RESUMO
Membranous nephropathy is a glomerulopathy, which main affected target is the podocyte, and has consequences on the glomerular basement membrane. It is more common in adults, especially over 50 years of age. The clinical presentation is nephrotic syndrome, but many cases can evolve with asymptomatic non-nephrotic proteinuria. The mechanism consists of the deposition of immune complexes in the subepithelial space of the glomerular capillary loop with subsequent activation of the complement system. Great advances in the identification of potential target antigens have occurred in the last twenty years, and the main one is the protein "M-type phospholipase-A2 receptor" (PLA2R) with the circulating anti-PLA2R antibody, which makes it possible to evaluate the activity and prognosis of this nephropathy. This route of injury corresponds to approximately 70% to 80% of cases of membranous nephropathy characterized as primary. In the last 10 years, several other potential target antigens have been identified. This review proposes to present clinical, etiopathogenic and therapeutic aspects of membranous nephropathy in a didactic manner, including cases that occur during kidney transplantation.
Assuntos
Glomerulonefrite Membranosa , Síndrome Nefrótica , Adulto , Humanos , Pessoa de Meia-Idade , Glomerulonefrite Membranosa/diagnóstico , Glomerulonefrite Membranosa/etiologia , Glomerulonefrite Membranosa/terapia , Autoanticorpos/uso terapêutico , Glomérulos Renais/patologia , Prognóstico , Síndrome Nefrótica/diagnóstico , Síndrome Nefrótica/etiologia , Síndrome Nefrótica/terapiaRESUMO
Membranous nephropathy (MN) is a form of kidney disease that is idiopathic in 70%-80% of cases. Glomerular involvement in autoimmune thyroiditis can occur in 10%-30% of patients, and MN manifests in association with Hashimoto thyroiditis in up to 20% of the cases with glomerular involvement. Reports of MN associated with Graves' disease (GD) are extremely rare in the current literature. Herein, we report the case of a 46-year-old man admitted to the hospital with nephrotic syndrome and symptomatic hyperthyroidism due to GD. Kidney biopsy revealed a secondary MN pattern. Immunohistochemical staining for PLA2R was negative, and thyroglobulin showed weak and segmental staining along the glomerular capillary. Anti-thyroid peroxidase (TPO) antibody test was not performed. The patient was treated for GD with methimazole and prednisone, and despite reaching clinical improvement after 8 months, proteinuria remained close to nephrotic levels. In this scenario, the patient was submitted to radioactive iodine, and there was a dramatic reduction in proteinuria levels after treatment. In conclusion, GD association with MN is rare, and when present, diagnosis using PLA2R and immunohistochemistry can be useful in determining association. In addition, radioactive iodine therapy can be an effective treatment modality when preceded with immunosuppressive corticosteroid therapy.
Assuntos
Glomerulonefrite Membranosa , Doença de Graves , Neoplasias da Glândula Tireoide , Glomerulonefrite Membranosa/diagnóstico , Glomerulonefrite Membranosa/tratamento farmacológico , Glomerulonefrite Membranosa/etiologia , Doença de Graves/complicações , Doença de Graves/diagnóstico , Doença de Graves/tratamento farmacológico , Humanos , Radioisótopos do Iodo/uso terapêutico , Masculino , Pessoa de Meia-Idade , ProteinúriaRESUMO
ABSTRACT Idiopathic membranous nephropathy (IMN) is a frequent cause of nephrotic syndrome in adults. In terms of etiology, the condition may be categorized as primary/idiopathic or secondary. Literature on the pathophysiology of IMN has indicated the presence of autoantibodies (PLA2R and THSD7A) directed against podocyte antigens. The detection of antibodies against a domain favors IMN. The presence of autoantibodies against one of the domains would in theory exclude the possibility of there being autoantibodies against the other domain. However, cases of patients with PLA2R- and THSD7A-positive disease have been recently reported, showing that antibodies against two targets may be concomitantly produced via yet unknown pathophysiological mechanisms. This study reports the case of a 46-year-old male patient with nephrotic-range proteinuria, hematuria, hypoalbuminemia, and hypercholesterolemia submitted to biopsy and histopathology examination (LM, IF, IHC, and EM) eventually diagnosed with PLA2R- and THSD7A-positive IMN associated with IgA nephropathy, stressing our experience with the use of IgG subclasses, PLA2R, and THSD7A in the workup for MN and the relevance of adopting a broad and adequate approach to elucidating and acquiring knowledge of the pathophysiology of IMN.
