scholarly journals Outcomes following mycophenolate mofetil versus cyclophosphamide induction treatment for proliferative juvenile-onset lupus nephritis

Lupus ◽  
2019 ◽  
Vol 28 (5) ◽  
pp. 613-620 ◽  
Author(s):  
EMD Smith ◽  
E Al-Abadi ◽  
K Armon ◽  
K Bailey ◽  
C Ciurtin ◽  
...  

Background Juvenile-onset systemic lupus erythematosus (JSLE) is more severe than adult-onset disease, including more lupus nephritis (LN). Despite differences in phenotype/pathogenesis, treatment is based upon adult trials. This study aimed to compare treatment response, damage accrual, time to inactive LN and subsequent flare, in JSLE LN patients treated with mycophenolate mofetil (MMF) versus intravenous cyclophosphamide (IVCYC). Methods UK JSLE Cohort Study participants, ≤16 years at diagnosis, with ≥4 American College of Rheumatology criteria for SLE, with class III or IV LN, were eligible. Mann–Whitney U tests, Fisher's exact test and Chi-squared tests were utilized for statistical analysis. Results Of the patients, 34/51 (67%) received MMF, and 17/51 (33%) received IVCYC. No significant differences were identified at 4–8 and 10–14 months post-renal biopsy and last follow-up, in terms of renal British Isles Lupus Assessment Grade scores, urine albumin/creatinine ratio, serum creatinine, ESR, anti-dsDNA antibody, C3 levels and patient/physician global scores. Standardized Damage Index scores did not differ between groups at 13 months or at last follow-up. Inactive LN was attained 262 (141–390) days after MMF treatment, and 151 (117–305) days following IVCYC ( p = 0.17). Time to renal flare was 451 (157–1266) days for MMF, and 343 (198–635) days for IVCYC ( p = 0.47). Conclusion This is the largest study to date investigating induction treatments for proliferative LN in children, demonstrating comparability of MMF and IVCYC.

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Andres Ribas ◽  
Isabel Galcerán ◽  
Sara Outón ◽  
Tarek Salman ◽  
Clara Barrios ◽  
...  

Abstract Background and Aims Lupus Nephritis (LN) is a severe complication of Systemic Lupus Erytemathosus (SLE). This is the main reason why identifying predisposing factors to differentiate patients at risk of developing LN is so important. Method Retrospective study of patients with SLE diagnosed between years 2008-2018 in our center. Demographic, clinical and analytical data have been collected. Results We included 171 patients, 48 (28%) with diagnose of LN. Age at diagnose of SLE was 39,51 ± 15,40 years, being more frequent in women 151 (87,5%). Time of follow-up since SLE diagnose until development of LN was of 3 ± 5, 3 years. Respectful to the LN classification we found: 4 (8%) class I LN, 6 (12.5%) class II LN, 15 (31.2%) class III LN, 19 (39.5%) class IV LN and 4 (8%) class V LN. At diagnose of SLE, the following variables, where related to developing LN: CH50 [HR: 1,039; CI (95%): 1,004-1,064; p=0,024], C3 [HR: 1,029; CI (95%): 1,016-1,042; p<0,001, titer of Anti- DNACrithidia [HR: 4,364; CI(95%): 1,26-15,064; p=0,02], AntiSM [HR: 4,634, CI (95%) 1,76-12,17, p=0,002], ACA IgG [HR: 7,5; CI (95%): 2,3 -24,449; p=0,001] and Lupus anticoagulant [HR: 4,97; CI (95%): 1,591-15,533; p=0,006]. Treatment with hidroxicloroquine is a protective factor against developing LN [HR: 0,17; CI (95%): 0,063-0,511; p=0.001]. At diagnose of LN, complement factors and titer of anti-DNA crithidia show a positive correlation when compared to the initial determinations: C3 [r= 0,605 (p<0,001]); C1q [r= 0,861 (p=0,006)]; CH50 [r= 0,981 (p<0,001), anti- DNACrithidia [r= 0,529 (p<0,001)], anti-Sm [r=0.8, )p=0.001)]. Conclusion Consumption of complement factors, high titers of anti-DNAcrithidia, Anti-SM, ACA IgG and Lupus anticoagulant are related to a future LN development at SLE diagnose. Moreover, we see an increase of their titer once we diagnose LN. Otherwise, treatment with hidroxicloroquine seems to be a protective factor.


