RESUMEN
Anti-glomerular basement membrane (GBM) disease is a small-vessel vasculitis that represents the most aggressive form of autoimmune glomerulonephritis. The study aimed to investigate the prevalence, clinical characteristics, risk factors, and outcomes of anti-GBM disease through a systematic review and meta-analysis involving 47 studies with 2830 patients. The overall incidence of anti-GBM disease ranged from 0.60 to 1.79 per million population per annum. In rapidly progressive glomerulonephritis and crescentic glomerulonephritis, the pooled incidence rates were 8.0% and 12.8%, respectively. The pooled prevalence rates of anti-GBM antibodies, antineutrophil cytoplasmic antibodies (ANCA), and lung hemorrhage were 88.8%, 27.4%, and 32.6%, respectively. Patients with combined ANCA positivity demonstrated a prognosis comparable to those patients with only anti-GBM antibodies, though with differing clinical features. The pooled one-year patient and kidney survival rates were 76.2% and 30.2%, respectively. Kidney function on diagnosis and normal glomeruli percentage were identified as strong prognostic factors. This study represents the first comprehensive meta-analysis on anti-GBM disease, providing insights into its management. However, caution is warranted in interpreting some results due to the observational nature of the included studies and high heterogeneity.
Asunto(s)
Enfermedad por Anticuerpos Antimembrana Basal Glomerular , Humanos , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/epidemiología , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/inmunología , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/diagnóstico , Factores de Riesgo , Pronóstico , Incidencia , Anticuerpos Anticitoplasma de Neutrófilos/inmunología , Prevalencia , Autoanticuerpos/inmunología , Autoanticuerpos/sangreRESUMEN
Introduction: Anti-glomerular basement membrane (GBM) antibodies are pathogenic antibodies first detected in renal-limited anti-GBM disease and in Goodpasture disease, the latter characterized by rapidly progressive crescentic glomerulonephritis combined with intra-alveolar hemorrhage. Studies have suggested that anti-GBM antibody positivity may be of interest in lupus nephritis (LN). Moreover, severe anti-GBM vasculitis cases in patients with systemic lupus erythematosus (SLE) have been described in the literature, but few studies have assessed the incidence of anti-GBM antibodies in SLE patients. Objective: The main study objective was to determine if positive anti-GBM antibodies were present in the serum of SLE patients with or without proliferative renal damage and compared to a healthy control group. Methodology: This retrospective study was performed on SLE patients' sera from a Franco-German European biobank, developed between 2011 and 2014, from 17 hospital centers in the Haut-Rhin region. Patients were selected according to their renal involvement, and matched by age and gender. The serum from healthy voluntary blood donors was also tested. Anti-GBM were screened by fluorescence enzyme immunoassay (FEIA), and then by indirect immunofluorescence (IIF) in case of low reactivity detection (titer >6 U/ml). Results: The cohort was composed of 100 SLE patients with proliferative LN (27% with class III, 67% with class IV, and 6% with class V), compared to 100 SLE patients without LN and 100 controls. Patients were mostly Caucasian and met the ACR 1997 criteria and/or the SLICC 2012 criteria. Among the 300 tested sera, no significant levels of anti-GBM antibodies were detected (>10 U/ml) by the automated technique, three sera were found "ambivalent" (>7 U/ml): one in the SLE with LN group and two in the SLE without LN group. Subsequent IIF assays did not detect anti-GBM antibodies. Conclusion: Anti-GBM antibodies were not detected in the serum of Caucasian patients with SLE, even in case of renal involvement, a situation favoring the antigenic exposure of glomerular basement membranes. Our results reaffirm the central role of anti-GBM antibodies as a specific diagnostic biomarker for Goodpasture vasculitis and therefore confirm that anti-GBM antibody must not be carried out in patients with SLE (with or without LN) in the absence of disease-suggestive symptoms.
