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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Membranous glomerulonephritis &#40;MGN&#41; is an autoimmune disease characterised by subepithelial immune complex deposits&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">1&#44;2</span></a> Approximately 75&#37; of MGN cases are primary or idiopathic&#44; with the rest being secondary forms associated with systemic diseases&#44; infections&#44; cancer and drugs&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">2</span></a> Among adult patients with primary MGN&#44; 70&#8211;80&#37; have circulating antibodies to the M-type receptor of phospholipase A2 &#40;anti-PLA2R&#41;&#44; located on the podocyte membrane&#46; Not described in other glomerular diseases&#44; these antibodies have diagnostic value for primary MGN&#44; and correlate with clinical activity and response to treatment&#46;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">3&#44;4</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">We describe a patient with MGN who had tested positive for anti-PLA2R using two techniques with a histological pattern suggesting a secondary cause&#44; probably lupus&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">This was a 77-year-old male referred for nephrotic syndrome&#46; His medical history included a 40&#8211;50-year history of epilepsy&#44; on treatment with diphenylhydantoin&#46; Eight months earlier he had begun to have lower limb oedema and raised blood pressure&#46; He reported nocturia 2&#8211;3 times a night&#44; with no other systemic symptoms&#44; and was on treatment with diphenylhydantoin&#44; amlodipine&#44; furosemide and enoxaparin&#46; Physical examination revealed&#58; blood pressure 143&#47;86<span class="elsevierStyleHsp" style=""></span>mmHg and oedema of the lower limbs with fovea to the knees&#59; the rest of the examination was unremarkable&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Laboratory tests found&#58; haemoglobin 10&#46;3<span class="elsevierStyleHsp" style=""></span>g&#47;dL&#59; leukocytes 6310&#47;mm<span class="elsevierStyleSup">3</span> &#40;lymphocytes 1300&#47;mm<span class="elsevierStyleSup">3</span>&#41;&#59; MCV and MCHC normal&#59; platelets 276&#44;000&#59; iron 82<span class="elsevierStyleHsp" style=""></span>mcg&#47;dL&#59; ferritin 29&#46;2<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&#59; direct Coombs negative&#59; urea 32<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#59; creatinine 1&#46;20<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#59; albumin 2&#46;3<span class="elsevierStyleHsp" style=""></span>g&#47;dL&#59; coagulation&#44; electrolytes and rest of clinical biochemistry trace elements were normal&#46; IgG was 461<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#44; IgM 34<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#44; and IgA normal&#46; High resolution serum protein electrophoresis&#58; weak monoclonal IgG kappa component &#40;kappa chains 52&#46;6<span class="elsevierStyleHsp" style=""></span>mg&#47;L&#44; lambda chains 27&#46;2<span class="elsevierStyleHsp" style=""></span>mg&#47;L&#44; kappa&#47;lambda ratio 1&#46;94&#41;&#46; Anti-PLA2R antibodies were positive by indirect immunofluorescence and by ELISA 274<span class="elsevierStyleHsp" style=""></span>U&#47;mL &#40;reference value &#60;20&#41;&#44; &#40;indirect immunofluorescence and ELISA&#58; Medizinische Labordiagnostika&#44; EUROINMUN AG&#44; Luebeck&#44; Germany&#41;&#46; Immunology tests&#58; ANA&#43; 1&#47;1280&#59; C3&#44; C4&#44; anti-DNA&#44; anti-histones&#44; ENA&#44; anti-cardiolipin antibodies&#44; ANCA&#44; anti-TPO and cryoglobulins normal&#47;negative&#46; Angiotensin converting enzyme&#44; thyroid hormones and PSA were normal&#46; Urine&#58; proteinuria 8&#46;920<span class="elsevierStyleHsp" style=""></span>g&#47;24<span class="elsevierStyleHsp" style=""></span>h &#40;high resolution electrophoresis&#58; non-selective glomerular pattern&#44; weak monoclonal IgG kappa component&#41;&#46; Urine culture was negative&#46; Mantoux and QuantiFERON were also negative&#46; Serology was negative for HBV&#44; HCV&#44; HIV&#44; Parvovirus B19 and CMV&#59; EBV infection in the past&#46; HBV PCR and HCV PCR were negative&#46; RPR was negative&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">No abnormalities were observed on chest X-ray or echocardiogram&#59; chest&#8211;abdomen&#8211;pelvis CT found bilateral lamellar pleural effusion&#44; with