Nefritis como debut lúpico en el embarazo: reporte de dos casos y revisión de la literatura / Nephritis as a lupic debut in pregnancy: report of two cases and review of the literature

ANTECEDENTES: El lupus eritematoso sistémico es una enfermedad autoinmunitaria multisistémica que afecta principalmente a mujeres en edad fértil. La nefritis lúpica es la manifestación clínica más frecuente durante la gestación y constituye un factor de riesgo para la pérdida del embarazo, en especial en pacientes con insuficiencia renal. Además, presenta mayor riesgo de pérdida fetal, restricción del crecimiento intrauterino e hipertensión. CASOS CLÍNICOS: El primer caso se trata de una gestante de 28 + 2 semanas con daño renal grave y anticuerpos anti-DNA en título elevado. En el segundo caso destaca el debut con sintomatología de dificultad respiratoria y edemas como manifestaciones clínicas de nefropatía lúpica tipo V a las 23 semanas de gestación. En ambas pacientes destaca la prematuridad como complicación perinatal, así como el crecimiento intrauterino retardado en el primer caso. Por último, se describen los resultados clínico-analíticos tras el inicio terapéutico específico en ambos casos. CONCLUSIONES: El diagnóstico diferencial del debut de nefritis lúpica durante la gestación continúa siendo un desafío, a pesar de los avances en cuanto a marcadores angiogénicos. La valoración clínica continúa siendo la piedra angular de este proceso diagnóstico y de sus implicaciones en cuanto a complicaciones del embarazo actuales y futuras.

BACKGROUND: Systemic lupus erythematosus is a multisystem autoimmune disease that mainly affects women of childbearing age. Lupus nephritis represents the most frequent clinical manifestation in pregnancy, constituting a risk factor for pregnancy loss, especially in patients with kidney damage. It also has a higher risk of fetal loss, intrauterine growth restriction, and gestational hypertension. CLINICAL CASES: The first case is a 28 + 2-week pregnant woman with severe kidney damage and high-titles anti-DNA antibodies. In the second case, we highlight the debut with symptoms of respiratory distress and edema as clinical manifestations of type V lupus nephropathy in a 23-week gestation. In both cases, prematurity stands out as a perinatal complication, as well as delayed intrauterine growth in the former. Finally, the clinical-analytical results are described, after the specific therapeutic initiation in both cases. CONCLUSIONS: The differential diagnosis of the onset of lupus nephritis during pregnancy continues to be a challenge, despite the advances in angiogenic markers; clinical assessment continues to be the cornerstone of this diagnostic process and its implications for current and future pregnancy complications.

Non-lupus full-house nephropathy: a case series / Nefropatia "full-house" não relacionada ao lúpus: uma série de casos

Abstract Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune inflammatory disease. However, some patients may exhibit a histological pattern of kidney injury, with characteristics indistinguishable from lupus nephritis, but without presenting any extrarenal symptoms or serologies suggestive of SLE. Such involvement has recently been called non-lupus full-house nephropathy. The objective is to report a series of clinical cases referred to the Laboratory of the Federal University of Maranhão that received the diagnosis of "full-house" nephropathy unrelated to lupus, upon immunofluorescence and to discuss its evolution and outcomes. Non-lupus full-house nephropathy represents a diagnostic and therapeutic challenge, because it is a new entity, which still needs further studies and may be the initial manifestation of SLE, isolated manifestation of SLE or a new pathology unrelated to SLE.

Resumo O lúpus eritematoso sistêmico (LES) é uma doença inflamatória crônica autoimune multissistêmica. Alguns pacientes, contudo, podem exibir um padrão histológico de lesão renal, com características indistinguíveis da nefrite lúpica, porém sem apresentar quaisquer sintomas extrarrenais ou sorologias sugestivas de LES. Tal acometimento tem sido recentemente denominado nefropatia "full-house" não relacionada ao lúpus. O objetivo é relatar uma série de casos clínicos encaminhados ao Laboratório da Universidade Federal do Maranhão que receberam o diagnóstico de nefropatia "full-house" não relacionada ao lúpus à imunofluorescência e discutir sua evolução e desfechos. A nefropatia "full-house" não relacionada ao lúpus representa um desafio diagnóstico e terapêutico por ser uma entidade nova, que ainda necessita de maiores estudos e pode ser a manifestação inicial do LES, manifestação isolada do LES ou uma patologia nova não relacionada ao LES.