Lupus ◽  
2020 ◽  
Vol 29 (12) ◽  
pp. 1616-1622
Author(s):  
Maria Francisca Moraes-Fontes ◽  
Ana Carolina Ferreira ◽  
Nuno Riso ◽  
Helena Viana ◽  
Fernanda Carvalho

In this study, we aimed to evaluate long-term patient survival according to demographic data, clinical manifestations of systemic lupus erythematosus (SLE) and previous and current treatments, collected retrospectively. Patient selection required a minimum of four American College of Rheumatology revised criteria for SLE, biopsy-proven lupus nephritis (LN) available for reclassification according to the modified National Institutes of Health proposal for activity and chronicity indices and a minimum follow-up of at least three years since the last renal biopsy. Selection criteria were fulfilled in 25 patients followed for a median of 21 years. Based on the last renal biopsy, an equal number of patients were thus classified as class I/II and IV ( n=8) and class III and V ( n = 4). The mortality rate for LN was 14%. Having ever been diagnosed with glomerulonephritis (GN) type III or type IV but not class IV alone ( p = 0.046), a higher histological chronicity index at the last renal biopsy ( p = 0.022), not attaining renal remission one year after induction therapy ( p = 0.004), end-stage renal disease on dialysis ( p = 0.033) and the extra-renal Systemic Lupus International Collaborating Clinics Damage Index score ( p = 0.017) were all significantly associated with mortality. Our results may provide important clues for strict observation protocols in particular categories of LN patients with long-standing disease.


Rheumatology ◽  
2019 ◽  
Vol 59 (2) ◽  
pp. 281-291 ◽  
Author(s):  
Ronald F van Vollenhoven ◽  
Sandra V Navarra ◽  
Roger A Levy ◽  
Mathew Thomas ◽  
Amy Heath ◽  
...  

AbstractObjectiveThis extension study of the Phase III, randomized, placebo-controlled Belimumab International SLE Study (BLISS)-52 and BLISS-76 studies allowed non-US patients with SLE to continue belimumab treatment, in order to evaluate its long-term safety and tolerability including organ damage accrual.MethodsIn this multicentre, long-term extension study (GlaxoSmithKline Study BEL112234) patients received i.v. belimumab every 4 weeks plus standard therapy. Adverse events (AEs) were assessed monthly and safety-associated laboratory parameters were assessed at regular intervals. Organ damage (SLICC/ACR Damage Index) was assessed every 48 weeks. The study continued until belimumab was commercially available, with a subsequent 8-week follow-up period.ResultsA total of 738 patients entered the extension study and 735/738 (99.6%) received one or more doses of belimumab. Annual incidence of AEs, including serious and severe AEs, remained stable or declined over time. Sixty-nine (9.4%) patients experienced an AE resulting in discontinuation of belimumab or withdrawal from the study. Eleven deaths occurred (and two during post-treatment follow-up), including one (cardiogenic shock) considered possibly related to belimumab. Laboratory parameters generally remained stable. The mean (s.d.) SLICC/ACR Damage Index score was 0.6 (1.02) at baseline (prior to the first dose of belimumab) and remained stable. At study year 8, 57/65 (87.7%) patients had no change in SLICC/ACR Damage Index score from baseline, indicating low organ damage accrual.ConclusionBelimumab displayed a stable safety profile with no new safety signals. There was minimal organ damage progression over 8 years.Trial registrationClinicalTrials.gov, https://clinicaltrials.gov, NCT00424476 (BLISS-52), NCT00410384 (BLISS-76), NCT00732940 (BEL112232), NCT00712933 (BEL112234).


2011 ◽  
Vol 39 (1) ◽  
pp. 79-85 ◽  
Author(s):  
DAISUKE WAKASUGI ◽  
TAKAHISA GONO ◽  
YASUSHI KAWAGUCHI ◽  
MASAKO HARA ◽  
YUMI KOSEKI ◽  
...  

Objective.To determine the frequency of International Society of Nephrology/Renal Pathology Society (ISN/RPS) class III or IV lupus nephritis in patients with systemic lupus erythematosus (SLE) without clinical renal involvement.Methods.We investigated the renal pathology of 195 patients with SLE, including 86 patients without clinical renal involvement.Results.Lupus nephritis other than class I was found in 58% of the patients without clinical renal involvement, and class III and IV nephritis was found in 15% of these patients. To reveal the predictive measures involved in class III or IV lupus nephritis, we explored the clinical measures in patients with SLE who did not have clinical renal involvement. Anti-dsDNA antibody titers were significantly higher (p = 0.0266) and C3 values were significantly lower (p = 0.0073) in patients with class III or IV lupus nephritis than in patients without class III or IV lupus nephritis. The sensitivity and specificity values were 77% and 73%, respectively, for cutoff levels of both 40 IU/ml for anti-dsDNA antibodies and 55 mg/dl for C3 (OR 8.8, p = 0.0011).Conclusion.The frequency of nephritis, including ISN/RPS class III and IV, was unexpectedly high in SLE patients without clinical renal involvement. ISN/RPS class III or IV lupus nephritis could be hidden in patients with SLE who present both a high titer of anti-dsDNA antibody and a low concentration of C3, even when they have clinically normal urinary findings and renal function.