RESUMO A Nefropatia Membranosa Idiopática (NMi) é uma frequente causa de síndrome nefrótica em adultos e sua etiologia pode ser estratificada em primária/idiopática ou secundária. O conhecimento da fisiopatologia da NMi sugeriu a presença de autoanticorpos (PLA2R e a THSD7A) direcionados contra antígenos existentes nos podócitos. A detecção de anticorpos contra um domínio favorece NMi. A presença de autoanticorpos contra um desses domínios autoexcluiria a possibilidade de autoanticorpos contra o outro domínio; no entanto, recentemente foram descritos casos que apresentaram dupla positividade para PLA2R e THSD7A, comprovando que, por mecanismos fisiopatológicos ainda não conhecidos, raramente pode existir produção concomitante de anticorpos contra os dois alvos. O presente estudo tem por objetivo relatar o caso de um paciente de 46 anos de idade, do sexo masculino, que apresentou quadro de proteinúria nefrótica, hematúria, hipoalbuminemia e hipercolesterolemia submetido a biópsia e exame histopatológico (ML, IF, IHQ e ME), confirmando um caso raro de NMi com positividade dupla para os anticorpos anti-PLA2R e anti-THSD7A e associação à nefropatia por IgA, mostrando nossa experiência com a utilização de subclasses de IgG, PLA2R e THSD7A na rotina laboratorial para a investigação da GNM e enfatizando a importância de uma abordagem ampla para adequada elucidação e conhecimento dos mecanismos fisiopatológicos na NMi.
Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Glomerulonefrite Membranosa/imunologia , Trombospondinas/imunologia , Receptores da Fosfolipase A2/imunologia , Biópsia , Glomerulonefrite Membranosa/diagnóstico , Glomerulonefrite Membranosa/etiologia , Glomerulonefrite Membranosa/patologia , Glomérulos Renais/patologiaRESUMO
Idiopathic membranous nephropathy (IMN) is a frequent cause of nephrotic syndrome in adults. In terms of etiology, the condition may be categorized as primary/idiopathic or secondary. Literature on the pathophysiology of IMN has indicated the presence of autoantibodies (PLA2R and THSD7A) directed against podocyte antigens. The detection of antibodies against a domain favors IMN. The presence of autoantibodies against one of the domains would in theory exclude the possibility of there being autoantibodies against the other domain. However, cases of patients with PLA2R- and THSD7A-positive disease have been recently reported, showing that antibodies against two targets may be concomitantly produced via yet unknown pathophysiological mechanisms. This study reports the case of a 46-year-old male patient with nephrotic-range proteinuria, hematuria, hypoalbuminemia, and hypercholesterolemia submitted to biopsy and histopathology examination (LM, IF, IHC, and EM) eventually diagnosed with PLA2R- and THSD7A-positive IMN associated with IgA nephropathy, stressing our experience with the use of IgG subclasses, PLA2R, and THSD7A in the workup for MN and the relevance of adopting a broad and adequate approach to elucidating and acquiring knowledge of the pathophysiology of IMN.
Assuntos
Glomerulonefrite Membranosa/imunologia , Receptores da Fosfolipase A2/imunologia , Trombospondinas/imunologia , Biópsia , Glomerulonefrite Membranosa/diagnóstico , Glomerulonefrite Membranosa/etiologia , Glomerulonefrite Membranosa/patologia , Humanos , Glomérulos Renais/patologia , Masculino , Pessoa de Meia-IdadeAssuntos
Membrana Basal Glomerular/patologia , Glomerulonefrite Membranosa/imunologia , Interações Hospedeiro-Parasita/imunologia , Schistosoma mansoni/imunologia , Esquistossomose mansoni/complicações , Adulto , Animais , Brasil , Doença Crônica , Feminino , Membrana Basal Glomerular/imunologia , Glomerulonefrite Membranosa/diagnóstico , Glomerulonefrite Membranosa/etiologia , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Schistosoma mansoni/isolamento & purificação , Esquistossomose mansoni/imunologia , Esquistossomose mansoni/parasitologiaRESUMO
Toxic nephrophaties secondary to occupational exposure to metals have been widely studied, including membranous nephropathy by mercury, which is rare. Occupational poisoning by mercury is frequent, neurological symptoms are the main form of clinical presentation. Secondary renal involvement in chronic exposure to metallic mercury can cause glomerular disease by deposit of immune-complexes. Membranous glomerulopathy and minimal change disease are the most frequently reported forms. Here we describe the case of a patient with occupational exposure to metallic mercury, where nephrotic syndrome due to membranous glomerulonephritis responded favorably to both chelation and immunosuppressive therapy.
