Successful therapeutic response with sequential therapy of rituximab and belimumab in a hispanic patient with refractory lupus nephritis

2021 ◽  
Vol 13 (4) ◽  
pp. 65-68
Author(s):  
Vinicki JP ◽  
Daza JL,2 ◽  
Nadal MA

Lupus nephritis (LN) is the most common severe organ manifestation of systemic lupus erythematosus (SLE). Life expectancy and renal survival is reduced in these patients. A partial remission in LN is associated with a significantly better patient and renal survival rate compared with no remission. We report the case of a 27-year-old Hispanic patient with diffuse proliferative lupus nephritis (grade IV with high activity index) managed with induction therapy with mycophenolate mophethyl (MMF, 1000 mg daily escalating to 3000 mg daily and prednisone (PDN) 1 mg/kg/day. Progression of proteinuria with preserved renal function and extra-renal activity were observed (alopecia). Re-induction with IV cyclophosphamide (CYC, 1 gr.) and pulse IV methylprednisolone (500 mg for three days) was administered, followed by a lower starting dose of PDN (0.5 mg/kg/day). Treatment failure was observed. A second renal biopsy evidenced renal damage (chronicity index 4/12 and activity index 4/24). The patient also developed non-renal clinical manifestations (malar rash, oral ulcers and arthritis). Treatment with IV rituximab (RTX) 1000 mg X2 associated with MMF 1000 mg per day and IV methylprednisolone 500 mg X3 was initiated, followed by PDN 0.5 mg/kg/day with a dose-tapering scheme similar to CYC re-induction. Treatment continued with IV Belimumab (BLM) 600 mg every month associated with MMF 1000 mg per day. Sequential therapy with RTX + BLM showed a partial renal and complete extra-renal response in a patient with severe lupus despite two 2 immunosuppressive treatment schemes.

2018 ◽  
pp. 52-58
Author(s):  
Le Thuan Nguyen ◽  
Bui Bao Hoang

Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple organ systems. The kidney appears to be the most commonly affected organ, especially nephrotic is a serious kidney injury. The clinical, laboratory manifestations and histopathology are very useful for diagnosis, provide the means of predicting prognosis and guiding therapy in nephrotic patients with lupus nephritis. Methods: Descriptive cross-sectional study of nephrotic patients with lupus treated in the Department of Nephrology Trung Vuong Hospital and Cho Ray Hospital between May/2014 and May/2017. Renal histopathological lesions were classified according to International Society of Nephrology/Renal Pathology Society - ISN/RPS ’s 2003. The clinical, laboratory manifestations and histopathological features were described. Results: Of 32 LN with nephritic range proteinuria cases studied, 93.7% were women. The 3 most common clinical manifestations were edema (93.8%), hypertension (96.8%) and pallor (68.9%), musculoskeletal manifestions (46.9%), malar rash (40.6%). There was significant rise in laboratory and immunological manifestions with hematuria (78.1%), Hb < 12g/dL (93.5%), increased Cholesterol (100%), and Triglycerid (87.5%), Creatinine > 1.4 mg/dL (87.5%), increased BUN 71.9%, ANA (+) 93.8%, Anti Ds DNA(+) 96.9%, low C3: 96.9%, low C4: 84.4%. The most various and severe features were noted in class IV with active tubulointerstitial lesions and high activity index. Conclusion: Lupus nephritis with nephrotic range proteinuria has the more severity of histopathological feature and the more severity of the more systemic organ involvements and laboratory disorders were noted. Key words: Systemic lupus, erythematosus (SLE) lupus nepphritis, clinical


Lupus ◽  
2020 ◽  
Vol 29 (6) ◽  
pp. 607-616
Author(s):  
Asmaa SM Abdel-Rehim ◽  
Nesrine A Mohamed ◽  
Marwa M Shakweer

