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1.
Medicine (Baltimore) ; 100(9): e24887, 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33655949

RESUMO

RATIONALE: Membranous glomerulonephritis (MN) is the leading cause of nephrotic syndrome in adults and is classified as primary or secondary. Secondary MN accounts for 20% to 30% of all MN cases and can arise from a number of conditions, including autoimmune diseases. Recently exostosin 1/exostosin 2 (EXT1/EXT2) have been identified as the common antigens in secondary autoimmune MN and are present in cases of pure membranous lupus nephritis (LN). The treatment of EXT1/EXT2-associated MN remains elusive. PATIENT CONCERNS: We present the case of a 15-year-old female who presented with nephrotic syndrome, positive ANA and dsDNA, and low serum complements. A renal biopsy revealed pure membranous nephritis with IgG and C3 deposition. EXT1 was found along the glomerular capillary walls and stained positive, while phospholipase A2 receptor (PLA2R) and thrombospondin type-1 domain-containing 7A (THSD7A) were negative. DIAGNOSIS: The patient was diagnosed with ETX1-associated membranous LN. INTERVENTIONS: She was treated with prednisone and multiple low-dose rituximab (4 200 mg doses, approximately every 2 months, based on CD19+ cells counts). OUTCOMES: The patient had complete remission within 8 months later, and she remained in remission for the 16-month period of follow-up. LESSONS: To our knowledge, this is the first case of EXT1-associated MN that has been successfully treated by multiple low-dose rituximab. Further studies can investigate the optimal dosage and treatment protocol.


Assuntos
Autoanticorpos/imunologia , Nefrite Lúpica/tratamento farmacológico , N-Acetilglucosaminiltransferases/imunologia , Rituximab/administração & dosagem , Adolescente , Autoanticorpos/metabolismo , Biomarcadores/metabolismo , Biópsia , Relação Dose-Resposta a Droga , Feminino , Humanos , Fatores Imunológicos/administração & dosagem , Glomérulos Renais/patologia , Nefrite Lúpica/imunologia , Nefrite Lúpica/metabolismo , N-Acetilglucosaminiltransferases/metabolismo
2.
Rheumatology (Oxford) ; 60(3): 1474-1479, 2021 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-33677595

RESUMO

OBJECTIVES: We aimed to estimate what proportion of people with SLE attending UK rheumatology clinics would be categorized as being at high risk from coronavirus disease 2019 (COVID-19) and therefore asked to shield, and explore what implications this has for rheumatology clinical practice. METHODS: We used data from the British Society for Rheumatology multicentre audit of SLE, which included a large, representative cross-sectional sample of patients attending UK Rheumatology clinics with SLE. We calculated who would receive shielding advice using the British Society for Rheumatology's risk stratification guidance and accompanying scoring grid, and assessed whether ethnicity and history of nephritis were over-represented in the shielding group. RESULTS: The audit included 1003 patients from 51 centres across all 4 nations of the UK. Overall 344 (34.3%) patients had a shielding score ≥3 and would have been advised to shield. People with previous or current LN were 2.6 (1.9-3.4) times more likely to be in the shielding group than people with no previous LN (P < 0.001). Ethnicity was not evenly distributed between the groups (chi-squared P < 0.001). Compared with White people, people of Black ethnicity were 1.9 (1.3-2.8) and Asian 1.9 (1.3-2.7) times more likely to be in the shielding group. Increased risk persisted after controlling for LN. CONCLUSION: Our study demonstrates the large number of people with SLE who are likely to be shielding. Implications for clinical practice include considering communication across language and cultural differences, and ways to conduct renal assessment including urinalysis, during telephone and video consultations for patients who are shielding.


Assuntos
/prevenção & controle , Lúpus Eritematoso Sistêmico/terapia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Quarentena/estatística & dados numéricos , Reumatologia/estatística & dados numéricos , Adulto , Estudos Transversais , Feminino , Humanos , Lúpus Eritematoso Sistêmico/virologia , Nefrite Lúpica/terapia , Nefrite Lúpica/virologia , Masculino , Auditoria Médica , Pessoa de Meia-Idade , Análise de Regressão , Telemedicina/estatística & dados numéricos , Reino Unido/epidemiologia
3.
Medicine (Baltimore) ; 100(11): e24423, 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33725933

