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1.
Ann Rheum Dis ; 79(6): 713-723, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32220834

RESUMO

OBJECTIVE: To update the 2012 EULAR/ERA-EDTA recommendations for the management of lupus nephritis (LN). METHODS: Following the EULAR standardised operating procedures, a systematic literature review was performed. Members of a multidisciplinary Task Force voted independently on their level of agreeement with the formed statements. RESULTS: The changes include recommendations for treatment targets, use of glucocorticoids and calcineurin inhibitors (CNIs) and management of end-stage kidney disease (ESKD). The target of therapy is complete response (proteinuria <0.5-0.7 g/24 hours with (near-)normal glomerular filtration rate) by 12 months, but this can be extended in patients with baseline nephrotic-range proteinuria. Hydroxychloroquine is recommended with regular ophthalmological monitoring. In active proliferative LN, initial (induction) treatment with mycophenolate mofetil (MMF 2-3 g/day or mycophenolic acid (MPA) at equivalent dose) or low-dose intravenous cyclophosphamide (CY; 500 mg × 6 biweekly doses), both combined with glucocorticoids (pulses of intravenous methylprednisolone, then oral prednisone 0.3-0.5 mg/kg/day) is recommended. MMF/CNI (especially tacrolimus) combination and high-dose CY are alternatives, for patients with nephrotic-range proteinuria and adverse prognostic factors. Subsequent long-term maintenance treatment with MMF or azathioprine should follow, with no or low-dose (<7.5 mg/day) glucocorticoids. The choice of agent depends on the initial regimen and plans for pregnancy. In non-responding disease, switch of induction regimens or rituximab are recommended. In pure membranous LN with nephrotic-range proteinuria or proteinuria >1 g/24 hours despite renin-angiotensin-aldosterone blockade, MMF in combination with glucocorticoids is preferred. Assessment for kidney and extra-renal disease activity, and management of comorbidities is lifelong with repeat kidney biopsy in cases of incomplete response or nephritic flares. In ESKD, transplantation is the preferred kidney replacement option with immunosuppression guided by transplant protocols and/or extra-renal manifestations. Treatment of LN in children follows the same principles as adult disease. CONCLUSIONS: We have updated the EULAR recommendations for the management of LN to facilitate homogenization of patient care.


Assuntos
Imunossupressores/uso terapêutico , Nefrite Lúpica/tratamento farmacológico , Sociedades Médicas , Antirreumáticos/uso terapêutico , Azatioprina/uso terapêutico , Inibidores de Calcineurina/uso terapêutico , Quimioterapia Combinada , Europa (Continente) , Taxa de Filtração Glomerular , Glucocorticoides/uso terapêutico , Humanos , Hidroxicloroquina/uso terapêutico , Falência Renal Crônica/etiologia , Falência Renal Crônica/terapia , Nefrite Lúpica/complicações , Nefrite Lúpica/patologia , Nefrite Lúpica/fisiopatologia , Ácido Micofenólico/uso terapêutico , Proteinúria/etiologia , Proteinúria/terapia
2.
Am J Kidney Dis ; 76(2): 265-281, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32220510

RESUMO

Systemic lupus erythematosus is a multisystem autoimmune disease that commonly affects the kidneys. Lupus nephritis (LN) is the most common cause of kidney injury in systemic lupus erythematosus and a major risk factor for morbidity and mortality. The pathophysiology of LN is heterogeneous. Genetic and environmental factors likely contribute to this heterogeneity. Despite improved understanding of the pathogenesis of LN, treatment advances have been few and risk for kidney failure remains unacceptably high. This installment in the Core Curriculum of Nephrology provides an up-to-date review of the current understanding of LN epidemiology, pathogenesis, diagnosis, and treatment. Challenging issues such as the management of LN in pregnancy, timing of transplantation, and the evolving role of corticosteroid use in the management of LN are discussed. We review the currently accepted approach to care for patients with LN and highlight deficiencies that need to be addressed to better preserve long-term kidney health and improve outcomes in LN.


Assuntos
Corticosteroides/uso terapêutico , Fatores Imunológicos/uso terapêutico , Falência Renal Crônica/terapia , Transplante de Rim , Nefrite Lúpica , Diálise Renal , Imunidade Adaptativa/imunologia , Distribuição por Idade , Autoanticorpos/imunologia , Autoimunidade/imunologia , Biópsia , Ciclofosfamida/uso terapêutico , Feminino , Humanos , Hidroxicloroquina/uso terapêutico , Imunidade Inata/imunologia , Imunossupressores/uso terapêutico , Quimioterapia de Indução , Falência Renal Crônica/etiologia , Nefrite Lúpica/tratamento farmacológico , Nefrite Lúpica/epidemiologia , Nefrite Lúpica/patologia , Nefrite Lúpica/fisiopatologia , Quimioterapia de Manutenção , Masculino , Ácido Micofenólico/uso terapêutico , Gravidez , Complicações na Gravidez , Urinálise
3.
Arthritis Rheumatol ; 72(7): 1134-1142, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32017464