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Autoanticuerpos/inmunología , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/inmunología , Nefritis Lúpica/etiología , Adulto , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/sangre , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/epidemiología , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/inmunología , Autoanticuerpos/sangre , Biomarcadores , Estudios de Casos y Controles , Femenino , Humanos , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/epidemiología , Nefritis Lúpica/diagnóstico , Nefritis Lúpica/epidemiología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Índice de Severidad de la EnfermedadAsunto(s)
Enfermedad por Anticuerpos Antimembrana Basal Glomerular/epidemiología , Anticuerpos Antivirales/sangre , Betacoronavirus/inmunología , Infecciones por Coronavirus/complicaciones , Neumonía Viral/complicaciones , Glicoproteína de la Espiga del Coronavirus/inmunología , Inmunidad Adaptativa , Adulto , Anciano , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/diagnóstico , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/inmunología , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/virología , Anticuerpos Antivirales/inmunología , Betacoronavirus/genética , Betacoronavirus/aislamiento & purificación , COVID-19 , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/virología , Femenino , Membrana Basal Glomerular/inmunología , Membrana Basal Glomerular/patología , Humanos , Incidencia , Londres/epidemiología , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/epidemiología , Neumonía Viral/inmunología , Neumonía Viral/virología , ARN Viral/aislamiento & purificación , SARS-CoV-2RESUMEN
Introducción: El síndrome de Goodpasture es una rara enfermedad autoinmune que forma parte del espectro de síndrome pulmón-riñón Objetivo: Presentar un paciente pediátrico con síndrome de Goodpasture atípico. Presentación del caso: Paciente de seis años seguida por el servicio de nefrología; ingresó a los cuatro años de edad por presentar hematuria macroscópica asociada a manifestaciones respiratorias y antecedente de títulos elevados de anticuerpos antimembrana basal glomerular. Fue motivo de investigación y se diagnosticó el síndrome de Goodpasture. Después de tratamiento inmunosupresor con ciclofosfamida y metilprednisolona seguido de prednisona oral, la paciente presentó descenso de los títulos de anticuerpos antimembrana basal glomerular, así como mejoría de los síntomas respiratorios, sin embargo, la proteinuria se mantuvo con incremento en los últimos meses. Para el diagnóstico se tuvieron en cuenta las manifestaciones clínicas en la niña, título elevado de anticuerpos antimembrana basal glomerular y la confirmación por biopsia renal de glomerulopatía. El tratamiento fue rápidamente efectivo con una disminución inmediata en los títulos de anticuerpos antimembrana basal y mejoría evidente de la condición clínica de la paciente. Se trata del primer caso pediátrico con síndrome de Goodpasture publicado en Cuba. Conclusiones: Por tratarse de una entidad rara en pediatría se requiere un diagnóstico temprano y tratamiento agresivo para mejorar el pronóstico del paciente. En su seguimiento son necesarias una terapia farmacológica prolongada, una adecuada adherencia al tratamiento propuesto y un estrecho monitoreo clínico y analítico de lo cual dependerá la progresión de la injuria renal y pulmonar(AU)
Introduction: Goodpasture´s syndrome is a rare autoimmune disease that is part of the lung-kidney syndrome's sprectrum. Objective: To present the case of a pediatric patient with an atypical Goodpasture´s syndrome. Case presentation: Six years old female patient under follow-up in the Nephrology service. She was admitted when she was four years old by presenting macroscopic hematuria, respiratory symptoms and a history of high titers of anti-glomerular basement membrane antibodies. She was under research and was diagnosed with the Goodpasture´s symdrome. After being under immunosupressive treatment with cyclophosphamide and methylprednisolone followed by oral prednisone, the patient presented a decrease in the titers of anti-glomerular basement membrane antibodies, and an improvement of the respiratory symptoms; however, proteinuria kept increasing in the last months. For the diagnosis, there were taken into account the clinical manifestations of the girl, the high titers of anti-glomerular basement membrane antibodies and the confirmations of glumerulopathy by renal biopsy. The treatment was effective quickly with an inmmediate decrease of the titers of anti-glomerular basement membrane antibodies and an evident improvement of the clinical condition of the patient. This is the first pediatric case presenting Goodpasture´s syndrome that has been published in Cuba. Conclusions: As this is a rare entity in Pediatrics, it is required an early diagnosis and an aggressive treatment to improve the patient's prognosis. In the follow-up are needed a prolonged pharmacological therapy, an adequate adherence to the proposed treatment and a close clinical and analytic monitoring from which will depend the progression of the lung and renal injury(AU)
Asunto(s)
Humanos , Femenino , Preescolar , Niño , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/diagnóstico , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/epidemiologíaRESUMEN
ABSTRACT Background and objectives: Anti-neutrophil cytoplasmic autoantibodies (ANCA) associated vasculitis is a small vessel vasculitis with insufficient epidemiologic estimates in the United States. We aimed to determine demographic and clinical features of ANCA associated vasculitis patients presenting to a large tertiary care referral center in Upstate New York. Design, setting, participants, and measurements: A retrospective analysis of cases with pauci-immune GN on renal biopsy and clinical diagnosis of ANCA vasculitis presenting over 11 years was conducted. Outcomes of interest were: demographics, ANCA antibody positivity, patient and renal survival, and regional trends. Results: 986 biopsies were reviewed, 41 cases met the criteria for inclusion: 18 GPA, 19 MPA, and 4 double positive (anti-GBM disease plus ANCA vasculitis). Mean age at presentation was 52.4 years (SD 23.7), 23 (56%) were male and median creatinine was 2.6 mg/dL. The median patient follow up was 77 weeks (IQR 10 - 263 weeks), with a 3-month mortality rate of 5.7% and a 1-year estimated mortality rate of 12%. Thirteen patients required hemodialysis at the time of diagnosis; 7 patients came off dialysis, with median time to renal recovery of 4.86 weeks (IQR 1.57 - 23.85 weeks). C-ANCA positivity (p < 0.001) and C-ANCA plus PR3 antibody pairing (p = 0.005) was statistically significant in GPA versus MPA. P-ANCA positivity was observed in MPA versus GPA (p = 0.02) and double positive versus GPA (p = 0.002), with P-ANCA and MPO antibody pairing in MPA versus GPA (p = 0.044). Thirty-seven of the 41 cases were referred locally, 16 cases were from within a 15-mile radius of Albany, Schenectady, and Saratoga counties. Conclusions: ANCA vasculitis is associated with end stage renal disease and increased mortality. Our study suggests the possibility of higher regional incidence of pauci-immune GN in Upstate New York. Further studies should investigate the causes of clustering of cases to specific regions.