RESUMO

ABSTRACT: The association between Glutathione S-transferase Pi 1(GSTP1) genetic polymorphism (rs1695, 313A>G) and cyclophosphamide-induced toxicities has been widely investigated in previous studies, however, the results were inconsistent. This study was performed to further elucidate the association.A comprehensive search was conducted in PubMed, Embase, Web of Science, China National Knowledge Infrastructure, and Wan Fang database up to January 5, 2020. Risk ratios (RRs) and 95% confidence intervals (95% CIs) were used to estimate the association between GSTP1 rs1695 polymorphism and cyclophosphamide-induced hemotoxicity, gastrointestinal toxicity, infection, and neurotoxicity.A total of 13 studies were eventually included. Compared with the GSTP1 rs1695 AA genotype carriers, patients with AG and GG genotypes had an increased risk of cyclophosphamide-induced gastrointestinal toxicity (RR, 1.61; 95% CI, 1.18-2.19; P = .003) and infection (RR, 1.57; 95% CI, 1.00-2.48; P = .05) in the overall population. In the subgroup analyses, there were significant associations between GSTP1 rs1695 polymorphism and the risk of cyclophosphamide-induced myelosuppression (RR, 2.10; 95% CI, 1.60-2.76; P < .00001), gastrointestinal toxicity (RR, 1.77; 95%CI, 1.25-2.53; P = .001), and infection (RR, 2.01; 95% CI, 1.14-3.54; P = .02) in systemic lupus erythematosus (SLE) or lupus nephritis syndrome patients, but not in cancer patients.Our results confirmed an essential role for the GSTP1 rs1695 polymorphism in the prediction of cyclophosphamide-induced myelosuppression, gastrointestinal toxicity, and infection in SLE or lupus nephritis syndrome patients. More studies are necessary to validate our findings in the future.


Assuntos
Ciclofosfamida/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/genética , Predisposição Genética para Doença/genética , Glutationa S-Transferase pi/genética , Polimorfismo Genético , Gastroenteropatias/induzido quimicamente , Gastroenteropatias/genética , Genótipo , Humanos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Nefrite Lúpica/tratamento farmacológico , Estudos Observacionais como Assunto , Fatores de Risco
9.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(1): 55-60, 2021 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-33476538

RESUMO

OBJECTIVE: To study the clinicopathological features of children with lupus nephritis (LN) with positive anti-neutrophil cytoplasmic antibody (ANCA). METHODS: A retrospective analysis was performed for the children who were diagnosed with LN in the First Affiliated Hospital of Sun Yat-sen University from January 2003 to December 2019. According to the results of serum ANCA, they were divided into two groups: ANCA-positive group (n=59) and ANCAnegative group (n=454). The two groups were compared in terms of clinical manifestations, histopathological features, remission rate, and prognosis. RESULTS: Compared with the ANCA-negative group, the ANCA-positive group had a significant reduction in leukocytes and a significant increase in erythrocyte sedimentation rate (P < 0.05). There were no significant differences between the two groups in serum creatinine, urine protein, and urine red blood cell count (P > 0.05). A total of 308 children underwent kidney biopsy. The results on light microscopy showed that compared with the ANCAnegative group, the ANCA-positive group had a significantly higher proportion of children with cellular fibrous crescents (P < 0.05) and a significantly lower proportion of children with immune complex deposition (P < 0.05). There were no significant differences between the two groups in the remission rate and survival rate (P > 0.05). CONCLUSIONS: Children with ANCA-positive LN tend to have more severe renal pathological injury, which is not exactly parallel with clinical manifestations, suggesting that timely renal biopsy is of great importance.


Assuntos
Anticorpos Anticitoplasma de Neutrófilos , Nefrite Lúpica , Criança , Creatinina , Humanos , Rim , Estudos Retrospectivos
10.
Methods Mol Biol ; 2225: 241-255, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33108667

RESUMO

Systemic lupus erythematosus (SLE) is a multifactorial and heterogeneous autoimmune disease involving multiple organ systems and tissues. Lupus nephritis occurs in approximately 60% of patients with SLE and is the leading cause of morbidity. Diffuse alveolar hemorrhage (DAH) is a rare but very serious complication of SLE with a greater than 50% associated mortality. The etiology of SLE is unclear but has proposed genetic, hormonal, and environmental aspects. Pristane is a saturated terpenoid alkane and has become the most popular laboratory model for inducing lupus in mice. The pristane model of SLE has the capacity to reproduce many components of the human presentation of the disease. Previous studies have demonstrated that virus-derived immune-modulating proteins have the potential to control inflammatory and autoimmune disorders. Serp-1, a 55 kDa secreted and highly glycosylated immune modulator derived from myxoma virus (MYXV), has potent immunomodulatory activity in models of vasculitis, viral sepsis, collagen-induced arthritis, and transplant rejection. This chapter describes the mouse preclinical pristane lupus model as a method to examine virus-derived protein efficacy for treating autoimmune diseases and specifically lupus nephritis and DAH.