RESUMO

OBJECTIVE: To identify potential clusters of systemic lupus erythematosus (SLE) organ-specific flares and their relationship to fine particulate matter pollution (PM2.5), temperature, ozone concentration, resultant wind, relative humidity, and barometric pressure in the Hopkins Lupus Cohort, using spatiotemporal cluster analysis. METHODS: A total of 1,628 patients who fulfilled the Systemic Lupus International Collaborating Clinics classification criteria for SLE and who had a home address recorded were included in the analysis. Disease activity was assessed using the Lupus Activity Index. Assessment of rash, joint involvement, serositis, and neurologic, pulmonary, renal, and hematologic activity was quantified on a 0-3 visual analog scale (VAS). An organ-specific flare was defined as an increase in VAS of ≥1 point compared to the previous visit. Spatiotemporal clusters were detected using SaTScan software. Regression models were used for cluster adjustment and included individual, county-level, and environmental variables. RESULTS: Significant clusters unadjusted for environmental variables were identified for joint flares (P < 0.05; n = 3), rash flares (P < 0.05; n = 4), hematologic flares (P < 0.05; n = 3), neurologic flares (P < 0.05; n = 2), renal flares (P < 0.001; n = 4), serositis (P < 0.001; n = 2), and pulmonary flares (P < 0.001; n = 2). The majority of the clusters identified changed in significance, temporal extent, or spatial extent after adjustment for environmental variables. CONCLUSION: We describe the first spatiotemporal clusters of lupus organ-specific flares. Seasonal, as well as multi-year, cluster patterns were identified, differing in extent and location for the various organ-specific flare types. Further studies focusing on each individual organ-specific flare are needed to better understand the driving forces behind these observed changes.


Assuntos
Poluição do Ar/estatística & dados numéricos , Pressão Atmosférica , Lúpus Eritematoso Sistêmico/fisiopatologia , Material Particulado , Exacerbação dos Sintomas , Tempo (Meteorologia) , Adulto , Artrite/fisiopatologia , Estudos de Coortes , Exantema/fisiopatologia , Feminino , Doenças Hematológicas/fisiopatologia , Humanos , Umidade , Pneumopatias/fisiopatologia , Nefrite Lúpica/fisiopatologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/fisiopatologia , Masculino , Ozônio , Serosite/fisiopatologia , Análise Espaço-Temporal , Temperatura , Vento
4.
Lupus ; 29(1): 52-57, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31793379

RESUMO

BACKGROUND: Reduced renal function is associated with worse renal outcome in patients with lupus nephritis (LN). However, there is insufficient knowledge regarding renal function recovery in patients with LN with reduced baseline renal function. Therefore, the present study aimed to investigate renal function recovery and related factors in patients with reduced baseline renal function. METHODS: The present retrospective longitudinal cohort study included patients with LN and reduced renal function. Reduced renal function was defined as an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m2. Recovery of renal function was determined by an eGFR of >60 mL/min/1.73 m2 at six months after baseline, and factors associated with it were evaluated using logistic regression analysis. RESULTS: We included 90 patients with LN, with a mean eGFR value of 37.2 ± 13.9 mL/min/1.73 m2. Forty-six (51.1%) patients recovered their renal function after six months. On multivariate analysis, hydroxychloroquine use (odds ratio (OR) = 3.891, 95% confidence interval (CI) 1.196-12.653, p = 0.024), prolonged LN (OR = 0.926, 95% CI 0.874-0.981, p = 0.009) and high-grade tubular atrophy (OR = 0.451, 95% CI 0.208-0.829, p = 0.013) were associated with renal function recovery. During follow up, 25 patients were on end-stage renal disease (ESRD). Kaplan-Meier analysis revealed that renal function recovery after six months and lower probability of ESRD are associated. CONCLUSIONS: In patients with LN and reduced renal function, renal function recovery at six months was associated with use of hydroxychloroquine and inversely related to longer duration of LN and higher grade of tubular atrophy.


Assuntos
Antirreumáticos/uso terapêutico , Taxa de Filtração Glomerular/efeitos dos fármacos , Hidroxicloroquina/uso terapêutico , Nefrite Lúpica/tratamento farmacológico , Adulto , Antirreumáticos/farmacologia , Feminino , Humanos , Hidroxicloroquina/farmacologia , Estudos Longitudinais , Nefrite Lúpica/fisiopatologia , Masculino , Pessoa de Meia-Idade , Recuperação de Função Fisiológica/efeitos dos fármacos , Estudos Retrospectivos
5.
Lupus ; 29(1): 83-91, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31801041