2020 ◽  
Vol 9 (2) ◽  
pp. e14-e14
Author(s):  
Eman Hassan Abdelbary ◽  
Noha Farouk Ahmed ◽  
Adel Abdelmohsen Ghorab

Introduction: Lupus nephritis (LN) is a substantial manifestation of systemic lupus erythematosus (SLE). HDAC6 is overexpressed in various kidney diseases, and its inhibition slows kidney injury progression. Urinary TFF3 increases in chronic kidney diseases (CKDs) and may be associated with patient’s outcome. Objectives: This study aimed to examine the relationship between renal HDAC6 and TFF3 proteins expression and with clinicopathologic characteristics and outcome of LN. Patients and Methods: HDAC6 and TFF3 proteins’ expression was immunohistochemically detected in 56 cases of LN. They were correlated to patients’ age, gender, urinary 24 hours protein and serum creatinine levels at baseline and during follow up. Additionally, they were correlated to LN classes, activity index (AI) and chronicity index (CI) and relapse free survival (RFS). Results: HDAC6 overexpression was significantly associated with serum creatinine and 24 hours proteinuria levels at baseline (P = 0.041 and P =0.026 respectively) and during follow up (P < 0.001). It was associated with AI and CI of class III and IV LN (P = 0.047 and 0.003 respectively). TFF3 overexpression was associated with higher serum creatinine and more proteinuria at baseline (P = 0.015 and 0.001 respectively) and during follow up (P < 0.001). It was significantly associated with higher CI (P = 0.001). Both markers were associated with shorter RFS (P < 0.001). Conclusion: HDAC6 and TFF3 proteins are associated with clinicopathologic features of renal damage in LN. They are reliable predictors of patients’ RFS, which makes them good candidates for risk stratification of patients and targeted therapy.


2021 ◽  
Author(s):  
Panagiotis Athanassiou ◽  
Lambros Athanassiou ◽  
Ifigenia Kostoglou-Athanassiou

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease. It is characterized by a variable clinical course ranging from mild to fatal disease. It can affect the kidneys. The aim of treatment in SLE is the prevention of flares and the prevention of accumulation of damage to the main organs affected as well as the prevention of drug side effects. The cornerstone of SLE treatment is hydroxychloroquine. Corticosteroids are used both as induction treatment in disease flares as well as in small doses as maintenance treatment. Immunosuppressants, such as azathioprine, methotrexate and mycophenolate mofetil are used as steroid sparing agents. Calcineurin inhibitors, namely tacrolimus and cyclosporin A may also be used as immunosuppressants and steroid sparing agents. Pulse methylprednisolone, along with mycophenolate mofetil and cyclophosphamide are used as induction treatment in lupus nephritis. Rituximab, an anti-CD20 biologic agent may be used in non-renal SLE. In patients insufficiently controlled with hydroxychloroquine, low dose prednisone and/or immunosuppressive agents, belimumab may be used with beneficial effects in non-renal disease and lupus nephritis.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 305.2-306
Author(s):  
F. Faustini ◽  
H. Idborg ◽  
E. Svenungsson ◽  
S. Poetzsch ◽  
S. Okitsu ◽  
...  