Assuntos
Avaliação Pré-Clínica de Medicamentos/métodos , Hemorragia/prevenção & controle , Fatores Imunológicos/farmacologia , Nefrite Lúpica/tratamento farmacológico , Myxoma virus/química , Proteinúria/tratamento farmacológico , Proteínas Virais/farmacologia , Animais , Autoanticorpos/biossíntese , Citocinas/biossíntese , Modelos Animais de Doenças , Feminino , Hemorragia/imunologia , Hemorragia/patologia , Humanos , Fatores Imunológicos/imunologia , Injeções Intraperitoneais , Pulmão/irrigação sanguínea , Pulmão/efeitos dos fármacos , Pulmão/patologia , Nefrite Lúpica/induzido quimicamente , Nefrite Lúpica/imunologia , Nefrite Lúpica/patologia , Camundongos , Camundongos Endogâmicos BALB C , Proteinúria/induzido quimicamente , Proteinúria/imunologia , Proteinúria/patologia , Terpenos/administração & dosagem , Resultado do Tratamento , Proteínas Virais/imunologia
11.
Am J Med Sci ; 361(3): 336-343, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33309135

RESUMO

BACKGROUND: This study aimed to explore the associations between the complement factor H (CFH) rs6677604 and clinico-pathological characteristics of lupus nephritis. MATERIALS AND METHODS: A total of 188 patients with lupus nephritis with complete clinico-pathological data were enrolled and genotyping of CFH rs6677604 was conducted by TaqMan SNP genotyping assays. Patients were divided into two groups by rs6677604-AA/AG or -GG, and the clinico-pathological features between the two groups were further compared. RESULTS: We found that patients with rs6677604-AA/AG presented with lower prevalence of anti-dsDNA antibody (12/24 [50.0%] vs 121/164 [73.8%], P = 0.028), higher level of plasma C3a (2642.96 ± 1575.05 vs 1640.01 ± 1209.40, ng/ml, P = 0.024), and a tendency for higher level of plasma CFH (505.76 ± 169.28 vs 397.67 ± 179.11, µg/ml, P = 0.087). Patients with rs6677604-AA/AG had milder renal histopathological features, including total activity indices score (4.5[0, 13] vs 8[0, 19], P = 0.013), endocapillary hypercellularity (1.5[0, 3] vs 3[0, 3], P = 0.013), sub-endothelial hyaline deposits (0.5[0, 3] vs 1[0,3], P = 0.021), glomerular leukocyte infiltration (0.5[0, 1] vs 1[0, 12], P = 0.023) and tubular atrophy (1[0, 1] vs 1[0, 3], P = 0.027) than those with rs6677604-GG, which was further confirmed by the stratified analysis. The rs6677604-A was not a risk factor for patients' renal outcomes (hazard ratio=0.898; 95% CI: 0.264-3.059, P = 0.863). CONCLUSIONS: The rs6677604-A genotype in CFH was associated with milder renal pathological features in lupus nephritis, and its protective effect on the pathogenesis of the disease remained to be elucidated.


Assuntos
Nefrite Lúpica/genética , Adolescente , Adulto , Idoso , Fator H do Complemento/genética , Fator H do Complemento/metabolismo , Feminino , Variação Genética , Genótipo , Humanos , Nefrite Lúpica/fisiopatologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
13.
Blood ; 136(25): 2933-2945, 2020 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-33331924