Mast cells in the kidney biopsies of pediatric patients with lupus nephritis / Mastócitos em biópsias renais de pacientes pediátricos com nefrite lúpica

ABSTRACT Introduction: Mast cells may be involved in inflammation and contribute to the onset of fibrosis in lupus nephritis (LN). Objective: This study aimed to correlate the presence of mast cells in kidney biopsy specimens of pediatric patients with LN with activity (AI) and chronicity (CI) indices and assess how effectively mast cells may be used as a prognostic factor. Method: The study included 40 patients aged 6-18 years diagnosed with LN at the Renal Disease Service of the Federal University of Triângulo Mineiro between 1996 and 2015. Workup and epidemiological data were evaluated vis-à-vis AI, CI, and mast cell counts (MCC). Results: Significant positive correlations were found between mast cell counts (MCC) and AI (p = 0.003; r: 0.66) and MCC and CI (p = 0.048; r: 0.48). The ROC curve showed that mast cells were highly sensitive and specific in the differentiation of patients with an AI > 12 from individuals with an AI ≤ 12. Serum creatinine levels were higher in individuals with class IV LN than in patients with class V disease [1.50 (0.40-20.90) vs. 0.70 (0.62-0.90), p = 0.04]. Blood urea nitrogen had a positive significant correlation with MCC (p = 0.002; r: 0.75). A trend toward a negative correlation was observed between MCC and serum albumin (p = 0.06; r: -0.5459). Kidney biopsies of patients with nephrotic syndrome had higher MCC [2.12 (0.41-5.140) vs. 0.53 (0.0-3.94), p = 0.07]. Conclusion: Inflammatory cell infiltration and morphological differences between cell types in the inflammatory infiltrate are relevant factors in the assessment of the LN. Mast cell analysis and AI/CI assessment may be relevant prognostic indicators for pediatric patients with LN.

RESUMO Introdução: Mastócitos podem participar da inflamação e contribuir para fibrose na nefrite lúpica (NL). Objetivo: Correlacionar mastócitos em biópsias renais (BR) de pacientes pediátricos com NL com índices de atividade (IA) e cronicidade (IC), avaliando sua efetividade como fator prognóstico. Metodologia: Foram estudados 40 pacientes, entre 6 e 18 anos, diagnosticados com NL pelo Serviço de Nefropatologia da UFTM entre 1996 e 2015. Dados laboratoriais e epidemiológicos foram correlacionados com IA, IC e contagem de mastócitos (CM). Resultados: Encontramos correlação positiva e significativa entre contagem de mastócitos (CM) e IA (p = 0,003; r: 0,66) e entre CM e IC (p = 0,048; r: 0,48). Conforme a curva Roc, os mastócitos têm alta sensibilidade e especificidade na diferenciação de pacientes com IA menor ou maior do que 12. A creatinina sérica foi mais elevada na classe IV em relação à classe V [1,50 (0,40 - 20,90) versus 0,70 (0,62 - 0,90), p = 0,04]. Ureia sérica apresentou correlação positiva e significativa com CM (p = 0,002; r: 0,75). Observou-se tendência à correlação negativa entre CM e albumina sérica (p = 0,06; r: -0,5459). BR de pacientes com síndrome nefrótica apresentaram maior CM [2,12 (0,41 - 5,140) versus 0,53 (0,0 - 3,94), p = 0,07]. Conclusão: Não apenas o infiltrado inflamatório como também a diferenciação morfológica dos tipos celulares que o constituem são importantes para a avaliação da NL. Isso indica que a análise dos mastócitos, juntamente com a dos IA e IC, pode ajudar os nefrologistas a definirem o prognóstico de pacientes pediátricos.