RESUMO Introdução e objetivos: A vasculite associada a anticorpos anticitoplasma de neutrófilo (ANCA) é uma vasculite de pequenos vasos com estimativas epidemiológicas insuficientes nos Estados Unidos. Nosso objetivo foi determinar características demográficas e clínicas de pacientes com vasculite associada à ANCA, apresentando-se a um grande centro de referência de atendimento terciário em Upstate New York. Formato, cenário, participantes e medidas: Foi realizada uma análise retrospectiva dos casos de GN pauci-imune em biópsias renais e diagnóstico clínico de vasculite ANCA por mais de 11 anos. Os resultados de interesse foram: dados demográficos, positividade de anticorpos ANCA, sobrevidas renal e de pacientes e tendências regionais. Resultados: 986 biópsias foram revisadas, 41 casos preencheram os critérios de inclusão: 18 GPA, 19 PAM, e 4 duplo-positivos (doença anti-MBG com vasculite ANCA). A média de idade na apresentação foi de 52,4 anos (DP 23,7), 23 (56%) eram do sexo masculino e mediana de creatinina de 2,6 mg/dL. O acompanhamento mediano dos pacientes foi de 77 semanas (IQR 10 - 263 semanas), com uma taxa de mortalidade de 3 meses de 5,7% e uma taxa de mortalidade estimada em 1 ano de 12%. Treze pacientes necessitaram de hemodiálise no momento do diagnóstico; 7 pacientes saíram da diálise, com tempo médio para recuperação renal de 4,86 semanas (IQR 1,57 - 23,85 semanas). A positividade para C-ANCA (p < 0,001) e o pareamento de anticorpos C-ANCA mais PR3 (p = 0,005) foram estatisticamente significantes em GPA versus PAM. A positividade de P-ANCA foi observada em PAM versus GPA (p = 0,02) e duplo positivo versus GPA (p = 0,002), com pareamento de anticorpos P-ANCA e MPO em PAM versus GPA (p = 0,044). Trinta e sete dos 41 casos foram encaminhados localmente, 16 casos foram de dentro de um raio de 15 milhas dos condados de Albany, Schenectady e Saratoga. Conclusões: A vasculite por ANCA está associada à doença renal terminal e aumento da mortalidade. Nosso estudo sugere a possibilidade de maior incidência regional de GN pauci-imune no norte do estado de Nova York. Novos estudos devem investigar as causas do acúmulo de casos em regiões específicas.
Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , Atención Terciaria de Salud , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/epidemiología , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/mortalidad , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/epidemiología , Fallo Renal Crónico/epidemiología , Biopsia , Comorbilidad , New York/epidemiología , Incidencia , Estudios Retrospectivos , Estudios de Seguimiento , Mortalidad/tendencias , Diálisis Renal , Anticuerpos Anticitoplasma de Neutrófilos/sangre , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/sangre , Creatinina/sangre , Estimación de Kaplan-Meier , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/sangre , Riñón/patología , Fallo Renal Crónico/sangreRESUMEN
BACKGROUND AND OBJECTIVES: Anti-neutrophil cytoplasmic autoantibodies (ANCA) associated vasculitis is a small vessel vasculitis with insufficient epidemiologic estimates in the United States. We aimed to determine demographic and clinical features of ANCA associated vasculitis patients presenting to a large tertiary care referral center in Upstate New York. Design, setting, participants, and measurements: A retrospective analysis of cases with pauci-immune GN on renal biopsy and clinical diagnosis of ANCA vasculitis presenting over 11 years was conducted. Outcomes of interest were: demographics, ANCA antibody positivity, patient and renal survival, and regional trends. RESULTS: 986 biopsies were reviewed, 41 cases met the criteria for inclusion: 18 GPA, 19 MPA, and 4 double positive (anti-GBM disease plus ANCA vasculitis). Mean age at presentation was 52.4 years (SD 23.7), 23 (56%) were male and median creatinine was 2.6 mg/dL. The median patient follow up was 77 weeks (IQR 10 - 263 weeks), with a 3-month mortality rate of 5.7% and a 1-year estimated mortality rate of 12%. Thirteen patients required hemodialysis at the time of diagnosis; 7 patients came off dialysis, with median time to renal recovery of 4.86 weeks (IQR 1.57 - 23.85 weeks). C-ANCA positivity (p < 0.001) and C-ANCA plus PR3 antibody pairing (p = 0.005) was statistically significant in GPA versus MPA. P-ANCA positivity was observed in MPA versus GPA (p = 0.02) and double positive versus GPA (p = 0.002), with P-ANCA and MPO antibody pairing in MPA versus GPA (p = 0.044). Thirty-seven of the 41 cases were referred locally, 16 cases were from within a 15-mile radius of Albany, Schenectady, and Saratoga counties. CONCLUSIONS: ANCA vasculitis is associated with end stage renal disease and increased mortality. Our study suggests the possibility of higher regional incidence of pauci-immune GN in Upstate New York. Further studies should investigate the causes of clustering of cases to specific regions.