RESUMO

Systemic lupus erythematosus (SLE) is an autoimmune inflammatory disease characterized by deposits of immune complexes (ICs) in organs and tissues. The expression of FcγRIIA by human platelets, which is their unique receptor for immunoglobulin G antibodies, positions them to ideally respond to circulating ICs. Whereas chronic platelet activation and thrombosis are well-recognized features of human SLE, the exact mechanisms underlying platelet activation in SLE remain unknown. Here, we evaluated the involvement of FcγRIIA in the course of SLE and platelet activation. In patients with SLE, levels of ICs are associated with platelet activation. Because FcγRIIA is absent in mice, and murine platelets do not respond to ICs in any existing mouse model of SLE, we introduced the FcγRIIA (FCGR2A) transgene into the NZB/NZWF1 mouse model of SLE. In mice, FcγRIIA expression by bone marrow cells severely aggravated lupus nephritis and accelerated death. Lupus onset initiated major changes to the platelet transcriptome, both in FcγRIIA-expressing and nonexpressing mice, but enrichment for type I interferon response gene changes was specifically observed in the FcγRIIA mice. Moreover, circulating platelets were degranulated and were found to interact with neutrophils in FcγRIIA-expressing lupus mice. FcγRIIA expression in lupus mice also led to thrombosis in lungs and kidneys. The model recapitulates hallmarks of human SLE and can be used to identify contributions of different cellular lineages in the manifestations of SLE. The study further reveals a role for FcγRIIA in nephritis and in platelet activation in SLE.


Assuntos
Autoanticorpos/imunologia , Plaquetas/imunologia , Imunoglobulina G/imunologia , Nefrite Lúpica/imunologia , Ativação Plaquetária/imunologia , Receptores de IgG/imunologia , Animais , Autoanticorpos/genética , Plaquetas/patologia , Modelos Animais de Doenças , Imunoglobulina G/genética , Nefrite Lúpica/genética , Nefrite Lúpica/patologia , Camundongos , Camundongos Transgênicos , Ativação Plaquetária/genética , Receptores de IgG/genética
14.
Front Immunol ; 11: 599417, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33362783

RESUMO

The complement system comprises the frontline of the innate immune system. Triggered by pathogenic surface patterns in different pathways, the cascade concludes with the formation of a membrane attack complex (MAC; complement components C5b to C9) and C5a, a potent anaphylatoxin that elicits various inflammatory signals through binding to C5a receptor 1 (C5aR1). Despite its important role in pathogen elimination, priming and recruitment of myeloid cells from the immune system, as well as crosstalk with other physiological systems, inadvertent activation of the complement system can result in self-attack and overreaction in autoinflammatory diseases. Consequently, it constitutes an interesting target for specialized therapies. The paradigm of safe and efficacious terminal complement pathway inhibition has been demonstrated by the approval of eculizumab in paroxysmal nocturnal hematuria. In addition, complement contribution in rare kidney diseases, such as lupus nephritis, IgA nephropathy, atypical hemolytic uremic syndrome, C3 glomerulopathy, or antineutrophil cytoplasmic antibody-associated vasculitis has been demonstrated. This review summarizes the involvement of the terminal effector agents of the complement system in these diseases and provides an overview of inhibitors for complement components C5, C5a, C5aR1, and MAC that are currently in clinical development. Furthermore, a link between increased complement activity and lung damage in severe COVID-19 patients is discussed and the potential for use of complement inhibitors in COVID-19 is presented.


Assuntos
Complemento C5a/antagonistas & inibidores , Inativadores do Complemento/uso terapêutico , Complexo de Ataque à Membrana do Sistema Complemento/antagonistas & inibidores , Nefropatias/tratamento farmacológico , Receptor da Anafilatoxina C5a/antagonistas & inibidores , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/patologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Ativação do Complemento/imunologia , Proteínas do Sistema Complemento/metabolismo , Glomerulonefrite por IGA/tratamento farmacológico , Glomerulonefrite por IGA/patologia , Humanos , Rim/patologia , Nefropatias/imunologia , Nefropatias/patologia , Nefrite Lúpica/tratamento farmacológico , Nefrite Lúpica/patologia
15.
Yonsei Med J ; 61(11): 951-957, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33107238

