ABSTRACT
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.
ABSTRACT
Objective:To investigate the value of serum anti-PLA2 R as a diagnostic marker of idiopathic membranous nephropathy( IMN).Methods:All available articles about serum anti-PLA2 R as a marker of IMN which were published at home and abroad from 2009.1 to 2013.12 were pooled from the databases of PubMed,Elsevier,Springer,CNKI,VIP and Wanfang database et al. The quality of the papers were evaluated by the quality assessment for studies of diagnostic accuracy studies( QUADAS).And then a meta-analysis was conducted by the statistical softwares of Meta-Disc and Stata.The diagnostic value of serum anti-PLA2 R in IMN was evaluated by the statistical indicators of pooled sensitivity, pooled specificity, pooled likelihood ratio and summary receiver operating characteristic curve( ROC curve).Sensitivity analysis was performed by reducing a paper in order,and publication bias was tested by Egger funnel plot.Results: Seven articles were selected to the meta-analysis according to the inclusion criteria and 967 cases were included in the study ( 454 IMN patients and 513 controls ).Heterogeneity test showed no heterogeneity threshold effect ( Spearman correlation coefficient was 0.107,P=0.819),but there was heterogeneity caused by non threshold effects(Cochrane-Q was 16.89,P=0.009 7).So random model was used to pool the effect size.The overall combined effect sizes:sensitivity was 69%,95%CI:0.65-0.73;specificity:98%,95%CI:0.96-0.99;pooled positive likelihood ratio 16.37,95%CI:4.06-65.95;pooled negative likelihood ratio 0.32,95%CI:0.24-0.43;AUC of SROC:0.854 0,Q*=0.785 0.Sensitivity analysis showed that this research was stable and reliable and Egger funnel plot showed little publication bias.Conclusion: Serum anti-PLA2 R is an useful biomarker to the diagnosis of IMN.
ABSTRACT
Objective To discuss the relationship between serum anti-Phosphalipase A2 receptor (PLA2R) antibodies and glomerular IgG4 subclass in patients with membranous nephropathy and evaluate the diagnostic value of the two markers.Methods Patients diagnosed as membranous nephropathy from October 2011 to April 2014 in Peking Union Medical College Hospital were included and divided into IMN and SMN groups accoding to their clinical diagnosis.Serum anti-PLA2R antibodies and glomerular IgG subclasses were both detected by indirect immunofluorescence assay.Receiver operator characteristic curves were used to evaluate the diagnostic efficiency of anti-PLA2R antibodies and glomerular IgG4.Results Prevalence of serum anti-PLA2R antibodies of IMN patients was 69.5％ (41/59); prevalence of MLN patients was 4.8％ (1/21).Within the IMN group,thirty-five patients showed positive results of both serum anti-PLA2R antibodies and glomerular IgG4; Six patients were positive for serum anti-PLA2R antibodies but negative for glomerular IgG4; Seventeen patients were positive for glomerular IgG4 but negative for serum anti-PLA2R antibodies; one patient was negative for both tests.The sensitivity of serum anti-PLA2R antibody was 69.5％ and the specificity was 95.2％; the sensitivity of glomerular IgG4 was 89.8％ and the specificity was 52.3％.The sensitivity of the combined marker consisting of serum anti-PLA2R antibody and glomerular IgG4 was 59.3％ and the specificity was 100％.Four out of the six patients secondary to HBV infection,one out of the three patients secondary to Sj(o)gren syndrome,one out of the three patients secondary to malignant tumor showed positive results of serum anti-PLA2R antibodies.Conclusions Serum antiPLA2R antibodies were of high prevalence among IMN patients; the prevalence among SMN patients varied with etiologies.Results of serum anti-PLA2R antibodies and glomerular IgG4 were helpful to rule out secondary etiologies in the diagnosis of membrnous nephropathy.