RESUMO

OBJECTIVE: We analyzed baseline and follow-up characteristics related to poorer renal outcomes in a Brazilian cohort of admixture race patients with lupus nephritis. METHODS: Overall, 280 outpatients with a diagnosis of systemic lupus erythematosus and previous kidney biopsy of lupus nephritis were recruited from August 2015 to December 2018 and had baseline laboratory and histologic data retrospectively analyzed; patients were then followed-up and data were recorded. The main outcome measure was the estimated glomerular filtration rate at last follow-up. Secondary analyses assessed the impact of initial kidney histology and treatment in long-term kidney survival. RESULTS: Median duration of lupus nephritis was 60 months (interquartile range: 27-120); 40 (14.3%) patients presented progressive chronic kidney disease (estimated glomerular filtration rate <30 and ≥10 ml/min/1.73 m2) or end-stage kidney disease at last visit. Adjusted logistic regression analysis showed that class IV lupus nephritis (odds ratio 14.91; 95% confidence interval 1.77-125.99; p = 0.01) and interstitial fibrosis ≥25% at initial biopsy (odds ratio 5.87; 95% confidence interval 1.32-26.16; p = 0.02), lack of complete or partial response at 12 months (odds ratio 16.3; 95% confidence interval 3.74-71.43; p < 0.001), and a second renal flare (odds ratio 4.49; 95% confidence interval 1.10-18.44; p = 0.04) were predictors of progressive chronic kidney disease. In a Kaplan-Meier survival curve we found that class IV lupus nephritis and interstitial fibrosis ≥25% were significantly associated with end-stage kidney disease throughout follow-up (hazard ratio 2.96; 95% confidence interval 1.3-7.0; p = 0.036 and hazard ratio 4.96; 95% confidence interval 1.9-12.9; p < 0.0001, respectively). CONCLUSION: In this large cohort of admixture race patients, class IV lupus nephritis and chronic interstitial damage at initial renal biopsy together with non-response after 1 year of therapy and relapse were associated with worse long-term renal outcomes.


Assuntos
Progressão da Doença , Falência Renal Crônica/etiologia , Nefrite Lúpica/fisiopatologia , Adulto , Brasil , Estudos de Coortes , Feminino , Taxa de Filtração Glomerular , Humanos , Nefrite Lúpica/classificação , Nefrite Lúpica/complicações , Masculino , Pessoa de Meia-Idade
6.
Iran J Kidney Dis ; 13(6): 389-397, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31880585

RESUMO

INTRODUCTION: Kidney involvement is a hallmark of systemic lupus erythematosus (SLE) and evaluation of its inflammatory response is demanding. It was the aim of the present study to evaluate the levels of CXCL10 and vitamin D in serum samples of cases with active lupus nephritis (LN). METHODS: Fifty lupus patients were enrolled in our study, 25 patients had lupus nephritis and 25 patients were without evidence of LN. Thirty-nine healthy subjects were also participated as a control group. Complete biochemical and serological parameters were measured and their correlation with serum levels of vitamin D and CXCL10 were assessed in the studied groups. RESULTS: Serum levels of CXCL10 were significantly elevated (P≤ 0.020), while vitamin D were diminished in SLE group and active LN as compared with healthy controls and SLE patients without nephritis, respectively. CXCL10 correlated with SLE disease activity index (SLEDAI) and renal activity (P < .05), while vitamin D correlated with C3 and anti-dsDNA antibody (P < .05). Based on the receiver operator characteristic (ROC) curve analysis, CXCL10 and vitamin D levels were not better than conventional biomarkers for discriminating LN patients from non-nephritis SLE patients; however, they could differentiate most of SLE cases from healthy individuals with area under the curve (AUC) ≥ 0.703 (P < .05). CONCLUSION: Results indicated the importance of elevated levels of CXCL10 and deficiency of vitamin D on the pathogenesis of active LN disease.


Assuntos
Quimiocina CXCL10/sangue , Nefrite Lúpica/sangue , Deficiência de Vitamina D/sangue , Vitamina D/sangue , Adulto , Biomarcadores/sangue , Feminino , Humanos , Testes de Função Renal , Lúpus Eritematoso Sistêmico/diagnóstico , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/fisiopatologia , Masculino , Pessoa de Meia-Idade , Curva ROC , Índice de Gravidade de Doença
8.
Adv Chronic Kidney Dis ; 26(5): 313-322, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31733715

RESUMO

Lupus nephritis (LN) is the cause of end-stage kidney disease (ESKD) for 1.9% of the ESKD population in the United States. Although the incidence rates of ESKD from LN stopped rising in recent years, racial disparities in waiting time, pre-emptive kidney transplant, and transplant outcomes still exist. Patients with LN who progress to ESKD tend to be female, of African ancestry, and young. Kidney transplantation is safe in this population and associated with a substantial survival benefit, primarily due to reduced deaths from cardiovascular disease and infection. Transplant outcomes for patients with ESKD due to LN are similar to those without LN.