Asunto(s)
Enfermedad por Anticuerpos Antimembrana Basal Glomerular/epidemiología , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/epidemiología , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/mortalidad , Fallo Renal Crónico/epidemiología , Atención Terciaria de Salud , Adulto , Anciano , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/sangre , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/sangre , Anticuerpos Anticitoplasma de Neutrófilos/sangre , Biopsia , Comorbilidad , Creatinina/sangre , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Estimación de Kaplan-Meier , Riñón/patología , Fallo Renal Crónico/sangre , Masculino , Persona de Mediana Edad , Mortalidad/tendencias , New York/epidemiología , Diálisis Renal , Estudios RetrospectivosRESUMEN
Patients with both anti-glomerular basement membrane (anti-GBM) disease and Castleman disease have been rarely reported. In this study, we report 3 patients with this combination. They had immunologic features similar to patients with classic anti-GBM disease. Sera from the 3 patients recognized the noncollagenous (NC) domain of the α3 chain of type IV collagen (α3(IV)NC1) and its 2 major epitopes, EA and EB. All 4 immunogloblin G (IgG) subclasses against α3(IV)NC1 were detectable, with predominance of IgG1. In one patient with lymph node biopsy specimens available, sporadic plasma cells producing α3(IV)NC1-IgG were found, suggesting a causal relationship between the 2 diseases. One patient, who achieved remission with antibody clearance and normalization of serum creatinine and interleukin 6 concentrations after plasma exchange and 3 cycles of chemotherapy, experienced recurrence of anti-GBM antibodies and an increase in interleukin 6 concentration after chemotherapy discontinuation because of adverse effects, but both returned to normal after another cycle of chemotherapy. This clinical course and the pathologic findings support the hypothesis that the Castleman disease-associated tumor cells are the source of the anti-GBM autoantibodies.
Asunto(s)
Enfermedad por Anticuerpos Antimembrana Basal Glomerular/epidemiología , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/terapia , Autoantígenos/inmunología , Enfermedad de Castleman/epidemiología , Enfermedad de Castleman/terapia , Adulto , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/inmunología , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/patología , Biopsia con Aguja , Enfermedad de Castleman/inmunología , Enfermedad de Castleman/patología , Colágeno Tipo IV/inmunología , Colágeno Tipo IV/metabolismo , Terapia Combinada , Comorbilidad , Epítopos , Estudios de Seguimiento , Hospitalización , Humanos , Inmunoglobulina G/inmunología , Inmunohistoquímica , Masculino , Metilprednisolona/uso terapéutico , Persona de Mediana Edad , Intercambio Plasmático/métodos , Quimioterapia por Pulso , Enfermedades Raras , Muestreo , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
AIM: Anti-glomerular basement membrane (GBM) disease is an autoimmune disorder with rapidly progressive glomerulonephritis and alveolar haemorrhage. Fever symptoms and prodromal infections have been reported in many cases, but still not been elucidated. METHODS: Our study enrolled 140 consecutive patients with anti-GBM disease and retrospectively analyzed the characteristics of fever symptoms and the possible reasons. RESULTS: Among the 140 patients, 94 (67.1%) patients presented with fever (over 37.5°C) prior to admission or within 48 h of hospitalization. Among those with fever, 74 (78.7%) patients had infections, 15 (16.0%) patients had positive serum anti-neutrophil cytoplasmic antibodies, all towards myeloperoxidase, which was comparable to the patients without fever (17.4%, P = 0.830). There were 93/140 patients suffered from infections, with 47.3% in lungs and 31.2% on upper respiratory tract. In some cases, we identified the microbes of infections, including Candida albicans, Escherichia coli, Acinetobacter baumannii, Enterococcus faecalis, Klebsiella pneumoniae, Hemolytic staphylococci, Pseudomonas aeruginosa and Citrobacter braakii. Patients with fever had higher levels of serum anti-GBM antibodies (154.9 ± 58.4 vs. 106.0 ± 63.2 IU/mL, P < 0.001), higher serum creatinine (733.4 ± 402.5 vs. 580.6 ± 368.1 µmol/L, P = 0.032), higher percentage of crescents (87.0 ± 15.6 vs. 67.4 ± 37.6%, P = 0.021), and higher frequency of progression to end stage renal disease (ESRD) (80.9% vs. 60.9%, P = 0.011). CONCLUSION: We concluded that fever is a common symptom in anti-GBM disease and associates with more severe glomerulonephritis. The majority of patients at presentation had fever with respiratory tract infections, which needs further investigation to reveal their role in the pathogenesis of anti-GBM disease.