Background:Lupus nephritis (LN) represents a serious manifestation of systemic lupus erythematosus (SLE) which requires timely diagnosis, treatment and monitoring. Kidney biopsy is the gold standard of diagnosis and is instrumental to treatment decisions, however it is not generally performed for monitoring and evaluation of response to treatment. To such purposes, accessible biomarkers, for instance urinary, might be highly advantageous.Objectives:To evaluate urine-Galectin 3 binding protein (uGAL3BP) as a novel biomarker in biopsy-proven active lupus nephritis (A-LN) in comparison to active non-renal SLE (ANR-SLE), inactive SLE (I-SLE), and in population-based controls (HC). Furthermore, we compared uGAL3BP with known markers of renal pathology including neutrophil gelatinase-associated lipocalin (NGAL), osteopontin (OPN), kidney injury molecule 1 (KIM-1), and galectin 3 (GAL3).Methods:Urine samples from A-LN (n=86), ANR-SLE (n=63), I-SLE (n=73) and HC (n=48) were included. uGAL3BP was measured using a commercial ELISA kit and values, adjusted for u-creatinine levels, were expressed as ng/mmol. Other markers analyzed according to clinical routine at the Department of Clinical Chemistry at Uppsala University Hospital were also adjusted for u-creatinine levels. Renal biopsies were graded according to the ISN/RPS classification(1) and evaluated for activity and chronicity index. Ten A-LN patients were evaluated before and after induction treatment.Results:In the A-LN group, median (IQR) levels of u-GAL3BP were 15.8 (6.8-24.6) ng/mmol, while in ANR-SLE, I-SLE, HC were significantly lower 4.4 (2.0-9.0), 2.8 (1.7-4.7), 2.0 (0.9-4.8) respectively (Kruskal-Wallis p<0.0001). Similarly, u-NGAL was found at higher levels in A-LN patients, 3.3 (2.0-5.7) μg/mmol, with respect to the ANR-SLE 2.0 (0.9-4.5), I-SLE 1.6 (0.8-3.2), and HC 2.4 (1.2-5.3), (p=0.008). The highest levels of OPN were found in the group of I-SLE (190.6 (85.1-299.9) μg/mmol, compared to A-LN 72.98 (37.6-118.1), ANR-SLE 92.3 (58.5-129.7) and HC 76.5 (58.2-120.3), (p<0.0001). KIM-1 levels differed among groups with higher levels in the A-LN group (188.9 (113.7-309.7) ng/mmol), in comparison to ANR-SLE 131.4 (92.2-186.1), I-SLE 123.8 (70.3-200.2), and HC 78.2 (68.8-115.1), (p<0.0001). GAL3 showed comparable levels across groups.When exploring the biomarkers across histologic subgroups of LN, u-GAL3BP could discriminate between proliferative and mesangial forms (17.7(9.6-32.5) vs 6.7(5.1-16.1) ng/mmol, p=0.027), while it did not discriminate against membranous LN. U-NGAL was higher in proliferative LN 3.7(2.4-5.8) µg/mmol with respect to membranous 2.4 (1.1-3.8) (p=0.01), while mesangial LN showed comparable levels. OPN, KIM-1 and GAL3 were comparable across groups.In the ten patients with available samples after induction therapy (mycophenolate mofetil (MMF) in 4, rituximab (RTX) in one, cyclophosphamide in 5 (one combined with MMF and one with RTX), u-GAL3BP showed a significant decrease of median levels from 218.8 to 41.5 ng/mmol (Wilcoxon p=0.03). u-GAL3BP associated with renal activity in class III/IV LN (R=0.42, p=0.004).Conclusion:Among the tested markers, high uGal3BP adjusted for creatinine was found to be a promising marker of renal involvement in SLE patients and associated with renal activity in patients with proliferative forms (class III/IV) of LN. A decrease was further seen following therapy, suggesting that u GAL3-BP could be used to monitor renal activity.References:[1]Weening JJ, D’Agati VD, Schwartz MM, Seshan SV, Alpers CE, Appel GB, et al. The classification of glomerulonephritis in systemic lupus erythematosus revisited. J Am Soc Nephrol. 2004;15(2):241-50.[2]Houssiau FA, Vasconcelos C, D’Cruz D, Sebastiani GD, Garrido Ed Ede R, Danieli MG, et al. Immunosuppressive therapy in lupus nephritis: the Euro-Lupus Nephritis Trial, a randomized trial of low-dose versus high-dose intravenous cyclophosphamide. Arthritis Rheum. 2002;46(8):2121-31.Disclosure of Interests:Francesca Faustini Speakers bureau: I have received speaking fees, last time more than two years ago, Helena Idborg: None declared, Elisabet Svenungsson: None declared, Sven Poetzsch Employee of: Merck Serono, Shinji Okitsu Employee of: Merck Serono, Anders Larsson: None declared, Iva Gunnarsson: None declared


Lupus ◽  
2018 ◽  
Vol 27 (8) ◽  
pp. 1358-1362 ◽  
Author(s):  
D Jesus ◽  
M Rodrigues ◽  
J A P da Silva ◽  
L Inês

Standard induction therapy for lupus nephritis (LN) with mycophenolate mofetil (MMF) or cyclophosphamide (CYC) is often ineffective. Evidence on rescue induction regimens is scarce. We analyzed efficacy and tolerability of multitarget immunosuppression with MMF and cyclosporine A (CsA) as induction treatment for LN (class III/IV/V) refractory to CYC and/or MMF. We included all six refractory LN patients (class IV = 3, class V = 2, class III = 1) from our 400-patient tertiary Lupus Clinic observed between 2012 and 2015. Four patients had previously received pulse CYC. All six received MMF as first or second induction therapy and CsA was added once failure to reach remission was established. Daily dose of MMF was 2–3 g and CsA was dosed up to 2.6–3.7 mg/kg/day. Mean proteinuria was reduced from 2407 mg/24 hours at the start of the MMF+CsA regimen to 544 mg/day after six months. The mean prednisolone dose was reduced from 17.5 to 6 mg/day after six months of MMF+CsA. Four patients achieved a complete renal response, one patient had a partial renal response and one failed to respond. None of the patients presented with adverse events. These data suggest that adding CsA to MMF can induce complete remission of refractory LN and is well tolerated.