Background Lupus nephritis (LN) is an ominous manifestation of systemic lupus erythematosus (SLE). Clinical renal affection is present in about 70% of lupus patients, and more patients have histological evidence of renal involvement without clinical manifestations. This study aimed to investigate the potential role of serum interleukin-34 (IL-34) as an early marker for the detection of silent LN. Methods Thirty-three lupus patients with silent LN (group I), 37 patients with clinical LN (group II) and 20 controls were included. The SLE Disease Activity Index (SLEDAI), IL-34, anti-dsDNA antibodies and renal biopsy were assessed in all patients. Results Serum IL-34 levels were significantly higher in all lupus patients compared to healthy controls ( p < 0.001) and showed a significant positive correlation with SLEDAI score. SLE patients with positive anti-dsDNA antibodies had more active disease according to SLEDAI and higher levels of IL-34 than those with negative anti-dsDNA antibodies. In both studied groups, serum IL-34 levels were significantly higher in patients with proliferative LN (class III and class IV) than those with non-proliferative lupus (class II and class V) and controls. Yet, in both groups, IL-34 was not useful in differentiating active from chronic renal affection. Conclusion In lupus patients with insignificant proteinuria, serum levels of IL-34 distinguished the different histological classes of subclinical LN. Serum IL-34 may be used as a surrogate marker for early renal affection in silent LN, especially the proliferative type.


Lupus ◽  
2020 ◽  
Vol 29 (13) ◽  
pp. 1800-1806
Author(s):  
Sujata Ganguly ◽  
Sanjukta Majumder ◽  
Sandeep Kumar ◽  
Ranjan Gupta ◽  
Hafis Muhammed ◽  
...  

Introduction Complement activation is central to the pathogenesis of lupus nephritis (LN). Low serum complement C3 and C4, are traditionally used as markers of lupus disease activity in general and LN in particular. In this study we prospectively measured plasma and urine C3d and C4d, degradation products of C3 and C4 corrected to creatinine in a cohort of biopsy proven LN in a longitudinal fashion for its correlation with disease activity. Methods Twenty eight biopsy proven active lupus nephritis (AN) were recruited along with four inactive nephritis (IN) and 10 healthy controls (HC). Plasma and urine were collected at baseline, prior to induction treatment and 3 months later. Clinical measures of disease activity, Systemic lupus erythematosus disease activity index 2000 (SLEDAI 2K), renal SLEDAI, serum C3, C4 and antibodies to ds DNA, urine protein and creatinine excretion (UP/UC) were collected. Plasma and urine C3d and C4d were measured using ELISA and normalized to spot urine creatinine value. Results Twenty eight AN of median age of 26.5 (20–31.50) years and disease duration of 3 (0.7–5) years were enrolled. The median urinary C3d/creatinine before treatment was 388.20 (48.98–1296) ng/mg which fell significantly to 62.69 (28.04–502.4) ng/mg at 3 months followup (p-0.01). The baseline values for the active renal disease was significantly different from IN group (9.9 (4.5–46.53 ng/mg) p-0.00). Treatment responders (partial and complete) at 6 months showed a significant fall in urinary C3d at 3 months whereas non responders had a non significant change in value. There was a significant correlation of urine C3d/creatinine with SLEDAI2K (r-0.433, p-0.00), renal SLEDAI (r-0.356, p-0.00), UP/UC ratio (r-0.489, p-<0.0001) but no significant correlation with C3 or C4. There was a significant fall in the median values of plasma C3d from 791.1 (516.0.00–1550.43) µg/ml to 338.52 (211.35–525.82) (p-0.00) µg/ml at the end of 3 months. The values showed a significant correlation with SLEDAI 2K, renal SLEDAI, UP/UC along with a significant negative correlation with C3 and C4. Conclusion Urinary C3d/creatinine levels and plasma C3d levels can be used as biomarker of disease activity and treatment response.