RESUMO

PURPOSE: To compare the clinical characteristics and renal outcomes between patients who initially had lupus nephritis (LN) at the onset of systemic lupus erythematosus (SLE) (initial-onset LN) and those who developed LN within 5 years after SLE onset (early-onset LN). MATERIALS AND METHODS: SLE patients with biopsy-proven LN were retrospectively reviewed. The clinical parameters and renal outcomes were compared between initial-onset and early-onset LN groups. We used Cox regression analysis to estimate risk of worse renal outcomes according to the onset time of LN. RESULTS: Of all 136 LN patients, 92 (67.6%) and 44 (32.4%) patients were classified into the initial-onset and early-onset LN groups, respectively. The initial-onset LN group had higher prevalences of class IV LN (54.3% vs. 34.1%, p=0.027), impaired renal function (34.8% vs. 11.4%, p=0.004), microscopic hematuria (73.9% vs. 54.5%, p=0.024), and higher urine protein/creatinine ratio [4626.1 (2180.0-6788.3) mg/g vs. 2410.0 (1265.0-5168.5) mg/g, p=0.006] at LN diagnosis. Renal relapse (46.3% vs. 25.7%, p=0.039) and progression to chronic kidney disease (CKD) or end-stage renal disease (ESRD) were more common (24.4% vs. 8.3%, p=0.042) in the initial-onset LN group. In Cox regression analysis, the initial-onset LN group had higher risks of renal relapse [adjusted hazard ratio (HR) 3.56, 95% confidence interval (CI) 1.51-8.35, p=0.004] and progression to CKD or ESRD (adjusted HR 4.57, 95% CI 1.03-20.17, p=0.045), compared with the early-onset LN group. CONCLUSION: Patients with LN at SLE onset may have more severe renal presentations and experience worse renal outcomes than those who develop LN within 5 years.


Assuntos
Falência Renal Crônica/etiologia , Rim/fisiopatologia , Lúpus Eritematoso Sistêmico/patologia , Nefrite Lúpica/patologia , Adulto , Biópsia , Progressão da Doença , Feminino , Humanos , Lúpus Eritematoso Sistêmico/terapia , Nefrite Lúpica/complicações , Nefrite Lúpica/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores de Tempo , Adulto Jovem
16.
Pediatrics ; 146(5)2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33122347

RESUMO

Hemophilia A (HA) is a serious inherited bleeding disorder resulting from a deficiency of coagulation factor VIII (FVIII). Replacement therapy with intravenous infusion of FVIII can be associated with treatment failure in approximately one-third of patients secondary to the development of neutralizing alloantibodies (inhibitor). Emicizumab is a recombinant, humanized, bispecific monoclonal antibody that binds factor IXa and factor X and mimics FVIII. It has been licensed in many countries for the treatment of patients with HA with and without inhibitors with a favorable efficacy and safety profile. A 7-year-old child with severe HA and FVIII inhibitors, refractory to immune tolerance therapy, developed hematuria with nephrotic-range proteinuria after the first dose of emicizumab and subsequently also after a second dose 6 weeks later, which was associated with mild and transient leukopenia. Renal biopsy revealed a pattern of a full-house lupus nephritis. The patient fully and spontaneously recovered between 2 weeks after symptoms onset. In this report, we provide insights on a new and so far unreported renal complication associated to emicizumab treatment. Although emicizumab offers significant benefits for patient with HA, clinicians should be aware of this rare and potential serious renal adverse effect.


Assuntos
Anticorpos Biespecíficos/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Hemofilia A/terapia , Nefrite Lúpica/etiologia , Criança , Fator VIII/imunologia , Hemofilia A/sangue , Humanos , Leucopenia/etiologia , Nefrite Lúpica/sangue , Nefrite Lúpica/imunologia , Nefrite Lúpica/patologia , Masculino
17.
Medicine (Baltimore) ; 99(38): e22328, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32957400