1970 ◽  
Vol 5 (2) ◽  
pp. 8-13
Author(s):  
M Mostafi ◽  
MG Rabbani ◽  
MR Hossain ◽  
AR Siddiqui ◽  
SB Rabbani

Class IV Lupus Nephritis is a difficult medical situation requiring aggressive management. Many patients do not respond to conventional cyclophosphamide (CPM) therapy. The aim of this study was to evaluate the effect of cyclosporine (CsA) and mycophenolate mofetil (MMF) in the treatment of CPM refractory class IV Lupus nephritis. The study was conducted at Combined Military Hospital (CMH) and Cantonment General Hospital (CGH) of Dhaka over a period of 8 years (from January 2000 till December 2008). CPM refractory Class IV Lupus nephritis patients were randomly assigned into 2 groups cyclosporine (4mg/kg/day) and mycophenolate mofetil (1000-2000mg/day). Thirty one patients completed at least one year follow up and were included in the study. Sixteen patients were included in cyclosporine group and 15 patients in mycophenolate mofetil group. CsA treated patients had a remission rate of 87.5% which was 80% in MMF group. The average remission time was 16.21 weeks in CsA and 20.91 weeks in MMF group. The urinary total protein(UTP) and creatinine clearance (CCr) values  were  similar in both groups, 0.54 gm vs 0.66 gm & 81 vs 86 ml/min. The systemic lupus erythematosus disease activity index (SLEDAI) was 9.56 and 9.2 in CsA and MMF group which came down to 1.92 and 1.83 in the same groups after remission. In this study It was found that both cyclosporine and mycophenolate mofetil were very effective in the treatment of CPM refractory class IV Lupus nephritis with slight better response with cyclosporine. Key words: Lupus Nephritis, mycophenolate mofetil, cyclosporine. DOI: 10.3329/jafmc.v5i2.4575 JAFMC Bangladesh Vol.5(2) (December) 2009, pp.8-13


2021 ◽  
Author(s):  
Ho SO ◽  
Evelyn CHOW ◽  
Isaac T Cheng ◽  
Sze-Lok LAU ◽  
Tena K Li ◽  
...  

Abstract Background Telemedicine has become an essential tool to manage patients with chronic disease during the COVID-19 pandemic in many parts of the world, and its widespread use will likely go beyond the outbreak. However, there is no study examining the factors associated with telemedicine use for follow-up of patients with SLE.Methods Consecutive patients followed up at the lupus nephritis clinic were contacted for their preference in changing the coming consultation to telemedicine in the form of videoconferencing. The demographic, socioeconomic and disease data of the first 140 patients opted for telemedicine and 140 control patients preferred to continue standard in-person follow-up were compared. Results The mean age of the 280 recruited patients was 45.6 ± 11.8 years. The mean disease duration was 15.0 ± 9.2 years. The majority of them had lupus nephritis class III, IV or V (88.2%) and were on prednisolone (90%). Three quarters of the patients (67.1%) were on immunosuppressants. The mean SLEDAI-2k was 4.06 ± 2.54, physician global assessment (PGA) was 0.46 ± 0.62 and SLICC/ACR damage index was 1.11 ± 1.36. A significant proportion of the patients (72.1%) had one or more comorbidities. It was found that patients with higher mean PGA (telemedicine: 0.54±0.63 vs control: 0.38±0.59, p=0.025) and family monthly income > USD3, 800 (telemedicine: 51/140, 36.4% vs control: 33/140, 23.6%; p=0.028) preferred telemedicine, while full-time employees (telemedicine: 56/140, 40.0% vs control: 71/140, 50.7%; p=0.041) preferred in-person follow-up. These predictors remained significant after controlling for age in the multivariate analysis. PGA was positively correlated with the perception that TM could reduce and routine visit could increase the risk of COVID-19 during the outbreak. No other clinical factors were found to be associated with the preference of telemedicine follow-up. Conclusions When choosing the mode of care delivery between telemedicine and physical clinic visit for patients with SLE, the subjective disease activity as well as patient’s employment and economic status appeared to be important.


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