2018 ◽  
Vol 77 (9) ◽  
pp. 1318-1325 ◽  
Author(s):  
Gabriella Moroni ◽  
Paolo Gilles Vercelloni ◽  
Silvana Quaglini ◽  
Mariele Gatto ◽  
Davide Gianfreda ◽  
...  

ObjectivesTo evaluate changes in demographic, clinical and histological presentation, and prognosis of lupus nephritis (LN) over time.Patients and methodsWe studied a multicentre cohort of 499 patients diagnosed with LN from 1970 to 2016. The 46-year follow-up was subdivided into three periods (P): P1 1970–1985, P2 1986–2001 and P3 2002–2016, and patients accordingly grouped based on the year of LN diagnosis. Predictors of patient and renal survival were investigated by univariate and multivariate proportional hazards Cox regression analyses. Survival curves were compared using the log-rank test.ResultsA progressive increase in patient age at the time of LN diagnosis (p<0.0001) and a longer time between systemic lupus erythematosus onset and LN occurrence (p<0.0001) was observed from 1970 to 2016. During the same period, the frequency of renal insufficiency at the time of LN presentation progressively decreased (p<0.0001) and that of isolated urinary abnormalities increased (p<0.0001). No changes in histological class and activity index were observed, while chronicity index significantly decreased from 1970 to 2016 (p=0.023). Survival without end-stage renal disease (ESRD) was 87% in P1, 94% in P2% and 99% in P3 at 10 years, 80% in P1 and 90% in P2 at 20 years (p=0.0019). At multivariate analysis, male gender, arterial hypertension, absence of maintenance immunosuppressive therapy, increased serum creatinine, and high activity and chronicity index were independent predictors of ESRD.ConclusionsClinical presentation of LN has become less severe in the last years, leading to a better long-term renal survival.


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 ◽  
...  

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.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1519.2-1519
Author(s):  
D. J. Park ◽  
S. E. Choi ◽  
H. Xu ◽  
J. H. Kang ◽  
S. S. Lee

Background:Recent studies have shown that the simultaneous positivity of anti-double stranded DNA, -nucleosome, and -histone antibodies (3-pos) is prevalent in lupus nephritis (LN) patients compared to non-renal systemic lupus erythematosus (SLE) patients.Objectives:The aim of this study was to define the clinical, biologic, histopathologic, and prognostic differences according to the simultaneous reactivity to those antibodies in Korean patients with biopsy-proven LN.Methods:We studied 102 patients who underwent kidney biopsy prior to the start of induction treatment and who were subsequently treated with immunosuppressives and followed-up for more than 12 months. Sociodemographic, clinical, laboratory, and treatment-related data at the time of kidney biopsy and during follow-up were obtained by a review of patients’ charts. Antibodies were detected by immunoblot analysis or ELISA at the time of renal biopsy.Results:Fifty-eight (35.4%) of the total of 102 LN patients had 3-pos. In comparison with non-3-pos patients, the patients with 3-pos showed a higher SLE Disease Activity Index-2000 score (P=0.002), lower lymphocyte level (p=0.004), higher proportion of proteinuria >3.5 g/24 hr (p=0.005), and higher positivity of urinary sediments (p=0.005) at the time of renal biopsy. In the renal histopathologic findings, the patients with 3-pos had more proliferative LN (p=0.015) and also showed more endocapillary hypercellularity, sub-endothelial hyaline deposits, fibrinoid necrosis/karyorrhexis, and cellular crescents in the disease activity index (p=0.016, p=0.045, p=0.002, and p=0.022, respectively), as well as a higher activity score (p=0.011). After a median follow-up of 83.2 months, rapid glomerular filtration rate decline was frequently observed in patients with 3-pos compared to those without (p=0.012).Conclusion:Our findings suggest that 3-pos is related to severe LN and, furthermore, that patients with 3-pos show a rapid decline of renal function compared to those without.Disclosure of Interests:None declared