no other abnormalities&#59; MRI of renal veins found no signs of thrombosis&#59; gastro&#47;colonoscopy&#58; colon polyps detected and resected &#40;biopsy&#58; tubular adenomas with low grade dysplasia&#41;&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Percutaneous renal biopsy was performed &#40;18 glomeruli&#44; 2 of them sclerotic&#41;&#44; showing thickening of basement membranes with vacuolated appearance and mesangial proliferation&#59; immunofluorescence revealed IgG and C3 with diffuse granular pattern in the capillary walls and mesangium&#44; C1q negative&#44; kappa and lambda positive &#40;&#43;&#43;&#43;&#41;&#59; the electron microscopy study showed massive subendothelial&#44; subepithelial and mesangial deposits and podocyte fusion &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; Taken as a whole&#44; the picture was consistent with secondary MGN&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">The patient was prepared for sedated colonoscopy with senna and saline enema&#46; During the study&#44; he developed hypotension and his creatinine rose to 1&#46;69<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#46; ACE inhibitor&#47;ARA2 treatment were not used&#44; at least initially&#44; and the patient was treated with prednisone and mycophenolate mofetil&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Our first diagnostic impression was primary MGN&#46; However&#44; the presence of mesangial proliferation and subendothelial and mesangial deposits suggested a secondary form of MGN&#46; Obviously hepatitis B and C and cancer were ruled out&#46; There was no light chain restriction&#44; so it did not appear to be a monoclonal gammapathy with renal involvement&#46; We believe that our patient may have latent systemic lupus erythematosus &#40;SLE&#41;&#46; Lupus MGN can present with few clinical and serological manifestations of this disease&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">5</span></a> Nevertheless&#44; this patient could be diagnosed with SLE according to SLICC criteria&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">6</span></a> It seems unlikely that diphenylhydantoin played any role&#44; because nephropathy is rare in drug-induced lupus and anti-histone antibodies are usually positive&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Anti-PLA2R antibodies are a useful biomarker for the diagnosis of primary MGN&#59; studies have shown anti-PLA2R detection techniques to have a sensitivity of 94&#46;4&#37; &#40;indirect immunofluorescence&#41; and 97&#46;2&#37; &#40;ELISA&#41;&#44; and a specificity of 100&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">7</span></a> Positive anti-PLA2R has been described in membranous nephropathy secondary to cancer&#44; lupus&#44; hepatitis B and sarcoidosis&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">1</span></a> Qin et al&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">8</span></a> studied 20 patients with lupus membranous nephropathy&#44; one of whom was positive for anti-PLA2R&#46; Another study<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">9</span></a> included 25 patients of predominantly European origin diagnosed with lupus membranous nephropathy&#59; anti-PLA2R was not detected in any of them&#46; Anti-PLA2R positivity in lupus MGN is therefore uncommon&#44; of doubtful significance and may merely be a coincidence&#46; However&#44; in membranous nephropathy secondary to HBV and sarcoidosis with positive anti-PLA2R&#44; these antibodies may play a pathogenic role&#46;<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">10&#44;11</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">It has been suggested that a diagnosis of MGN can be assumed in nephrotic syndrome with positive anti-PLA2R&#44; especially in cases of risk for renal biopsy&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">1</span></a> As this patient illustrates&#44; unless there is a serious contraindication&#44; the biopsy provides additional information&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0055" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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Letter to the Editor
Nephrotic syndrome, anti-PLA2R and membranous glomerulonephritis. Is the renal biopsy necessary?
Síndrome nefrótico, anticuerpos anti-PLA2R y glomerulonefritis membranosa. ¿Es necesaria la biopsia renal?
Raúl Alvaradoa,
Corresponding author
raulalvarado202930@gmail.com

Corresponding author.