Assuntos
Falência Renal Crônica/cirurgia , Transplante de Rim , Nefrite Lúpica , Humanos , Falência Renal Crônica/etiologia , Transplante de Rim/efeitos adversos , Transplante de Rim/métodos , Nefrite Lúpica/epidemiologia , Nefrite Lúpica/imunologia , Nefrite Lúpica/fisiopatologia , Nefrite Lúpica/terapia , Recidiva , Fatores de Risco , Análise de Sobrevida , Resultado do Tratamento
9.
Adv Chronic Kidney Dis ; 26(5): 330-337, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31733717

RESUMO

Pregnancy is an altered immunologic state in which hormonal changes impact the immune system to enable maternal tolerance of the fetus. These hormonal and immunologic changes may affect disease activity in systemic lupus erythematosus. Conversely, lupus nephritis and its complications may adversely impact pregnancy. Systemic lupus erythematosus increases the risk of pre-eclampsia and its complications, including preterm birth and intrauterine growth restriction. Comorbidities such as impaired kidney function and hypertension confer additional risk and complexity. Medications used to treat lupus nephritis may impact the fetus, so therapy needs to be tailored to balance maternal benefit and fetal risk. The diagnosis of lupus nephritis during pregnancy can be difficult, as it shares overlapping features with pre-eclampsia. Kidney biopsy is generally safe in pregnancy, and should be considered if the result will affect management. Here we review the clinical aspects of counseling, diagnosis, and management of lupus nephritis in pregnancy.


Assuntos
Nefrite Lúpica , Complicações na Gravidez , Cuidado Pré-Natal/métodos , Feminino , Humanos , Recém-Nascido , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/imunologia , Nefrite Lúpica/fisiopatologia , Nefrite Lúpica/terapia , Gravidez , Complicações na Gravidez/diagnóstico , Complicações na Gravidez/imunologia , Complicações na Gravidez/fisiopatologia , Complicações na Gravidez/terapia , Risco Ajustado , Medição de Risco
10.
Adv Chronic Kidney Dis ; 26(5): 338-350, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31733718

RESUMO

The majority of patients with systemic lupus erythematosus develop lupus nephritis (LN) which significantly contributes to increased risks of hospitalizations, ESRD, and death. Unfortunately, treatments for LN have not changed over the past 15 years. Despite continued efforts to elucidate the pathogenesis of LN, no new drugs have yet replaced the standard-of-care regimens of cyclophosphamide or mycophenolate mofetil plus high-dose corticosteroids. The significant limitations of standard-of-care are low complete response rates, risk of flares, and ongoing inflammation in the kidney leading to progressive renal dysfunction. Repeat and prolonged treatments are often needed to control disease, leading to a high level of severe side effects. The development of targeted drugs with better efficacy and safety are desperately needed. The rationale for targeting key immunologic pathways in LN continues to be strongly supported by basic and translational research and has generated the hope and excitement of testing these therapies in human LN. This review provides an overview of biologics studied to date in clinical trials of LN, discusses the potential reasons for their failure, and addresses the challenges moving forward.


Assuntos
Produtos Biológicos , Nefrite Lúpica , Produtos Biológicos/imunologia , Produtos Biológicos/farmacologia , Ensaios Clínicos como Assunto , Humanos , Nefrite Lúpica/imunologia , Nefrite Lúpica/fisiopatologia , Nefrite Lúpica/terapia , Conduta do Tratamento Medicamentoso , Terapias em Estudo/métodos , Resultado do Tratamento
11.
Adv Chronic Kidney Dis ; 26(5): 369-375, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31733721

RESUMO

In systemic lupus erythematosus, nephrotic-range proteinuria typically signals the presence of a proliferative lupus nephritis (class III/IV) and/or membranous lupus nephritis (class V, with or without concomitant class III or IV lesions). However, in rare instances, systemic lupus erythematosus patients with nephrotic syndrome have kidney biopsy findings of normal glomeruli or focal segmental glomerulosclerosis lesions, with or without mesangial proliferation, on light microscopy; the absence of subepithelial or subendothelial deposits on immunofluorescence and electron microscopy; and diffuse foot process effacement on electron microscopy. This pattern, termed lupus podocytopathy, is a unique form of lupus nephritis that mimics minimal change disease or primary focal segmental glomerulosclerosis and represents approximately 1% of lupus nephritis biopsies. Here we review the clinical features, histological manifestations, diagnostic criteria and classification, pathogenesis, treatment, and prognosis of lupus podocytopathy.