Circulating exosomal micrornas as biomarkers of systemic lupus erythematosus

OBJECTIVES: Many studies indicate that microRNAs (miRNAs) could be potential biomarkers for various diseases. The purpose of this study was to investigate the clinical value of serum exosomal miRNAs in systemic lupus erythematosus (SLE). METHODS: Serum exosomes were isolated from 38 patients with SLE and 18 healthy controls (HCs). The expression of miR-21, miR-146a and miR-155 within exosomes was examined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Using receiver operating characteristic (ROC) curves, we evaluated the diagnostic value of exosomal miRNAs. RESULTS: Exosomal miR-21 and miR-155 were upregulated (p<0.01), whereas miR-146a expression (p<0.05) was downregulated in patients with SLE, compared to that in HCs. The expression of miR-21 (p<0.01) and miR-155 (p<0.05) was higher in SLE patients with lupus nephritis (LN) than in those without LN (non-LN). The analysis of ROC curves revealed that the expression of miR-21 and miR-155 showed a potential diagnostic value for LN. Furthermore, miR-21 (R=0.44, p<0.05) and miR-155 (R=0.33, p<0.05) were positively correlated with proteinuria. The expression of miR-21 was negatively associated with anti-SSA/Ro antibodies (R=−0.38, p<0.05), and that of miR-146a was negatively associated with anti-dsDNA antibodies (R=−0.39, p<0.05). CONCLUSIONS: These findings suggested that exosomal miR-21 and miR-155 expression levels may serve as potential biomarkers for the diagnosis of SLE and LN.

Pediatric lupus nephritis / Nefrite lúpica em pediatria

Abstract Involvement of the kidneys by lupus nephritis (LN) is one of the most severe clinical manifestations seen in individuals with systemic lupus erythematosus (SLE). LN is more frequent and severe in pediatric patients and has been associated with higher morbidity and mortality rates. This narrative review aimed to describe the general aspects of LN and its particularities when affecting children and adolescents, while focusing on the disease's etiopathogenesis, clinical manifestations, renal tissue alterations, and treatment options.

Resumo A nefrite lúpica (NL) é caracterizada pelo acometimento dos rins no contexto das diversas manifestações clínicas do Lupus Eritematoso Sistêmico (LES), e representa uma das manifestações clínicas mais graves da doença. A NL é mais frequente e mais grave nos pacientes pediátricos, em comparação com os adultos, e causa maiores taxas de morbidade e mortalidade. O objetivo desta revisão narrativa foi descrever os aspectos gerais da NL e suas particularidades em crianças e adolescentes, com foco em sua etiopatogênese, nas manifestações clínicas, nas alterações histopatológicas renais e na abordagem terapêutica.

Cut-off values of immunological tests to identify patients at high risk of severe lupus nephritis

Cut-off values for anti-dsDNA, anti-nucleosome and anti-C1q antibodies tests and for complement-mediated hemolytic activity (CH50) were explored to identify patients with high risk of developing severe lupus nephritis (LN). Forty-one patients with confirmed systemic lupus erythematosus (SLE) were identified; their levels for the three antibodies and complement had been measured on a same serum sample. These patients were classified based on the presence of renal involvem ent; sixteen had active proliferative LN. With the cut-off values accepted in the laboratory for SLE diagnosis (anti-dsDNA > 100 UI/ml, anti-nucleosome > 50 U/ ml or CH50 < 190 UCH50%) no significant differences were found between patients with and without LN. Anti-C1q > 40 U/ml showed a statistically significant association with LN and had 80% of specificity. Cut-off values for LN identified by Receiver Operating Characteristic curves (ROC) were higher for anti-dsDNA (> 455 IU/ml) and anti-nucleosome (>107 U/ml), lower for CH50 (< 150 UCH50%) and, for anti-C1q (> 41 U/ml) coincided with the cut-off values accepted for SLE. Anti-C1q > 134 U/ml had a 92% of specificity, 56% of sensibility and was associated with a fifteen-fold increased risk of LN. The simultaneous presence of anti-nucleosome > 107 U/ml and anti-C1q > 134 U/ml was associated with a 27-fold higher probability for LN. According to these results, the cut-off values used to detect SLE activity could be inadequate to identify patients at high risk of severe LN.

