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).

A Case of Crescentic Glomerulonephritis Superimposed on Membranous Glomerulopathy / 대한신장학회지

Membranous glomerulopathy (MGN) is a common cause of nephrotic syndrome in adults. Renal failure gradually develops in patients with MGN and crescentic glomerulonephritis (CGN) superimposed on MGN is a rare cause of acute renal failure. In most cases patients showed nephrotic syndrome with acute renal failure. We report a 33-year-old woman with azotemia but with no other symptoms such as nephrotic syndrome she had been diagnosed to have MGN 15 months before. There seemed to be no other cause of azotemia. Renal biopsy was performed and revealed CGN on existing MGN. She was treated with immunosuppression treatment and azotemia was improved. When unexplained azotemia develops in patients with MGN, we should promptly investigate superimposed conditions including CGN. In CGN superimposed on MN, a potentially reversible condition with appropriate immunosuppression therapy should be considered.

One Case of Chronic Renal Failure and Another Case of Membraneous Glomerulonephritis Complicated by Acute A Viral Hepatitis / 대한신장학회지

Acute A viral hepatitis is a mild, self-limiting disease of liver and acute renal failure (ARF) is a rare complication. We report two cases of chronic renal failure (CRF) in nonfulminant acute A viral hepatitis and ARF. A 40-year-old man was admitted with ARF and acute A viral hepatitis, and underwent temporary hemodialysis therapy. The renal biopsy showed acute tubular necrosis with tubulointerstitial nephritis. At 13 months after discharge serum creatinine was 1.33 mg/dL and protein-creatinine ratio of spot urine was 0.47 (mg/mg Cr). The second case was a 28-year-old man and was managed conservatively. At discharge the serum creatinine was 3.14 mg/dL and the urinalysis showed hematuria, and protein-creatinine ratio 0.56 (mg/mg Cr). Thirty-nine months after discharge, the creatinine was 1.23 mg/dL, the urinalysis showed persistent nephritis findings and the protein-creatinine ratio 1.28. Kidney biopsy revealed the membranous glomerulopathy with mild tubulointerstitial nephritis, and all of findings suggested the systemic disease-associated secondary glomerulopathy. To our knowledge our case is the first one of chronic glomerulapathy that is confirmed by kidney biopsy.

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%.

Membranous Glomerulopathy Showing Asymptomatic Isolated Microscopic Hematuria Only

PURPOSE: Membranous glomerulopathy is a glomerular disease characterized by the presence of subepithelial immune deposits with thickening of the capillary wall of the glomerulus without inflammatory change. The pathogenesis of membranous glomerulopathy is still unknown. Its incidence is higher in males, and it is rarely found in infants and adolescents. Among the clinical manifestations proteinuria is most common, while edema and hematuria are present. According to reports from other countries, among few patients diagnosed with membranous glomerulopathy by renal biopsy, show isolated microscopic hematuria without the clinical manifestations. Little research in this area has been performed in Korea, and so we conducted retrograde studies on membranous glomerulopathy associated with isolated microscopic hematuria. MATERIALS AND METHODS: We analyzed retrogradely 109 cases of asymptomatic isolated microscopic hematuria that were diagnosed as membranous glomerulopathy by renal biopsy at Yonsei University Severance hospital from January, 1992 to July, 2001. RESULTS: In 87 of the 109 cases patients were over 15 years old while in 22 cases patients were under 15 at the time of dignosis. Only three patients showed isolated microscopic hematuria without the clinical manifestations and abnormal laboratory findings and they were all male patients under 15 years old. CONCLUSION: Few cases of the membranous glomerulopathy show only asymptomatic isolated microscopic hematuria. However, since membranous glomerulopathy can be found in patients who present with asymptomatic isolated microscopic hematuria only, if adequate indication for renal biopsy is present, we conclude that renal biopsy must be aggresively pursued in order to find the underlying disease.