Lupus ◽  
2019 ◽  
Vol 28 (6) ◽  
pp. 748-754 ◽  
Author(s):  
R C Li ◽  
J Guo ◽  
L C Su ◽  
A F Huang

Objective This study aimed to assess IL-24 levels and their association with clinical manifestations in patients with systemic lupus erythematosus (SLE). Methods There were 75 patients with SLE and 58 healthy controls recruited in this study. Serum levels of IL-24 were measured by enzyme-linked immunosorbent assays, and mRNA levels of IL-24 were tested by quantitative real-time polymerase chain reaction . The area under the curve of the receiver operating characteristic (ROC) curve was used for diagnostic ability of the inflammatory cytokine. Results Serum IL-24 levels were significantly higher in SLE patients than that in healthy controls. SLE patients with nephritis had higher IL-24 levels than those without nephritis. Active SLE patients showed higher expression of IL-24 as compared to less active disease patients. The mRNA levels of IL-24 were much higher in SLE patients. Correlation analysis showed significant correlation between serum IL-24 levels and SLE disease activity index. In addition, ROC analysis may suggest good ability of serum IL-24 in differentiating SLE. Conclusion The inflammatory cytokine correlated with SLE disease activity, and may be involved in this disease pathogenesis.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1403.2-1403
Author(s):  
L. Bohmat ◽  
N. Shevchenko ◽  
I. Bessonova

Background:Lupus nephritis is the most severe and adverse systemic lupus erythematosus (SLE) syndrome. According to modern recommendations, the clinical manifestations of active nephritis should be taken under medical control in 6 months after the start of the disease’s treatment1.Objectives:The aim of this study was to examine the functional status of the kidneys in children with SLE in the course of the disease for more than one year.Methods:The analysis included case histories of 43 patients with SLE, mostly females (41), aged 7 to 18 years (mean age 14.4 years) with disease duration of 4.75 ± 0.58 years of whom 22 were less than three years, 21 - more than three years. All children received corticosteroid therapy, at the time of the examination the average dose was 13.85 ± 1.86 mg per day in terms of prednisolone. The second component of therapy was azathioprine (average dose 97.61 ± 2.11 mg). All children received hydroxychloroquine (5 mg/kg per day).To determine the functional state of the kidneys a clinical analysis of urine, a study of the scope of specific gravity of urine during the day (Zymnytsky test), the content of creatinine and urea in serum to determine the glomerular filtration rate (GFR), the level of microalbuminuria per day were evaluated.Results:Renal involvement in the developed SLE occurred in 73.08% of patients. Among them, therapy during the first 6 months was considered quite effective in 58.06% of patients. It was found that in children with disease duration from one to three years proteinuria was registered in 68.18%, a decrease in GFR in 4.45% and hyperfiltration in 9.09%. In the group of children with duration of SLE more than three years revealed deeper changes in renal function; there was proteinuria in 90.47%, the frequency of GFR decreased was in 19.04%, a decrease of renal concentration function was in 14.28% of cases.Indicators of renal function in children with SLE depending on the duration of the disease (M ± m)IndicatorDuration of the diseasefrom 1 year to 3 years n = 22over 3 yearsn = 21Creatinine, mmol/l0,080 ± 0,0140,090 ± 0,018Мочевина, mmol/l5,66 ± 1,425,63 ± 1,61GFR, ml/min117,05 ± 19,68100,20 ± 18,98 *Microalbuminuria, mg/day24,41 ± 13,1334,73 ± 24,76Density min1,007 ± 0,0051,006 ± 0,005Density max1,024 ± 0,0051,019 ± 0,005 ***р<0,03;**р<0,01 the probability of differences when comparing between groupsConclusion:Long-term follow-up of children with SLE over one year reveals a prolongation of renal dysfunction, which worsens after three years, and is the basis for the development of irreversible renal impairment.References:[1]European evidence-based recommendations for the diagnosis and treatment of childhood-onset lupus nephritis: the SHARE initiative /Noortje Groot, Nienke de Graeff, Stephen D Marks et all. //Ann Rheum Dis. 2017 Dec;76(12):1965-1973.Disclosure of Interests:None declared