Assuntos
Glomerulonefrite Membranosa/etiologia , Mercúrio/toxicidade , Exposição Ocupacional/efeitos adversos , Adulto , Terapia por Quelação , Glomerulonefrite Membranosa/terapia , Humanos , Imunossupressores/uso terapêutico , Masculino , Síndrome Nefrótica/etiologia , Síndrome Nefrótica/terapiaRESUMO
Las nefropatías tóxicas secundarias a la exposición ocupacional a metales han sido ampliamente estudiadas. La nefropatía membranosa por mercurio es poco frecuente.La intoxicación ocupacional con mercurio sí es frecuente, siendo las principales formas de presentación las manifestaciones clínicas neurológicas. La afectación renal secundaria a la exposición crónica a mercurio metálico puede desarrollar enfermedad glomerular por depósito de inmunocomplejos. La glomerulopatía membranosa y a cambios mínimos son las más frecuentemente comunicadas.Se presenta el caso de un paciente con exposición ocupacional a mercurio metálico, con síndrome nefrótico y biopsia renal con glomerulopatía membranosa que presentó respuesta favorable luego del tratamiento quelante e inmunosupresor.
Toxic nephrophaties secondary to occupational exposure to metals have been widely studied, including membranous nephropathy by mercury, which is rare. Occupational poisoning by mercury is frequent, neurological symptoms are the main form of clinical presentation. Secondary renal involvement in chronic exposure to metallic mercury can cause glomerular disease by deposit of immune-complexes. Membranous glomerulopathy and minimal change disease are the most frequently reported forms. Here we describe the case of a patient with occupational exposure to metallic mercury, where nephrotic syndrome due to membranous glomerulonephritis responded favorably to both chelation and immunosuppressive therapy.
Assuntos
Adulto , Humanos , Masculino , Glomerulonefrite Membranosa/etiologia , Mercúrio/toxicidade , Exposição Ocupacional/efeitos adversos , Terapia por Quelação , Glomerulonefrite Membranosa/terapia , Imunossupressores/uso terapêutico , Síndrome Nefrótica/etiologia , Síndrome Nefrótica/terapiaRESUMO
Proteinuria is a major feature of lupus nephritis (LN) and reflects podocyte injury. Analysis of podocyte biomarkers was performed attempting to identify if podocyte phenotype is distinct in pure membranous and proliferative LN. Expression of synaptopodin, Wilms tumor protein 1 (WT1), glomerular epithelial protein 1 (GLEPP1) and nephrin was evaluated in 52 LN biopsies by immunohistochemistry. Preserved synaptopodin expression was observed in only 10 (19.2%) of all biopsies while 42 (80.8%) had reduced expression. Both groups had comparable proteinuria at the time of biopsy (p = 0.22); however, in the mean follow-up of four years there was a tendency toward lower mean levels of proteinuria in patients with preserved synaptopodin staining (0.26±0.23 vs. 0.84±0.90 g/24 h, p = 0.05) compared with those with diminished expression. Thirty-nine (75%) biopsies were classified as proliferative and 13 (25%) as pure membranous. Comparison of podocyte biomarkers demonstrated a predominance of preserved staining of synaptopodin (69.2%), WT1 (69.2%), GLEPP1 (53.9%) and nephrin (60%) in the pure membranous group whereas only <10% of the proliferative showed preserved expression. Our data suggest that in proliferative forms there seems to occur structural podocyte damage, whereas in the pure membranous the predominant preserved pattern suggests a dysfunctional podocyte lesion that may account for the better long-term prognosis of proteinuria outcome.