Asunto(s)
Enfermedad por Anticuerpos Antimembrana Basal Glomerular/epidemiología , Fiebre/epidemiología , Infecciones del Sistema Respiratorio/epidemiología , Adulto , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/diagnóstico , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/inmunología , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/terapia , Biomarcadores/sangre , China/epidemiología , Progresión de la Enfermedad , Femenino , Fiebre/diagnóstico , Fiebre/inmunología , Fiebre/terapia , Humanos , Fallo Renal Crónico/epidemiología , Masculino , Persona de Mediana Edad , Prevalencia , Síntomas Prodrómicos , Pronóstico , Infecciones del Sistema Respiratorio/diagnóstico , Infecciones del Sistema Respiratorio/inmunología , Infecciones del Sistema Respiratorio/terapia , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Factores de TiempoRESUMEN
BackgroundIn an attempt to improve knowledge about childhood Goodpasture's disease, we performed a retrospective analysis of patients with Goodpasture's disease from several pediatric nephrology centers.MethodsWe analyzed the responses to 27 questions that elicited information about the following: incidence, demographics, patient history and clinical presentation, diagnostics performed, acute and chronic therapy, course of disease, and outcome.ResultsGoodpasture's disease, which is extremely rare in this age group, may manifest in 2-year-old toddlers and does not typically present with pulmonary findings before puberty. Goodpasture's disease has a poor outcome with more than 50% of patients progressing to end-stage renal disease. No deaths were reported in this cohort, and renal improvement was observed in children with severe biopsy findings who required renal replacement therapy during the acute phase.ConclusionThe present investigation gives detailed information about childhood Goodpasture's disease under real-life conditions and reveals that very few pediatric cases have been reported. Nearly 50% of children progressed to end-stage renal disease. However, long-term outcome in children might be better than in adults. Aggressive immunosuppressive therapy might be necessary for all affected children, even in patients who require renal replacement therapy or have severe biopsy findings.
Asunto(s)
Enfermedad por Anticuerpos Antimembrana Basal Glomerular/epidemiología , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/terapia , Inmunosupresores/uso terapéutico , Adolescente , Corticoesteroides/uso terapéutico , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/diagnóstico , Biopsia , Niño , Preescolar , Ciclofosfamida/uso terapéutico , Femenino , Humanos , Incidencia , Fallo Renal Crónico/etiología , Masculino , Nefrología , Pediatría , Plasmaféresis , Prevalencia , Terapia de Reemplazo Renal , Estudios Retrospectivos , Factores de Riesgo , Encuestas y Cuestionarios , Resultado del TratamientoRESUMEN
Anti-glomerular basement membrane (anti-GBM) disease is a rare small vessel vasculitis that affects the capillary beds of the kidneys and lungs. It is an archetypic autoimmune disease, caused by the development of directly pathogenic autoantibodies targeting a well characterized autoantigen expressed in the basement membranes of these organs, although the inciting events that induce the autoimmune response are not fully understood. The recent confirmation of spatial and temporal clustering of cases suggests that environmental factors, including infection, may trigger disease in genetically susceptible individuals. The majority of patients develop widespread glomerular crescent formation, presenting with features of rapidly progressive GN, and 40%-60% will have concurrent alveolar hemorrhage. Treatment aims to rapidly remove pathogenic autoantibody, typically with the use of plasma exchange, along with steroids and cytotoxic therapy to prevent ongoing autoantibody production and tissue inflammation. Retrospective cohort studies suggest that when this combination of treatment is started early, the majority of patients will have good renal outcome, although presentation with oligoanuria, a high proportion of glomerular crescents, or kidney failure requiring dialysis augur badly for renal prognosis. Relapse and recurrent disease after kidney transplantation are both uncommon, although de novo anti-GBM disease after transplantation for Alport syndrome is a recognized phenomenon. Copresentation with other kidney diseases such as ANCA-associated vasculitis and membranous nephropathy seems to occur at a higher frequency than would be expected by chance alone, and in addition atypical presentations of anti-GBM disease are increasingly reported. These observations highlight the need for future work to further delineate the immunopathogenic mechanisms of anti-GBM disease, and how to better refine and improve treatments, particularly for patients presenting with adverse prognostic factors.