Assuntos
Glomérulos Renais , Lúpus Eritematoso Sistêmico/complicações , Nefrite Lúpica , Podócitos/patologia , Gerenciamento Clínico , Humanos , Glomérulos Renais/diagnóstico por imagem , Glomérulos Renais/patologia , Nefrite Lúpica/etiologia , Nefrite Lúpica/patologia , Nefrite Lúpica/fisiopatologia , Nefrite Lúpica/terapia , Síndrome Nefrótica/diagnóstico , Síndrome Nefrótica/etiologia
12.
Adv Chronic Kidney Dis ; 26(5): 393-403, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31733724

RESUMO

Membranous lupus nephritis (MLN) (Class V lupus nephritis [LN]) is a distinct form of LN defined by the presence of subepithelial immune complex deposits seen on kidney biopsy. MLN is often associated with the nephrotic syndrome. The histology of MLN closely resembles that of idiopathic (primary) membranous nephropathy (pMN). However, MLN typically has abundant mesangial deposits that are absent in primary membranous nephropathy. The clinical presentation, management, and prognosis of MLN differ from that of the proliferative forms of LN (Class III, IV, or Mixed III/IV + V). Although immunosuppressive therapy is often warranted in MLN, the optimal treatment regimen remains unclear. Here we describe the clinical presentation, histologic features, and natural history of MLN. We also review the role of supportive treatment and discuss when to deploy immunosuppressive management in MLN.


Assuntos
Membrana Basal Glomerular/patologia , Imunossupressores/farmacologia , Nefrite Lúpica , Humanos , Nefrite Lúpica/patologia , Nefrite Lúpica/fisiopatologia , Nefrite Lúpica/terapia , Síndrome Nefrótica/diagnóstico , Síndrome Nefrótica/etiologia , Prognóstico
13.
Acta Med Port ; 32(10): 635-640, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31625875

RESUMO

INTRODUCTION: Lupus nephritis is a serious complication of systemic lupus erythematosus. Currently, therapy is guided by findings in the renal biopsy, following the International Society of Nephrology / Renal Pathology Society classification. Austin and Hill's histomorphological indexes are not routinely obtained. In this retrospective single-centre study, we aimed to analyze the importance and applicability of the different morphological indexes in predicting response to treatment and prognosis. MATERIAL AND METHODS: Patients with kidney biopsy demonstrating lupus nephritis from the 2010 - 2016 period were included. We analyzed their demographic data, comorbidities, clinical presentation and laboratorial evaluation at the time of renal biopsy. We evaluated the following outcomes: clinical remission, renal function and proteinuria at end of follow-up. Histologic analysis was performed using the International Society of Nephrology / Renal Pathology Society classification and the morphological indexes described by Austin (Activity and Chronicity) and Hill. Univariate and multivariate statistical analysis was performed using STATA software. RESULTS: We analyzed 46 biopsy-proven lupus nephritis cases, with a median follow-up of 31.9 (13.2 - 45.6) months. Based on biopsy findings, 35 patients were started on immunosuppressive therapy. We observed that Class IV patients had, at presentation, lower estimated glomerular filtration rate (67.3 vs 94.6 mL/min; p = 0.02), higher proteinuria (4.26 vs 2.37 g/24 hours; p = 0.02) and a non-significantly higher C3 consumption (58.9 vs 77.4 mg/dL; p = 0.06). We did not observe correlations between International Society of Nephrology / Renal Pathology Society classification and the outcomes at the end of follow-up. In contrast, both the Hill biopsy index and Austin's Chronicity index were correlated with renal function and proteinuria at the end of follow-up. Austin's Activity index correlated with the immunological findings (C3, C4 and anti-dsDNA) at presentation. DISCUSSION: Because clinical activity poorly correlates with histologic activity, histological findings are fundamental when assessing patients with suspected lupus nephritis. The most recent International Society of Nephrology / Renal Pathology Society report supports the European League Against Rheumatism guidelines, encouraging the adoption of histomorphological indexes when evaluating lupus nephritis. Our data, showing a correlation between the renal outcomes and the indexes described by Austin and Hill, supports this view. CONCLUSION: The histomorphological indexes in lupus nephritis are easily obtainable, can predict renal outcomes and may help in the management of such patients.


Assuntos
Rim/patologia , Nefrite Lúpica/patologia , Nefrite Lúpica/terapia , Adulto , Análise de Variância , Biópsia , Complemento C3/metabolismo , Feminino , Seguimentos , Taxa de Filtração Glomerular , Humanos , Imunossupressores/uso terapêutico , Rim/fisiopatologia , Lúpus Eritematoso Sistêmico/complicações , Nefrite Lúpica/classificação , Nefrite Lúpica/fisiopatologia , Masculino , Prognóstico , Proteinúria/diagnóstico , Proteinúria/epidemiologia , Indução de Remissão , Estudos Retrospectivos , Resultado do Tratamento
14.
Lupus ; 28(13): 1549-1557, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31619143

RESUMO

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


Assuntos
Armadilhas Extracelulares/metabolismo , Proteína HMGB1/metabolismo , Lúpus Eritematoso Sistêmico/fisiopatologia , Nefrite Lúpica/fisiopatologia , Adulto , Estudos de Casos e Controles , Feminino , Proteína HMGB1/sangue , Humanos , Nefrite Lúpica/sangue , Masculino , Índice de Gravidade de Doença , Adulto Jovem
15.
Lupus ; 28(12): 1460-1467, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31594451