2014 ◽  
Vol 54 (6) ◽  
pp. 338
Author(s):  
Lukman Oktadianto ◽  
Risky Vitria Prasetyo ◽  
Ninik Asmaningsih Soemyarso ◽  
Mohammad Sjaifullah Noer

Background Renal involvement during the clinical course ofsystemic lupus erythematosus (SLE) is generally considered to bethe most important factor influencing disease prognosis in termsof morbidity and mortality. Various factors have been reported toinfluence the prognosis of lupus nephritis (LN).Objective To analyze clinical signs and laboratory parameters thatmight serve as predictors associated with mortality in pediatricLN.Methods Retrospectively, medical records of children with LNat Soetomo Hospital from 1998 to 2011 were studied. Diagnosisof SLE was based on Revised American Rheumatism Associationcritera, while patients with clinical manifestations of hypertension,abnormal urinalysis, and serum creatinin > 1 mg/dL wereconsidered as lupus nephritis. Cox proportional hazard modelingwas used to assess for associations of clinical signs and laboratoryparameters with mortality. Kaplan-Meier survival analysis wasused to assess the cumulative survival from the time of diagnosisto the outcome.Results There were 57 children with LN of whom 43 (75%) weregirls. The female-to-male ratio was 3:1. Subjects’ mean age was 10.6(SD 6.87) years. The mean time of observation was 51 (SD 74.54)months and 23 (40%) children died. Age, gender, hypertension,hematuria, proteinuria, and anemia were not significant aspredictors for mortality. However, hypertensive crisis (HR=2.79;95%CI 1.16 to 6.75; P=0.02) and initial glomerular filtration rate(GFR) of <75 mL/min/1.73m2 (HR=3.01; 95%CI 1.23 to 7.34;P=0.01) were significant predictors of mortality in children with LN.The mean survival time of LN with hypertensive crisis and initialGFR <75 mL/min/1.73m2 was 36.9 (SD 12.17) months.Conclusion Hypertensive crisis and GFR <75 mL/min/1.73m2 aresignificant predictors of mortality in children with LN.


2021 ◽  
Vol 10 (20) ◽  
pp. 4654
Author(s):  
Tsu-Yi Hsieh ◽  
Yi-Ching Lin ◽  
Wei-Ting Hung ◽  
Yi-Ming Chen ◽  
Mei-Chin Wen ◽  
...  

Background: Lupus nephritis (LN) often lead to end-stage renal disease in systemic lupus erythematosus patients. This study aimed to investigate the clinical application of renal gallium-67 scans for determining renal histological parameters in LN patients. Methods: Between 2006 and 2018, 237 biopsy-proven and 35 repeat biopsies LN patients who underwent renal gallium scans before or after biopsy were included for analysis. The classification and scoring of LN were assessed according to the International Society of Nephrology/Renal Pathology Society. A delayed 48-h gallium scan was performed and interpreted by semiquantitative methods using left kidney/spine (K/S) ratio. The renal histological results were compared with gallium uptake. Results: Out of 237 participants, 180 (76%) had proliferative LN. Baseline gallium left K/S ratio was significantly higher in class IV LN as compared to class III (median (interquartile range, IQR): 1.16 (1.0–1.3), 0.95 (0.9–1.1), respectively, p < 0.001). Furthermore, changes in gallium uptake between two biopsies were positively correlated with changes activity index (r = 0.357, p = 0.035), endocapillary hypercellularity (r = 0.385, p = 0.032), and neutrophils infiltration (r = 0.390, p = 0.030) in renal pathology. Conclusions: Renal gallium uptake is associated with active inflammation in LN. Changes in renal gallium uptake positively correlated with changes in activity index in renal pathology.


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