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Enfermedad por Anticuerpos Antimembrana Basal Glomerular , Glomérulos Renales , Animales , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/diagnóstico , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/epidemiología , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/inmunología , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/terapia , Autoanticuerpos/inmunología , Autoinmunidad , Humanos , Inmunosupresores/uso terapéutico , Glomérulos Renales/efectos de los fármacos , Glomérulos Renales/inmunología , Glomérulos Renales/patología , Trasplante de Riñón , Intercambio Plasmático , Valor Predictivo de las Pruebas , Recurrencia , Factores de Riesgo , Esteroides/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND AND OBJECTIVES: An environmental trigger has been proposed as an inciting factor in the development of anti-GBM disease. This multicenter, observational study sought to define the national incidence of anti-GBM disease during an 11-year period (2003-2014) in Ireland, investigate clustering of cases in time and space, and assess the effect of spatial variability in incidence on outcome. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We ascertained cases by screening immunology laboratories for instances of positivity for anti-GBM antibody and the national renal histopathology registry for biopsy-proven cases. The population at risk was defined from national census data. We used a variable-window scan statistic to detect temporal clustering. A Bayesian spatial model was used to calculate standardized incidence ratios (SIRs) for each of the 26 counties. RESULTS: Seventy-nine cases were included. National incidence was 1.64 (95% confidence interval [95% CI], 0.82 to 3.35) per million population per year. A temporal cluster (n=10) was identified during a 3-month period; six cases were resident in four rural counties in the southeast. Spatial analysis revealed wide regional variation in SIRs and a cluster (n=7) in the northwest (SIR, 1.71; 95% CI, 1.02 to 3.06). There were 29 deaths and 57 cases of ESRD during a mean follow-up of 2.9 years. Greater distance from diagnosis site to treating center, stratified by median distance traveled, did not significantly affect patient (hazard ratio, 1.80; 95% CI, 0.87 to 3.77) or renal (hazard ratio, 0.76; 95% CI, 0.40 to 1.13) survival. CONCLUSIONS: To our knowledge, this is the first study to report national incidence rates of anti-GBM disease and formally investigate patterns of incidence. Clustering of cases in time and space supports the hypothesis of an environmental trigger for disease onset. The substantial variability in regional incidence highlights the need for comprehensive country-wide studies to improve our understanding of the etiology of anti-GBM disease.
Asunto(s)
Enfermedad por Anticuerpos Antimembrana Basal Glomerular/epidemiología , Fallo Renal Crónico/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/etiología , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/mortalidad , Análisis por Conglomerados , Exposición a Riesgos Ambientales/efectos adversos , Femenino , Humanos , Incidencia , Irlanda/epidemiología , Fallo Renal Crónico/etiología , Masculino , Persona de Mediana Edad , Análisis Espacio-Temporal , Tasa de SupervivenciaRESUMEN
The overall and renal outcomes of patients with Goodpasture syndrome (GS), a rare autoimmune disorder characterized by circulating anti-GBM antibodies and rapidly progressive glomerulonephritis and/or pulmonary hemorrhage, have mostly been reported in small-sized cohorts or by aggregating patients receiving a variety of therapies that include aggressive (i.e., combined plasma exchanges, corticosteroids, and cyclophosphamide) and less aggressive (i.e., either plasma exchanges or immunosuppressive drugs, or no treatment). To address the prognosis of GS patients with relatively homogeneous management including plasma exchanges, we conducted a multicenter retrospective study on GS patients included in the registry of the French Society of Hemapheresis. 122 patients were included (kidney alone (n = 28), lung alone (n = 5), or combined involvement (n = 89)). All 122 patients received plasma exchanges (median number of sessions: 13 [9-17]), either alone (n = 8) or associated with combined corticosteroids and oral or IV cyclophosphamide (n = 101) or with corticosteroids alone (n = 12) or cyclophosphamide alone (n = 2). One-year survival was 86.9%. 7/16 patients died from severe infection. In multivariate analyses (Cox's regression model), being aged <60 years, and number of plasma exchanges were correlated to overall survival. The use of alternative immunosuppressive drugs (because of refractory or relapsing GS) was correlated to mortality at one year. Superiority of oral cyclophosphamide compared to intravenous intake was close to significant. Using a logistic regression model, renal survival in patients alive at 1 year was only predicted by serum creatinine <500 µmol/L at presentation. This large series describes the predictive factors for overall and renal survival of GS patients treated by plasma exchanges. Interventional studies that compare oral and intravenous cyclophosphamide, as well as testing new immunosuppressive therapies, are warranted.
Asunto(s)
Enfermedad por Anticuerpos Antimembrana Basal Glomerular/epidemiología , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/terapia , Inmunosupresores/uso terapéutico , Sistema de Registros/estadística & datos numéricos , Corticoesteroides/uso terapéutico , Adulto , Anciano , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/sangre , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/complicaciones , Autoanticuerpos/sangre , Creatinina/sangre , Ciclofosfamida/uso terapéutico , Femenino , Humanos , Incidencia , Estimación de Kaplan-Meier , Riñón/inmunología , Riñón/patología , Pulmón/inmunología , Pulmón/patología , Masculino , Persona de Mediana Edad , Intercambio Plasmático , Pronóstico , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND AND OBJECTIVES: Antiglomerular basement membrane autoantibodies are pathogenic in antiglomerular basement membrane disease with two major epitopes, E(A) and E(B), on α3 chain of type IV collagen. This study investigated the epitope spectrum of antiglomerular basement membrane autoantibodies, aiming to identify the association between epitope specificity and kidney injury. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: All 108 patients with antiglomerular basement membrane disease and complete clinical data were divided into three groups according to renal dysfunction: mild group (n=20) with serum creatitine≤1.5 mg/dl; moderate group (n=22) with serum creatinine=1.5-6.8 mg/dl; severe group (n=66) with serum creatitine≥6.8 mg/dl. Epitope spectrums of antibodies were determined by ELISA, and their associations with kidney damage were analyzed. Sequential serum samples in 40 patients were examined during disease courses. RESULTS: E(A) and E(B) were recognized in 79.6% and 72.2% of patients, respectively. E(A) and E(B) reactions were the lowest in the mild group and higher in the moderate group (E(A): 35.0% versus 81.8%, P=0.002; E(B): 15.0% versus 68.2%, P=0.001). They were the highest in the severe group (E(A): 92.4%, P=0.31; E(B): 90.9%, P=0.02). Close association was observed between renal injury and E(A) and E(B) reactions. Multivariate Cox regression analysis showed that E(B) reaction was an independent risk factor for renal failure (hazard ratio=6.91, P=0.02). The recognition for non-E(AB) remained low among groups. No augmentation of epitope spectrum was shown in serial serum samples. CONCLUSIONS: Intramolecular epitope spreading might occur before the onset of human antiglomerular basement membrane disease. The autoimmunity to E(A) and E(B), especially E(B), was crucial for kidney dysfunction.
