (48%). Six months after RTX the rate of CR, PR and TF was respectively 36%, 27% and 36%; proteinuria and the prednisolone dose reduced significantly compared to baseline (respectively from a median of 2200 mg/day (IQR 499-5400) to 850 mg/day (IQR 400-1700) (p=0.005)) and from 25 mg (IQR 11-25) to 10 mg (IQR 6.125-15) (p&lt;0.0001)). At univariate analyses the only factor associate to the risk of TF was a high number of immunosuppressive drugs employed before RTX (p=0.0077). Of the 33 patients, 11 received RMT with a median duration of 18 months (IQR 12,6-23,4) and a median RTX dose of 5 g (IQR 4-6). During the RMT 3 patients experienced a renal flare. The median follow-up after the last RTX administration within the SRC and the RMT groups was respectively 15 months (IQR 13,5-18,4) and 16 months (IQR 3,5-23). Comparing the RF free-survival of the two subgroups after the last RTX infusion, there was a trend towards a longer relapse free survival after the RMT (p=0.057) (figure, left panel). Of interest, the renal relapse free-survival of the 11 patients treated with RMT after the last RTX infusion was significantly longer compared to the one of the same group after the first RTX (p=0.0271) (figure, right panel). The incidence of SAEs per 100 patient years was 0.31 in the SRC group and 0.74 in the RMT group. Conclusion RTX is confirmed as an effective option for patients with LN. A RMT may have a role in improving LN disease control compared to a single RTX administration.

scholarly journals Differences in Rituximab Use Between Pediatric Rheumatologists and Nephrologists for the Treatment of Refractory Lupus Nephritis and Renal Flare in Childhood-Onset Sle

2021 ◽  
Author(s):  
Mileka Gilbert ◽  
Beatrice Goilav ◽  
Joyce J. Hsu ◽  
Paul J. Nietert ◽  
Esra Meidan ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Treatment Options ◽  
Pediatric Nephrology ◽  
Response To Treatment ◽  
Induction Treatment ◽  
Childhood Onset ◽  
Renal Flare ◽  
Treatment Plans

Abstract Background: Consensus treatment plans have been developed for induction therapy of newly diagnosed proliferative lupus nephritis (LN) in childhood-onset systemic lupus erythematosus. However, patients who do not respond to initial therapy, or who develop renal flare after remission, warrant escalation of treatment. Our objective was to assess current practices of pediatric nephrologists and rheumatologists in North America in treatment of refractory proliferative LN and flare.Methods: Members of Childhood Arthritis and Rheumatology Research Alliance and the American Society for Pediatric Nephrology were surveyed in November 2015 to assess therapy choices (other than modifying steroid dosing) and level of agreement between rheumatologists and nephrologists for proliferative LN patients. Two cases were presented: 1) refractory disease after induction treatment with corticosteroid and cyclophosphamide and 2) nephritis flare after initial response to treatment. Survey respondents chose treatments for three follow up scenarios for each case that varied by severity of presentation. Treatment options included cyclophosphamide, mycophenolate mofetil, rituximab, and others, alone or in combination.Results: Treatment choices between nephrologists and rheumatologists were highly variable. A majority (>50%) consensus of either nephrologists or rheumatologists on treatment choice was only achieved in two of six total follow up scenarios for refractory LN or flare. Rheumatologists in comparison to nephrologists chose more therapy options that contained rituximab in five of six scenarios. These differences were statistically significant (p < 0.05). Conclusions: Therapy choices for pediatric rheumatologists and nephrologists in the treatment of refractory LN or LN flare were highly variable with rheumatologists more often choosing rituximab. Further investigation is necessary to delineate the reasons behind this finding. This study highlights the importance of collaborative efforts in developing consensus treatment plans for pediatric LN.

