Primary Membranous Nephropathy With Extremely High Levels Of Ca-125 / Nefropatía Membranosa Primaria Con Niveles Extremadamente Altos De Ca-125

Abstract Membranous nephropathy is a glomerular disease that causes nephrotic syndrome. Absent phospholipase A2 receptor antibodies and absent staining with IgG4 may be linked to malignancy-associated MN. Here we present a case that defies that suggestion. A 42-year-old female presented with anasarca. Kidney biopsy revealed membranous nephropathy, stained positive for IgG but negative for IgG4. Absent phospholipase A2 receptor antibodies was negative. Abdominal tomography revealed a partial thrombosis of the left ovarian vein which raised suspicion for ovarian cancer. Even though her ovaries did not uptake FDG on PET scan, a carbohydrate antigen-125 was ordered. She had extremely high levels of carbohydrate antigen-125 which was unexpected in the course of benign events. Thorax CT, endoscopy, colonoscopy, mammography, and positron emission tomography were clear in terms of malignancy. Samples from both pleural effusion and ascites were consistent with transudate. Tuberculosis tests were negative. Cytology samples were negative for malign cells. Exploratory surgery was planned but rejected by the patient. She was treated as primary disease with cyclosporine and methylprednisolone. Rituximab was off-limits due to insurance rules. She had prompt and excellent response. Steroids were tapered and stopped at sixth month and cyclosporine at twelfth month. In her 36 months of drug-free follow up there has been no disease recurrence or a sign of cancer. Even when all odds are towards malignancy-associated membranous nephropathy, primary disease is still a possibility. We need better markers for malignancy-associated membranous nephropathy.A very high level of CA-125 does not necessarily mean cancer.

Resumen La nefropatía membranosa es una enfermedad glomerular que causa el síndrome nefrótico. La ausencia de anticuerpos contra el receptor de fosfolipasa A2 y de tinción para IgG4 puede deberse a una nefropatía membranosa asociada a cáncer. A continuación, se presenta un caso que desafía esta sugerencia. Una paciente de 42 años realizó una consulta por anasarca. A partir de la biopsia de riñón, se diagnosticó nefropatía membranosa con tinción positiva para IgG, pero negativa para IgG4. No se detectó la presencia de anticuerpos contra el receptor de fosfolipasa A2. La tomografía abdominal reveló una trombosis parcial en la vena ovárica izquierda, lo cual generó sospecha de cáncer de ovario. Si bien los ovarios no mostraron absorción de FDG en la tomografía por emisión de positrones, se solicitó una prueba de antígeno carbohidrato 125. Se le detectaron niveles elevados del antígeno carbohidrato 125, lo cual no es esperable en casos de eventos benignos. La tomografía computarizada de tórax, endoscopía, colonoscopía, mamografía y tomografía por emisión de positrones no mostraron tumores. Las muestras de derrame pleural y de ascitis fueron indicativas de trasudado. Las pruebas de tuberculosisarrojaron resultados negativos. El examen citológico fue negativo para células malignas. Se sugirió una cirugía exploradora, pero la paciente no aceptó. Se la trató con ciclosporina y metilprednisolona por enfermedad primaria. No se utilizó rituximab por reglas de su cobertura médica. La paciente tuvo una excelente respuesta al tratamiento de forma rápida. Los esteroides se disminuyeron de forma progresiva y se suspendieron a los seis meses, y la ciclosporina, a los doce meses. Durante los 36 meses de seguimiento sin medicación no ha habido recidiva ni signos de cáncer. Incluso cuando existen grandes probabilidades de que se trate de una nefropatía membranosa asociada a cáncer, aún es posible que se trate de una enfermedad primaria. Es necesario contar con mejores marcadores de nefropatía membranosa asociada a cáncer. Un nivel elevado de CA-125 no necesariamente es indicador de cáncer.

Glomerulopatía membranosa con glomerulonefritis necrosante. Una asociación infrecuente / Membranous glomerulopathy with necrotizing glomerulonephritis. An infrequent association

Resumen Antecedentes: la asociación entre glomerulopatía membranosa y glomerulonefritis necrosante crescéntica es infrecuente: 0.4%, confiriendo un escenario de peor pronóstico. Se requieren estudios que precisen el esquema de tratamiento óptimo, sin embargo, el rápido inicio de terapia inmunosupresora impacta en la preservación de la función renal. Objetivo: exponer un caso en el cual se presenta esta asociación y tiene adecuada respuesta con el tratamiento realizado. Métodos: en este artículo se presenta un caso de una mujer con síndrome nefrótico a quien se le documenta glomerulopatía membranosa con proliferación extracapilar confirmada con biopsia renal, sin evidencia de autoinmunidad, neoplasia ni proceso infeccioso. Tras el diagnóstico se inició manejo con metilprednisolona y ciclofosfamida con adecuada evolución, sin deterioro de la función renal y con mejoría de proteinuria. Conclusión: la presencia de proliferación extracapilar da peor pronóstico en los pacientes con glomerulopatía membranosa, el inicio oportuno del tratamiento es fundamental. (Acta Med Colomb 2019; 44: 39-42).