Asunto(s)
Enfermedad por Anticuerpos Antimembrana Basal Glomerular/epidemiología , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/inmunología , Autoanticuerpos/sangre , Autoantígenos/inmunología , Colágeno Tipo IV/inmunología , Epítopos/inmunología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/mortalidad , Especificidad de Anticuerpos/inmunología , Ensayo de Inmunoadsorción Enzimática , Femenino , Células HEK293 , Humanos , Estimación de Kaplan-Meier , Riñón/inmunología , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Modelos de Riesgos Proporcionales , Estudios Seroepidemiológicos , Adulto JovenRESUMEN
Anti-glomerular basement membrane (GBM) disease usually presents with rapidly progressive glomerulonephritis accompanied by pulmonary hemorrhage. The low incidence and fulminant course of disease preclude a large randomized controlled study to define the benefits of any given therapy. We conducted a retrospective survey of 221 consecutive patients seen from 1998 to 2008 in our hospital, and report here the patient and renal survival and the risk factors affecting the outcomes. Considering the similar clinical features of the patients, we could compare the effects of 3 different treatment regimens: 1) combination therapy of plasmapheresis and immunosuppression, 2) steroids and cytotoxic agents, and 3) steroids alone.The patient and renal survival rates were 72.7% and 25.0%, respectively, at 1 year after disease presentation. The serum level of anti-GBM antibodies (increased by 20 U/mL; hazard ratio [HR], 1.16; p = 0.009) and the presentation of positive antineutrophil cytoplasmic antibodies (ANCA) (HR, 2.18; p = 0.028) were independent predictors for patient death. The serum creatinine at presentation (doubling from 1.5 mg/dL; HR, 2.07; p < 0.001) was an independent predictor for renal failure.The combination therapy of plasmapheresis plus corticosteroids and cyclophosphamide had an overall beneficial effect on both patient survival (HR for patient mortality, 0.31; p = 0.001) and renal survival (HR for renal failure, 0.60; p = 0.032), particularly patient survival for those with Goodpasture syndrome (HR for patient mortality, 0.29; p = 0.004) and renal survival for those with anti-GBM nephritis with initial serum creatinine over 6.8 mg/dL (HR for renal failure, 0.52; p = 0.014). The treatment with corticosteroids plus cyclophosphamide was found not to improve the renal outcome of disease (p = 0.73). In conclusion, the combination therapy was preferred for patients with anti-GBM disease, especially those with pulmonary hemorrhage or severe renal damage. Early diagnosis was crucial to improving outcomes.
Asunto(s)
Enfermedad por Anticuerpos Antimembrana Basal Glomerular/terapia , Anticuerpos Anticitoplasma de Neutrófilos/inmunología , Glucocorticoides/uso terapéutico , Inmunosupresores/uso terapéutico , Plasmaféresis/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/epidemiología , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/inmunología , Anticuerpos Anticitoplasma de Neutrófilos/sangre , Niño , China/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de Supervivencia/tendencias , Resultado del Tratamiento , Adulto JovenRESUMEN
This review focuses on the epidemiological characteristics and etiologies of four primary systemic vasculitides with frequent lung involvement, namely Wegener granulomatosis (WG), microscopic polyangiitis (MPA), Churg-Strauss syndrome (CSS), and Goodpasture syndrome (GPS). Elucidation of the mechanisms underlying these vasculitides with frequent lung involvement is complicated by their rarity, which hampers the undertaking of large-scale studies; difficulties in classification; and their multifaceted clinical presentations, which infer the existence of several etiologic pathways. Notwithstanding, epidemiological research showed some evidence for international, interethnic, and temporal variations of the frequencies of these four vasculitides; led to the identification of several genetic and environmental risk factors; and provided insight on the extent to which genes and environment might contribute to their development. Available data support the concept that WG, MPA, CSS, and GPS have unique and shared risk determinants. Although the precise causes of these vasculitides are not yet fully understood and the development of prevention strategies is out of our reach at present, current knowledge enables the formulation of etiologic hypotheses to provide caregivers and their patients with valuable information on the nature of these rare entities.