Combination immunosuppressant therapy and lupus nephritis outcome: a hospital-based study

Lupus ◽  
2019 ◽  
Vol 28 (5) ◽  
pp. 658-666
Author(s):  
Y M Chen ◽  
W T Hung ◽  
Y W Liao ◽  
C Y Hsu ◽  
T Y Hsieh ◽  
...  
Keyword(s):  
Risk Factors ◽  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Large Scale ◽  
Activity Index ◽  
Disease Activity Index ◽  
Induction Treatment ◽  
Tertiary Referral Center ◽  
Renal Histology ◽  
Chronicity Index

Lupus nephritis (LN) is the leading cause of mortality in lupus patients. This study aimed to investigate the treatment outcome and renal histological risk factors of LN in a tertiary referral center. Between 2006 and 2017, a retrospective observational study enrolled 148 biopsy-proven LN patients. After propensity score matching, 75 cases were included for further analysis. The classification and scoring of LN were assessed according to the International Society of Nephrology/Renal Pathology Society. Treatment response was evaluated by daily urine protein and urinalysis at two years after commencing induction treatment and the development of end-stage renal disease (ESRD). In total, 50.7% patients achieved complete remission (CR) or partial remission (PR), while 49.3% patients were categorized as nonresponders. Therapeutic responses in terms of CR/PR rates were associated with Systemic Lupus Erythematosus Disease Activity Index scores (odds ratio (OR): 1.34, 95% confidence interval (CI): 1.12–1.60, p = 0.001). Moreover, higher baseline creatinine levels (hazard ratio (HR): 2.10, 95% CI: 1.29–3.40, p = 0.003), higher renal activity index (HR: 1.30, 95% CI: 1.07–1.58, p = 0.008) and chronicity index (HR: 1.40, 95% CI: 1.06–1.85, p = 0.017) predicted ESRD. Among pathological scores, cellular crescents (HR: 4.42, 95% CI: 1.01–19.38, p = 0.049) and fibrous crescents (HR: 5.93, 95% CI: 1.41–24.92, p = 0.015) were independent risk factors for ESRD. In conclusion, higher lupus activity was a good prognostic marker for renal remission. Renal histology was predictive of ESRD. Large-scale prospective studies are required to verify the efficacy of mycophenolate in combination with azathioprine or cyclosporine in LN patients.

scholarly journals Targeting the B-Cell Pathway in Lupus Nephritis: Current Evidence and Future Perspectives

2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Panagiotis Pateinakis ◽  
Athina Pyrpasopoulou
Keyword(s):  
Clinical Trials ◽  
Lupus Nephritis ◽  
B Cell ◽  
Lupus Erythematosus ◽  
Cell Function ◽  
Current Knowledge ◽  
Treatment Options ◽  
Immunosuppressive Treatment ◽  
Current Evidence ◽  
Trial Duration

Nephritis represents a frequent, severe complication of systemic lupus erythematosus. Autoantibodies appear to be fundamental in the pathogenesis of lupus nephritis. Several hypotheses are currently experimentally tested to further elucidate the direct induction of inflammation through interaction of the pathological autoantibodies with intrinsic glomerular components and the triggering of a complement-driven autoinflammatory cascade. B-cells have, in the last decade, emerged as a promising new therapeutic target, as biological treatments successfully attempting B-cell depletion, inhibition of B-cell proliferation and differentiation, or modulation of B-cell function have become bioengineered. Clinical trials have so far proved controversial regarding the efficacy of these new agents. Thus, despite the short and long-term side effects associated with immunosuppressive treatment alternative emerging treatments are still regarded “rescue” regimens in refractory patients. In an effort to accurately evaluate the potential of these therapies in lupus nephritis, several issues have been raised mainly in terms of patient selection criteria and trial duration. This review aims to expand on the proposed pathophysiologic mechanisms implicating the B-cell pathway in the pathogenesis of lupus nephritis and summarize current knowledge obtained from clinical trials introducing these biologics in its treatment. Finally, it will elaborate on potential applications of currently available biologic agents and forthcoming treatment options.