Abstract Background: the association between membranous glomerulopathy and crescentic necrotizing glomerulonephritis is infrequent: 0.4%, conferring a worst prognosis scenario. Studies that require the optimal treatment scheme are required; however, it has been described that the rapid onset of immunosuppressive therapy impacts on the preservation of renal function. Objective: to present a case in which this association is presented and has an adequate response to the performed treatment. Methods: in this article, a case of a woman with nephrotic syndrome with a documented membranous glomerulopathy with extracapillary proliferation confirmed by renal biopsy, without evidence of autoimmunity, neoplasia or infectious process is presented. After the diagnosis, treatment with methylprednisolone and cyclophosphamide was started with adequate evolution, without deterioration of renal function and with improvement of proteinuria. Conclusion: the presence of extracapillary proliferation gives worse prognosis in patients with membranous glomerulopathy. The timely initiation of treatment is essential. (Acta Med Colomb 2019; 44: 39-42).

Glomerulopatías combinadas: comunicación de 2 casos pediátricos / Combined glomerulopathies: two pediatric cases

La combinación de glomerulopatías es infrecuente en la población pediátrica. Su presencia debe ser sospechada en aquellos pacientes con una enfermedad glomerular de curso clínico atípico. La influencia a largo plazo sobre el deterioro funcional renal permanece incierta. Se presentan dos niños con características histológicas de glomerulopatía combinada.

Combined glomerulopathy is infrequent in pediatric patients. Its presence should be suspected in those patients with glomerulophaties with atypical course. The influence on the long-term renal impairment remains uncertain. Here we report two children with histological findings of combined glomerulopathy.

Nefropatía membranosa secundaria a exposición laboral con mercurio metálico

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.

Perfil clínico-epidemiológico de glomerulopatia membranosa primária em brasileiros (71 casos) / Clinical-epidemiological profile of primary membranous glomerulopathy in Brazilian patients (71 cases)

Introdução: A glomerulopatia membranosa (GNM) é uma das causas mais comuns de síndrome nefrótica em adultos, podendo ser idiopática ousecundária. Inicialmente, a maioria dos pacientes apresenta função renal preservada. O curso clínico é variável, contemplando um espectro que vai desde a remissão espontânea da proteinúria até a progressão para insuficiência renal. Objetivo: O objetivo deste estudo foi traçar o perfil clínico-epidemiológico dos pacientes portadores de GNM primária no nosso Serviço e comparar nossos dados com o de levantamentos similares. Pacientes e Métodos: Foram avaliados, retrospectivamente, dados clínicos, epidemiológicos, laboratoriais e histopatológicos de 71 pacientes portadores de GNM primária, acompanhados no Ambulatório de Nefrites da UNIFESP-EPM, no período de 1976 a 2006. Resultados: Foram registrados 71 pacientes (43% do total)com a forma primária da doença, seguidos por pelo menos seis meses. Todos eram adultos, com idade mediana de 43 anos, predominantemente brancos e homens. Creatinina sérica e proteinúria medianas iniciais eram de, respectivamente, 1,1mg/dl e 6,4g/24h e as finais foram de 1,1mg/dl e 1,2g/24h. Hipertensão Arterial Sistêmica (HAS) e hematúria microscópica estiveram presentes em, respectivamente, 50% e 77,5% dos pacientes. A sobrevida livrede insuficiência renal em dez anos foi de 74,3%. Conclusões: No nosso serviço, as características clínicas, epidemiológicas, laboratoriais e morfológicas não diferiram, na sua grande maioria, de estudos semelhantes em todo o mundo, exceto por uma freqüência mais elevada de hematúria microscópica e HAS. Ao final de 30 anos, a probabilidade de apresentar algum grau de insuficiência renal foi de 28%.

Introduction: Membranous glomerulopathy is one of the most frequent causes of nephrotic syndrome in adults. It can be idiopathic or secondary. Initially the majority of the patients has normal renal function. The clinical course is variable, i.e., it includes since spontaneous remission of proteinuria to chronic renal failure. Objective: The aim of this study was to determine the clinical and epidemiological profile of the patients with membranous glomerulopathy of our service and to compare these results to data from similar surveys. Patients and Methods: We evaluated retrospectively clinical, epidemiological, laboratorial and histological data from 71 patients with primary membranous glomerulopathy, followed up in the Glomerulopathies Section of the NephrologyService (UNIFESP-EPM), from 1976 to 2006. Results: Considering all cases of membranous glomerulopathy, 71 (43%) had the primary form of the disease and they were followed up for at least six months. All of them were adults, predominantly white males, with median age of 43 years. The median serum creatinine and proteinuria at presentation of disease were 1.1 mg/dl and 6.4 g/24h and at the end of follow-up were 1.1 mg/dl and 1.2 g/24h, respectively. Hypertension and microscopic hematuria were seen in 50 and 75% of the patients, respectively. Renal survival was 74.3% by 10 years of follow-up. Conclusions: In our service, the clinical, epidemiological, laboratorial and morphological features of membranous glomerulopathy were not different from those of other similar studies in the world, except for a higher frequency of hypertension and microscopic hematuria. At presentation patients had normal renal function and at the end of 30 years the renal survival was 28%.