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Enfermedad por Anticuerpos Antimembrana Basal Glomerular/epidemiología , Alveolos Pulmonares/patología , Vasculitis Sistémica/epidemiología , Vasculitis Sistémica/etiología , Adolescente , Adulto , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/complicaciones , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/etiología , Síndrome de Churg-Strauss/complicaciones , Síndrome de Churg-Strauss/epidemiología , Síndrome de Churg-Strauss/etiología , Comparación Transcultural , Granulomatosis con Poliangitis/complicaciones , Granulomatosis con Poliangitis/epidemiología , Granulomatosis con Poliangitis/etiología , Hemorragia/epidemiología , Hemorragia/etiología , Humanos , Incidencia , Poliangitis Microscópica/complicaciones , Poliangitis Microscópica/epidemiología , Poliangitis Microscópica/etiología , Prevalencia , Vasculitis Sistémica/complicaciones , Adulto JovenAsunto(s)
Envejecimiento/inmunología , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/epidemiología , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/inmunología , Anticuerpos Anticitoplasma de Neutrófilos/inmunología , Anticuerpos/sangre , Membrana Basal Glomerular/inmunología , Anciano , Anciano de 80 o más Años , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/terapia , China , Humanos , Hidrocarburos/efectos adversos , Exposición Profesional/efectos adversos , Intercambio Plasmático , Factores de RiesgoAsunto(s)
Enfermedad por Anticuerpos Antimembrana Basal Glomerular/epidemiología , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/epidemiología , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/complicaciones , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/inmunología , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/complicaciones , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/inmunología , China/epidemiología , Glomerulonefritis/epidemiología , Glomerulonefritis/etiología , Humanos , IncidenciaRESUMEN
The second most common cause of chronic renal failure is glomerulonephritis, which is a collective term used for numerous diseases with the common denominator of histological renal inflammation emanating from the glomerular tuft. Whether all forms of glomerulonephritis should be considered as autoimmune disease is debatable, but immune mechanisms are important in all of them. This review focuses on four relatively well delineated forms of primary glomerulonephritis: Goodpastures or anti-GBM disease, IgA nephritis, membranous nephropathy and membranoproliferative glomerulonephritis. The autoantibodies are directed either to molecules within the glomeruli, such as the glomerular basement membrane in anti-GBM disease and to the podocytes in membranous glomerulonephritis, or to components of the immune system such as C3 convertase in membranoproliferative glomerulonephritis and IgA in IgA nephritis. Differences in diagnostic practices and classification controversies obscure comparative epidemiological studies, but there seem to be huge differences between incidence rates between countries and over time, both genetic factors and infections seem to matter but strong indications for a role of other environmental factors are still lacking.
Asunto(s)
Enfermedad por Anticuerpos Antimembrana Basal Glomerular/epidemiología , Enfermedades Autoinmunes/epidemiología , Glomerulonefritis Membranoproliferativa/epidemiología , Glomerulonefritis Membranosa/epidemiología , Glomerulonefritis/epidemiología , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/inmunología , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/patología , Enfermedades Autoinmunes/patología , Membrana Basal Glomerular/patología , Glomerulonefritis/inmunología , Glomerulonefritis/patología , Glomerulonefritis Membranoproliferativa/patología , Glomerulonefritis Membranosa/patología , Humanos , Glomérulos Renales/inmunología , Glomérulos Renales/patologíaRESUMEN
Anti-glomerular basement membrane (anti-GBM) antibody disease is a rare, but well characterized cause of glomerulonephritis. It is defined by the presence of autoantibodies directed at specific antigenic targets within the glomerular basement membrane. This pattern of rapidly progressive glomerulonephritis and alveolar hemorrhage is often referred to as Goodpasture's syndrome. The prognosis for patients with anti-GBM antibody disease is poor. In Japan, to improve the prognosis of patients with rapidly progressive glomerulonephritis (RPGN), we conducted a nationwide survey of patients with RPGN and investigated the initial symptoms, laboratory findings including renal biopsy findings, treatment methods, and outcomes. Among patients with RPGN, patients with anti-GBM antibody disease were rare: 6.6% (47/715). Alveolar hemorrhage (Goodpasture's syndrome) was observed in 23.4% of patients with anti-GBM antibody disease. Most patients with anti-GBM antibody disease had renal failure at the time of diagnosis. The mean serum creatinine level of patients with renal-limited anti-GBM antibody disease was 7.07 +/- 4.21 mg/dl and that of patients with Goodpasture's syndrome was 7.99 +/- 4.31 mg/dl. The mean level of crescent formation was 78.99 +/- 23.54% in patients with anti-GBM antibody disease, and a cellular crescent form was observed in 63.2% of those patients. The prognosis for patients with anti-GBM antibody disease is poor; the renal survival rate at 6 months after onset was 20.9%, and the mortality at 6 months after onset was 23.3%. To improve the prognosis for anti-GBM antibody disease, it may be necessary to detect this disease in the early stages and to treat it without delay.