, Ricardo Enríqueza, Tania Mucib, Ana Esther Sirventa, Valle Lozano Verac, Isabel Millána, Cesar Gonzáleza
a Sección de Nefrología, Hospital General Universitario de Elche, Elche, Spain
b Sección de Anatomía Patológica, Hospital General Universitario de Elche, Elche, Spain
c Servicio de Análisis Clínico, Hospital General Universitario de Elche, Elche, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Membranous glomerulonephritis &#40;MGN&#41; is an autoimmune disease characterised by subepithelial immune complex deposits&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">1&#44;2</span></a> Approximately 75&#37; of MGN cases are primary or idiopathic&#44; with the rest being secondary forms associated with systemic diseases&#44; infections&#44; cancer and drugs&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">2</span></a> Among adult patients with primary MGN&#44; 70&#8211;80&#37; have circulating antibodies to the M-type receptor of phospholipase A2 &#40;anti-PLA2R&#41;&#44; located on the podocyte membrane&#46; Not described in other glomerular diseases&#44; these antibodies have diagnostic value for primary MGN&#44; and correlate with clinical activity and response to treatment&#46;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">3&#44;4</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">We describe a patient with MGN who had tested positive for anti-PLA2R using two techniques with a histological pattern suggesting a secondary cause&#44; probably lupus&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">This was a 77-year-old male referred for nephrotic syndrome&#46; His medical history included a 40&#8211;50-year history of epilepsy&#44; on treatment with diphenylhydantoin&#46; Eight months earlier he had begun to have lower limb oedema and raised blood pressure&#46; He reported nocturia 2&#8211;3 times a night&#44; with no other systemic symptoms&#44; and was on treatment with diphenylhydantoin&#44; amlodipine&#44; furosemide and enoxaparin&#46; Physical examination revealed&#58; blood pressure 143&#47;86<span class="elsevierStyleHsp" style=""></span>mmHg and oedema of the lower limbs with fovea to the knees&#59; the rest of the examination was unremarkable&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Laboratory tests found&#58; haemoglobin 10&#46;3<span class="elsevierStyleHsp" style=""></span>g&#47;dL&#59; leukocytes 6310&#47;mm<span class="elsevierStyleSup">3</span> &#40;lymphocytes 1300&#47;mm<span class="elsevierStyleSup">3</span>&#41;&#59; MCV and MCHC normal&#59; platelets 276&#44;000&#59; iron 82<span class="elsevierStyleHsp" style=""></span>mcg&#47;dL&#59; ferritin 29&#46;2<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&#59; direct Coombs negative&#59; urea 32<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#59; creatinine 1&#46;20<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#59; albumin 2&#46;3<span class="elsevierStyleHsp" style=""></span>g&#47;dL&#59; coagulation&#44; electrolytes and rest of clinical biochemistry trace elements were normal&#46; IgG was 461<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#44; IgM 34<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#44; and IgA normal&#46; High resolution serum protein electrophoresis&#58; weak monoclonal IgG kappa component &#40;kappa chains 52&#46;6<span class="elsevierStyleHsp" style=""></span>mg&#47;L&#44; lambda chains 27&#46;2<span class="elsevierStyleHsp" style=""></span>mg&#47;L&#44; kappa&#47;lambda ratio 1&#46;94&#41;&#46; Anti-PLA2R antibodies were positive by indirect immunofluorescence and by ELISA 274<span class="elsevierStyleHsp" style=""></span>U&#47;mL &#40;reference value &#60;20&#41;&#44; &#40;indirect immunofluorescence and ELISA&#58; Medizinische Labordiagnostika&#44; EUROINMUN AG&#44; Luebeck&#44; Germany&#41;&#46; Immunology tests&#58; ANA&#43; 1&#47;1280&#59; C3&#44; C4&#44; anti-DNA&#44; anti-histones&#44; ENA&#44; anti-cardiolipin antibodies&#44; ANCA&#44; anti-TPO and cryoglobulins normal&#47;negative&#46; Angiotensin converting enzyme&#44; thyroid hormones and PSA were normal&#46; Urine&#58; proteinuria 8&#46;920<span class="elsevierStyleHsp" style=""></span>g&#47;24<span class="elsevierStyleHsp" style=""></span>h &#40;high resolution electrophoresis&#58; non-selective glomerular pattern&#44; weak monoclonal IgG kappa component&#41;&#46; Urine culture was negative&#46; Mantoux and QuantiFERON were also negative&#46; Serology was negative for HBV&#44; HCV&#44; HIV&#44; Parvovirus B19 