RESUMO

BACKGROUND: Lupus nephritis (LN) remains a predominant cause of morbidity and mortality in SLE. Here we performed a meta-analysis to evaluate the efficacy and safety of the induction treatment with mycophenolate mofetil (MMF) and cyclophosphamide (CYC) for LN. METHODS: Relevant literature was searched by computer from the establishment of the database to November 2019. A meta-analysis was conducted to analysis the efficacy and safety between mycophenolate mofetil and cyclophosphamide as induction therapy in LN patients. The primary end-point was response to urine protein, serum creatinine (Scr) and serum complement C3, and the secondary end-points were complete remission and adverse reactions. RESULTS: Eighteen articles were selected for the final meta-analysis, involving 1989 patients with LN, of which the renal biopsy result could be classified into class III-V according to the standards of WHO/ISN. The results revealed that MMF was superior to CYC in increasing the level of serum complement C3 [SMD = 0.475, 95%CI (0.230-0.719)] and complete remission [RR = 1.231, 95%CI (1.055-1.437)]. Furthermore, the subgroup analysis showed that it was in Asian patients, rather than in Caucasian patients, that CYC exerted a better effect on lowering the level of urine protein (UPRO) than MMF [SMD = 0.405, 95%CI (0.081-0.730)]. Besides, when the initial UPRO level was less than 4 g/day, the effect of CYC was better than MMF [SMD = 0.303, 95%CI (0.014-0.591)]. There was no significant difference between MMF and CYC in improving Scr [SMD = 0.090, 95%CI (-0.060-0.239)]. When it came to the comparison of safety between MMF and CYC, the meta-analysis showed that MMF was superior to CYC in decreasing infection in Caucasian patients [RR = 0.727, 95%CI (0.532-0.993)], reducing the risk of leukopenia and menstrual abnormalities in Asian patients and lowering the frequency of gastrointestinal symptoms [RR = 0.639, 95%CI (0.564-0.724)], independent of race. CONCLUSIONS: MMF precedes CYC in improving serum complement C3 and complete remission regardless of race, as well as shows fewer adverse drug reactions in the induction treatment of LN belonging to type III-V. But for Asian patients or those initial UPRO levels are less than 4 g/day, CYC may be superior to MMF.


Assuntos
Ciclofosfamida/uso terapêutico , Nefrite Lúpica/tratamento farmacológico , Ácido Micofenólico/uso terapêutico , Adulto , Feminino , Humanos , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , Indução de Remissão
18.
N Engl J Med ; 383(12): 1117-1128, 2020 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-32937045

RESUMO

BACKGROUND: In adults with active lupus nephritis, the efficacy and safety of intravenous belimumab as compared with placebo, when added to standard therapy (mycophenolate mofetil or cyclophosphamide-azathioprine), are unknown. METHODS: In a phase 3, multinational, multicenter, randomized, double-blind, placebo-controlled, 104-week trial conducted at 107 sites in 21 countries, we assigned adults with biopsy-proven, active lupus nephritis in a 1:1 ratio to receive intravenous belimumab (at a dose of 10 mg per kilogram of body weight) or matching placebo, in addition to standard therapy. The primary end point at week 104 was a primary efficacy renal response (a ratio of urinary protein to creatinine of ≤0.7, an estimated glomerular filtration rate [eGFR] that was no worse than 20% below the value before the renal flare (pre-flare value) or ≥60 ml per minute per 1.73 m2 of body-surface area, and no use of rescue therapy), and the major secondary end point was a complete renal response (a ratio of urinary protein to creatinine of <0.5, an eGFR that was no worse than 10% below the pre-flare value or ≥90 ml per minute per 1.73 m2, and no use of rescue therapy). The time to a renal-related event or death was assessed. RESULTS: A total of 448 patients underwent randomization (224 to the belimumab group and 224 to the placebo group). At week 104, significantly more patients in the belimumab group than in the placebo group had a primary efficacy renal response (43% vs. 32%; odds ratio, 1.6; 95% confidence interval [CI], 1.0 to 2.3; P = 0.03) and a complete renal response (30% vs. 20%; odds ratio, 1.7; 95% CI, 1.1 to 2.7; P = 0.02). The risk of a renal-related event or death was lower among patients who received belimumab than among those who received placebo (hazard ratio, 0.51; 95% CI, 0.34 to 0.77; P = 0.001). The safety profile of belimumab was consistent with that in previous trials. CONCLUSIONS: In this trial involving patients with active lupus nephritis, more patients who received belimumab plus standard therapy had a primary efficacy renal response than those who received standard therapy alone. (Funded by GlaxoSmithKline; BLISS-LN ClinicalTrials.gov number, NCT01639339.).


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Imunossupressores/uso terapêutico , Nefrite Lúpica/tratamento farmacológico , Adulto , Anticorpos Monoclonais Humanizados/efeitos adversos , Azatioprina/uso terapêutico , Creatinina/urina , Ciclofosfamida/uso terapêutico , Método Duplo-Cego , Quimioterapia Combinada , Inibidores Enzimáticos/uso terapêutico , Feminino , Taxa de Filtração Glomerular , Humanos , Imunossupressores/efeitos adversos , Infusões Intravenosas , Análise de Intenção de Tratamento , Nefrite Lúpica/mortalidade , Masculino , Ácido Micofenólico/uso terapêutico , Indução de Remissão
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