Extraglomerular immune complex deposition in lupus nephritis

Lupus ◽  
2021 ◽  
pp. 096120332110625
Author(s):  
Valentina Papa ◽  
James Brainer ◽  
Kammi J Henriksen ◽  
Giovanna Cenacchi ◽  
Anthony Chang
Keyword(s):  
Electron Microscopy ◽  
Systemic Lupus Erythematosus ◽  
Retrospective Study ◽  
Lupus Nephritis ◽  
Immune Complex ◽  
Lupus Erythematosus ◽  
Systemic Lupus ◽  
Immune Complex Deposition ◽  
Complex Deposition ◽  
Common Manifestation

Background Lupus nephritis (LN) is a common manifestation and a major cause of morbidity and mortality in systemic lupus erythematosus (SLE) patients. It is characterized by glomerular and often extraglomerular immune complex deposition. Purpose Given the emerging importance of the tubulointerstitial compartment, we conducted a retrospective study of 78 LN biopsies to enumerate the spectrum of extraglomerular immune complex deposition that can be observed in lupus nephritis by electron microscopy and to identify possible clinical or pathologic correlates. Results The presence of tubulointerstitial immune complex deposition often accompanied interstitial inflammation, but some discrepancies were also seen. Conclusions As target antigens are identified, correlation with glomerular, tubulointerstitial, and vascular immune complex deposition will be of increasing interest.

scholarly journals Pediatric lupus nephritis

2019 ◽  
Vol 41 (2) ◽  
pp. 252-265 ◽  
Author(s):  
Sergio Veloso Brant Pinheiro ◽  
Raphael Figuiredo Dias ◽  
Rafaela Cabral Gonçalves Fabiano ◽  
Stanley de Almeida Araujo ◽  
Ana Cristina Simões e Silva
Keyword(s):  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Pediatric Patients ◽  
Treatment Options ◽  
Clinical Manifestations ◽  
Mortality Rates ◽  
Renal Tissue ◽  
Pediatric Lupus ◽  
General Aspects ◽  
Tissue Alterations

Abstract Involvement of the kidneys by lupus nephritis (LN) is one of the most severe clinical manifestations seen in individuals with systemic lupus erythematosus (SLE). LN is more frequent and severe in pediatric patients and has been associated with higher morbidity and mortality rates. This narrative review aimed to describe the general aspects of LN and its particularities when affecting children and adolescents, while focusing on the disease's etiopathogenesis, clinical manifestations, renal tissue alterations, and treatment options.

scholarly journals Delayed lupus nephritis in the course of systemic lupus erythematosus is associated with a poorer treatment response: a multicentre, retrospective cohort study in Japan

Lupus ◽  
2019 ◽  
Vol 28 (9) ◽  
pp. 1062-1073 ◽  
Author(s):  
M Nakano ◽  
K Kubo ◽  
Y Shirota ◽  
Y Iwasaki ◽  
Y Takahashi ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Cohort Study ◽  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Retrospective Cohort Study ◽  
Retrospective Cohort ◽  
Cox Regression ◽  
Complete Response ◽  
Systemic Lupus ◽  
Renal Histology

Objective The objective of this study was to investigate possible differences in treatment responses between two categories for the onset of lupus nephritis. Methods We performed a multicentre, retrospective cohort study of class III–V lupus nephritis patients diagnosed between 1997 and 2014. The renal responses to initial induction therapy were compared between patients who developed lupus nephritis within one year from diagnosis of systemic lupus erythematosus (early (E-) LN) and the remainder (delayed (D-) LN) using the Kaplan–Meier method. We determined the predictors of renal response as well as renal flares and long-term renal outcomes using multivariate Cox regression analyses. Results A total of 107 E-LN and 70 D-LN patients were followed up for a median of 10.2 years. Log-rank tests showed a lower cumulative incidence of complete response in D-LN compared with E-LN patients. Multivariate analysis identified D-LN (hazard ratio (HR) 0.48, 95% confidence interval (CI) 0.33–0.70), nephrotic syndrome at baseline, and a chronicity index greater than 2 as negative predictors of complete response. D-LN patients were more likely to experience renal flares. D-LN (HR 2.54, 95% CI 1.10–5.83) and decreased renal function were significant predictors of chronic kidney disease at baseline. Conclusion D-LN was a predictor of poorer treatment outcomes, in addition to renal histology and severity of nephritis at lupus nephritis onset.

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