RESUMO

Whether the presence or absence of antiphospholipid antibodies (aPL) in patients with lupus nephritis (LN) is associated with differences in clinical outcomes remains unclear. We reviewed LN patients at a single centre during 2000-2017, and compared the clinical features and long-term outcomes between patients who were seropositive or seronegative for aPL. aPL was detected in 53/149 (35.6%) patients with biopsy-proven LN, and anticardiolipin IgM, anticardiolipin IgG, anti-ß2 glycoprotein I and lupus anticoagulant was detected in 18.8%, 18.1%, 10.7% and 8.1%, respectively. Follow-up was 155.8 ± 61.0 months, and was similar between aPL-seropositive and -seronegative patients. aPL seropositivity persisted in 94.3% of patients during remission. aPL-seropositive patients showed inferior patient survival (91% and 85% at 10 and 15 years, respectively, compared to 99% and 95% in aPL-seronegative patients; p = 0.043). Nine (6.0%) patients died during follow-up, including six aPL-seropositive (four thrombotic events and two bleeding complications related to anticoagulation) and three aPL-seronegative patients. aPL seropositivity was associated with more rapid decline in estimated glomerular filtration rate (-1.44 mL/min/year compared to -0.38 mL/min/year in aPL-seronegative patients; p = 0.027) and inferior long-term renal survival (82% and 74% at 10 and 15 years, respectively, compared to 91% and 87% in aPL-seronegative patients; p = 0.034). aPL-seropositive patients also had a higher incidence of thrombotic events and miscarriage (32.1% and 13.2%, respectively, compared to 16.7% and 2.1% in the aPL-seronegative group; p = 0.030 and 0.006). We concluded that aPL seropositivity was associated with inferior long-term patient and renal survival and more frequent thrombotic events and miscarriage in LN patients.


Assuntos
Anticorpos Antifosfolipídeos/imunologia , Síndrome Antifosfolipídica/complicações , Nefrite Lúpica/sangue , Nefrite Lúpica/patologia , Aborto Espontâneo/etiologia , Adulto , Anticorpos Anticardiolipina/imunologia , Anticorpos Antifosfolipídeos/sangue , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/tratamento farmacológico , Feminino , Taxa de Filtração Glomerular , Hemorragia/induzido quimicamente , Humanos , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Incidência , Rim/fisiopatologia , Inibidor de Coagulação do Lúpus/sangue , Nefrite Lúpica/epidemiologia , Nefrite Lúpica/fisiopatologia , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Gravidez , Trombose/induzido quimicamente , beta 2-Glicoproteína I/sangue
16.
Lupus ; 28(11): 1294-1301, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31583978

RESUMO

OBJECTIVES: Favourable long-term prognosis in proliferative lupus nephritis (LN) is associated with the achievement of complete renal response (CR), which is defined as a urine protein/creatinine ratio (UPCR) of < 0.5. However, it is unclear whether a more stringent cut-off for proteinuria (normal value of proteinuria; UPCR < 0.15) is better than CR. We aimed to evaluate the effect of stringent CR, defined as a UPCR of <0.15, on long-term renal outcomes in proliferative LN. METHODS: We included 87 patients with class III or IV LN who achieved CR at one year after induction therapy. Clinical and laboratory data were compared between the stringent and non-stringent CR groups. Logistic regression analysis was performed to identify factors associated with achievement of stringent CR. Cox analysis was performed to analyse the risk factors for renal flare and development of chronic kidney disease (CKD). RESULTS: The stringent and non-stringent CR groups included 58 and 29 patients, respectively. The two groups showed no significant baseline differences in terms of the clinical, laboratory and pathological classification. The sustained CR rates during five years were 91.3% and 50.0% (p = 0.014) in the stringent and non-stringent CR groups, respectively. In Cox analyses, the achievement of stringent CR was associated with a lower risk of five-year renal flare rate (hazard ratio (HR) = 0.161, 95% confidence interval (CI) 0.063-0.411, p < 0.01) and development of CKD (HR = 0.189, 95% CI 0.047-0.752, p = 0.018). Mycophenolate mofetil induction therapy was associated with achievement of stringent CR at a borderline level of significance (HR = 7.268, 95% CI 0.894-59.089, p = 0.064). CONCLUSION: Achievement of stringent CR predicted lower risk of renal flare and development of CKD in proliferative LN. These findings suggest that stringent CR is a valuable treatment target in proliferative LN.