and CMV&#59; EBV infection in the past&#46; HBV PCR and HCV PCR were negative&#46; RPR was negative&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">No abnormalities were observed on chest X-ray or echocardiogram&#59; chest&#8211;abdomen&#8211;pelvis CT found bilateral lamellar pleural effusion&#44; with no other abnormalities&#59; MRI of renal veins found no signs of thrombosis&#59; gastro&#47;colonoscopy&#58; colon polyps detected and resected &#40;biopsy&#58; tubular adenomas with low grade dysplasia&#41;&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Percutaneous renal biopsy was performed &#40;18 glomeruli&#44; 2 of them sclerotic&#41;&#44; showing thickening of basement membranes with vacuolated appearance and mesangial proliferation&#59; immunofluorescence revealed IgG and C3 with diffuse granular pattern in the capillary walls and mesangium&#44; C1q negative&#44; kappa and lambda positive &#40;&#43;&#43;&#43;&#41;&#59; the electron microscopy study showed massive subendothelial&#44; subepithelial and mesangial deposits and podocyte fusion &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; Taken as a whole&#44; the picture was consistent with secondary MGN&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">The patient was prepared for sedated colonoscopy with senna and saline enema&#46; During the study&#44; he developed hypotension and his creatinine rose to 1&#46;69<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#46; ACE inhibitor&#47;ARA2 treatment were not used&#44; at least initially&#44; and the patient was treated with prednisone and mycophenolate mofetil&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Our first diagnostic impression was primary MGN&#46; However&#44; the presence of mesangial proliferation and subendothelial and mesangial deposits suggested a secondary form of MGN&#46; Obviously hepatitis B and C and cancer were ruled out&#46; There was no light chain restriction&#44; so it did not appear to be a monoclonal gammapathy with renal involvement&#46; We believe that our patient may have latent systemic lupus erythematosus &#40;SLE&#41;&#46; Lupus MGN can present with few clinical and serological manifestations of this disease&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">5</span></a> Nevertheless&#44; this patient could be diagnosed with SLE according to SLICC criteria&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">6</span></a> It seems unlikely that diphenylhydantoin played any role&#44; because nephropathy is rare in drug-induced lupus and anti-histone antibodies are usually positive&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Anti-PLA2R antibodies are a useful biomarker for the diagnosis of primary MGN&#59; studies have shown anti-PLA2R detection techniques to have a sensitivity of 94&#46;4&#37; &#40;indirect immunofluorescence&#41; and 97&#46;2&#37; &#40;ELISA&#41;&#44; and a specificity of 100&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">7</span></a> Positive anti-PLA2R has been described in membranous nephropathy secondary to cancer&#44; lupus&#44; hepatitis B and sarcoidosis&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">1</span></a> Qin et al&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">8</span></a> studied 20 patients with lupus membranous nephropathy&#44; one of whom was positive for anti-PLA2R&#46; Another study<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">9</span></a> included 25 patients of predominantly European origin diagnosed with lupus membranous nephropathy&#59; anti-PLA2R was not detected in any of them&#46; Anti-PLA2R positivity in lupus MGN is therefore uncommon&#44; of doubtful significance and may merely be a coincidence&#46; However&#44; in membranous nephropathy secondary to HBV and sarcoidosis with positive anti-PLA2R&#44; these antibodies may play a pathogenic role&#46;<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">10&#44;11</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">It has been suggested that a diagnosis of MGN can be assumed in nephrotic syndrome with positive anti-PLA2R&#44; especially in cases of risk for renal biopsy&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">1</span></a> As this patient illustrates&#44; unless there is a serious contraindication&#44; the biopsy provides additional information&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0055" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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