Assuntos
Imunossupressores/administração & dosagem , Nefrite Lúpica/fisiopatologia , Ácido Micofenólico/administração & dosagem , Proteinúria/epidemiologia , Adulto , Feminino , Humanos , Nefrite Lúpica/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteinúria/etiologia , Indução de Remissão , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Adulto Jovem
17.
Lupus ; 28(13): 1598-1603, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31554458

RESUMO

INTRODUCTION: Systemic lupus erythematosus affects 4.8-78.5 people per 100,000 worldwide, 90% of whom are females. Geography and ethnicity have been shown to significantly affect the prevalence and natural history of the disease. Lupus nephritis affects around half of patients with systemic lupus erythematosus. Data about systemic lupus erythematosus and lupus nephritis in the Middle East are still scarce. In this study, we aimed to describe the characteristics of systemic lupus erythematosus and lupus nephritis at a tertiary care center in Lebanon. METHODS: This is a retrospective chart review of all biopsy-proven lupus nephritis patients admitted to the American University of Beirut medical center between January 2000 and December 2018. Patients above 12 years of age who had any International Society of Nephrology/Renal Pathology Society (ISN/RPS) class of lupus nephritis on their renal biopsy were included in the study. RESULTS: The study included 55 patients with lupus nephritis. Upon presentation of systemic lupus erythematosus, the most common clinical feature was arthritis, seen in 83% of patients, followed by anemia (82%) and malar rash (48%). In total 93% had positive ANA, 89% had positive anti-dsDNA and 98% of patients had proteinuria. The most common ISN/RPS class of lupus nephritis in our series was IV (49%). At the time of the biopsy 15% of patients underwent dialysis. At 6 months, 11/27 had complete remission, 6/27 had partial remission and 10/27 had no remission. At 1 year, 8/23 had complete remission, 4/23 had partial remission and 11/23 had no remission. During the study period, 15 out of 35 patients available for analysis had chronic kidney disease (CKD) and six out of 34 patients developed end-stage kidney disease requiring renal replacement therapy. In comparison to other series in the region, our series had more males affected, higher creatinine at the time of biopsy and greater degree of proteinuria. CONCLUSION: Our study provided insight on the demographics, characteristics, and outcomes of lupus nephritis in Lebanon. Interestingly, male gender was present in a quarter of patients. This warrants further investigation and confirmation. We are hoping to expand this experience into a national prospective registry to further characterize this entity in our region.


Assuntos
Falência Renal Crônica/etiologia , Lúpus Eritematoso Sistêmico/fisiopatologia , Nefrite Lúpica/fisiopatologia , Insuficiência Renal Crônica/etiologia , Adolescente , Adulto , Biópsia , Feminino , Humanos , Falência Renal Crônica/epidemiologia , Líbano , Lúpus Eritematoso Sistêmico/terapia , Nefrite Lúpica/terapia , Masculino , Pessoa de Meia-Idade , Diálise Renal/estatística & dados numéricos , Insuficiência Renal Crônica/epidemiologia , Estudos Retrospectivos , Centros de Atenção Terciária , Adulto Jovem
18.
Lupus ; 28(12): 1468-1472, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31551033

RESUMO

Signal transducer and activator of transcription (STAT) 3 is a regulator of T-cell responses to external stimuli, such as pro-inflammatory cytokines and chemokines. We have previously shown that STAT3 is activated (phosphorylated) at high levels in systemic lupus erythematosus (SLE) T cells and mediates chemokine-induced migration and T:B cell interactions. Stattic, a small molecular STAT3 inhibitor, can partially ameliorate lupus nephritis in mice. To understand the role of STAT3 better in T-cell pathophysiology in lupus nephritis and its potential as a treatment target, we silenced its expression in T cells using a cd4-driven CRE-Flox model. We found that lupus-prone mice that do not express STAT3 in T cells did not develop lymphadenopathy, splenomegaly, or glomerulonephritis. Moreover, the production of anti-dsDNA antibodies was decreased in these mice compared to controls. To dissect the mechanism, we also used a nephrotoxic serum model of nephritis. In this model, T cell-specific silencing of STAT3 resulted in amelioration of nephrotoxic serum-induced kidney damage. Taken together, our results suggest that in mouse models of autoimmune nephritis, T cell-specific silencing of STAT3 can hamper their ability to help B cells to produce autoantibodies and induce cell tissue infiltration. We propose that STAT3 inhibition in T cells represents a novel approach in the treatment of SLE and lupus nephritis in particular.


Assuntos
Lúpus Eritematoso Sistêmico/imunologia , Nefrite Lúpica/sangue , Fator de Transcrição STAT3/deficiência , Linfócitos T/metabolismo , Animais , Autoanticorpos/sangue , Quimiocinas/metabolismo , Óxidos S-Cíclicos/efeitos adversos , Óxidos S-Cíclicos/metabolismo , Citocinas/metabolismo , Humanos , Lúpus Eritematoso Sistêmico/patologia , Lúpus Eritematoso Sistêmico/terapia , Lúpus Eritematoso Sistêmico/veterinária , Nefrite Lúpica/fisiopatologia , Nefrite Lúpica/terapia , Nefrite Lúpica/veterinária , Camundongos , Camundongos Knockout/sangue , Camundongos Knockout/urina , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/farmacologia , Linfócitos T/patologia
19.
Lupus ; 28(9): 1111-1119, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31291845

RESUMO

BACKGROUND: Owing to the low prevalence of anti-neutrophil cytoplasmic antibodies (ANCA) in lupus nephritis (LN), there is no study about the differences between proteinase 3 (PR3)-ANCA positivity and myeloperoxidase (MPO)-ANCA positivity in LN until now. METHODS: Here we perform a retrospective study to determine whether there are differences in clinic-pathological characteristics and renal outcomes between PR3-ANCA-positive LN patients and MPO-ANCA-positive LN patients. RESULTS: A total of 26 (27.4%) PR3-ANCA-positive LN patients and 69 (72.6%) MPO-ANCA-positive LN patients (p < 0.001) were eligible for this study. Compared with PR3-ANCA-positive LN patients, MPO-ANCA-positive LN patients had significantly higher levels of serum creatinine (109.6 µmol/l vs. 74.3 µmol/l, p = 0.02), lower titers of antinuclear antibodies (ANA) (128 vs. 256, p = 0.01), and higher serum concentrations of C3 and C4 (0.54 g/l vs. 0.36 g/l, p = 0.002; 0.12 g/l vs. 0.06 g/l, p < 0.001; respectively). Furthermore, the MPO-ANCA-positive group had higher scores for chronicity index (p = 0.007), including interstitial fibrosis (p = 0.001) and tubular atrophy (p = 0.03) on biopsy specimens. The renal survival rates for MPO-ANCA-positive LN patients were 94.1% at 1 year, 83.2% at 5 years and 79.6% at 10 years; these values were worse when compared with those of the PR3-ANCA-positive group, which were 100%, 100% and 100%, respectively. CONCLUSION: MPO-ANCA-positive LN patients had more severely impaired baseline renal function and less active lupus serology. More severely chronic pathological changes, including interstitial fibrosis and tubular atrophy on renal specimens, occurred in MPO-ANCA-positive LN patients. We found that MPO-ANCA-positive LN patients had worse renal outcomes.


Assuntos
Anticorpos Anticitoplasma de Neutrófilos/imunologia , Nefrite Lúpica/fisiopatologia , Mieloblastina/imunologia , Peroxidase/imunologia , Adulto , Anticorpos Antinucleares/imunologia , Estudos de Coortes , Creatinina/sangue , Feminino , Seguimentos , Humanos , Nefrite Lúpica/imunologia , Masculino , Estudos Retrospectivos , Adulto Jovem
20.
Lupus ; 28(9): 1082-1090, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31296138

RESUMO

BACKGROUND: Few data are available about the rate of short-term remission and its impact on the long-term outcomes of proliferative lupus nephritis in the Middle East. METHODS: An observational study was carried out involving 96 adult patients with biopsy-proven focal or diffuse proliferative lupus nephritis (PLN) from four different hospitals. Data on induction, remission and long-term outcomes were collected and analyzed. RESULTS: Among the 96 patients with biopsy-proven PLN (median age 27 (IQR: 21,34) years, 85% women and median duration of systemic lupus erythematosus (SLE) prior to diagnosis 27 (IQR: 11, 55) months), 67% developed remission at 6 months (proportion 0.67; 95% CI 0.57, 0.76). Mycophenolate mofetil (MMF) was used in 45/96 (47%), CYC in 41/95 (43%) and other agents in 10/96 (10%). The choice of MMF as induction agent has increased in recent years. Among baseline characteristics, only histologic activity was found to have a significant association with remission, with active lesions more likely to remit than active/chronic and chronic lesions (AOR 6.5, 95% CI 1.44-29.39, p = 0.015). Based on Kaplan-Meier analysis, the 5-year renal survival rate without doubling serum creatinine was 73.8%. Compared to patients with complete remission, lower long-term renal survival rates were observed in patients with no remission (89.7 versus 43%, p = 0.001) and partial remission (89.7 versus 77.6%, p = 0.256). The cumulative rate of doubling serum creatinine, dialysis, relapse and death was 23%, 11%, 10% and 5%, respectively, at 48-month median follow up. CONCLUSION: Approximately two-thirds of patients with PLN develop remission in response to standard induction therapy. Remission was negatively associated with the presence of chronic changes in renal biopsy. Overall, MMF is the most commonly used agent to induce remission; however, with more severe disease CYC, is used more frequently. PLN is associated with significant long-term renal outcomes including a 26% cumulative rate of doubling of serum creatinine at 5 years. Initial remission predicts this long-term renal survival.


Assuntos
Creatinina/sangue , Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/complicações , Nefrite Lúpica/tratamento farmacológico , Adulto , Ciclofosfamida/uso terapêutico , Feminino , Humanos , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/fisiopatologia , Masculino , Ácido Micofenólico/uso terapêutico , Indução de Remissão , Estudos Retrospectivos , Arábia Saudita , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
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