Se exploraron valores de corte para los ensayos de anti-ADNdc, anti-nucleosoma, anti-C1q y complemento hemolítico total (CH50) capaces de identificar los casos con mayor riesgo de nefritis lúpica (NL) grave. Se seleccionaron 41 pacientes ≥ 16 años con lupus eritematoso sistémico (LES) confirmado que tenían titulados los niveles de los tres anticuerpos y CH50, en una misma muestra de suero. Fueron clasificados según presencia de compromiso renal; 16 presentaron formas proliferativas de NL activa. Con los valores de corte aceptados por el laboratorio para el diagnóstico de LES (anti-ADNdc > 100 UI/ml, anti-nucleosoma > 50 U/ml o un CH50 < 190 UCH50%) no se encontraron diferencias significativas entre casos con y sin NL. Un anti-C1q > 40 U/ml tuvo una especificidad del 80% y mostró una asociación estadísticamente significativa con NL. Al aplicar curvas Receiver Operating Characteristic (ROC) para NL, se identificaron valores de corte más altos para anti-ADNdc (> 455 IU/ml) y anti-nucleosoma (> 107 U/ml), más bajo para CH50 (< 150 UCH50%) y para el anti-C1q (> 41 U/ml) coincidió con el aceptado para diagnóstico de LES. Un anti-C1q > 134 U/ml presentó una sensibilidad del 56%, una especificidad del 92% y se asoció con quince veces más riesgo de NL. La presencia simultánea de anti-C1q > 134 U/ml y anti-nucleosoma > 107 U/ml se asoció 27 veces más riesgo de NL. De acuerdo a estos resultados los valores de corte empleados para actividad en pacientes con LES podrían resultar inadecuados para identificar pacientes con mayor riesgo de NL grave.

Podocitopatía lúpica / Lupus podocytopathy

El lupus eritematoso sistémico (LES) es una enfermedad sistémica autoinmune que puede afectar a múltiples órganos. Aproximadamente el 50% de los pacientes con LES desarrollan enfermedad renal clínicamente evidente, la cual es una causa importante de morbimortalidad. El síndrome nefrótico (SN) es frecuente en los pacientes con nefritis lúpica (NL) y usualmente se asocia a depósitos de complejos inmunes en las paredes capilares, acompañados de proliferación endocapilar y necrosis. No obstante, existe un número creciente de casos reportados de pacientes con LES y SN cuyas biopsias se caracterizan por injuria podocitaria, consistente en fusión pedicelar en la microscopía electrónica y un patrón morfológico idéntico a la enfermedad por cambios mínimos (ECM), a la esclerosis focal y segmentaria primaria o a una glomerulonefritis proliferativa mesangial, en ausencia de depósitos inmunes en las paredes capilares. Este hallazgo podría deberse a la coexistencia de NL y ECM, sin embargo, la mayoría de las investigaciones consideran que esto no es una mera coincidencia. De allí surge una nueva entidad, la "podocitopatía lúpica", patología posiblemente mediada por la activación de células T y la presencia de un factor de permeación glomerular. Esto permite diferenciar al grupo de pacientes con LES y SN, que en la biopsia carecen de depósitos inmunes en las paredes capilares o de signos de actividad lúpica renal, se evidencia fusión pedicelar difusa en la ME y presentan además una alta sensibilidad al tratamiento con corticoides. El diagnóstico de esta nueva entidad, requiere de la interpretación de los hallazgos histopatológicos con la correcta integración de los datos de la inmunofluorescencia y la microscopía electrónica

Lupus Erythematosus (SLE) is a systemic autoimmune disease which may affect several organs. Approximately 50% of SLE patients develop clinically overt renal disease, an important cause of morbidity and mortality. Nephrotic syndrome (NS) is frequent in patients suffering from lupus nephritis (LN) and it is usually associated with immune complex deposition on capillary walls accompanied by endocapillary proliferation and necrosis. However, a growing number of reported cases of SLE and NS patients show biopsies which reveal podocyte injury, consisting of pedicel fusion upon electron microscopy and a morphological pattern identical to minimal change disease (MCD), primary focal segmental glomerulosclerosis or mesangial proliferative glomerulonephritis, in absence of immune complex deposition on capillary walls. Although this finding could be explained by the coexistence of LN and MCD, most researchers consider that this fact is not pure coincidence. A new term, lupus podocytopathy, therefore appears to define a distinct entity characterized by T cell activation and the presence of a glomerular permeability factor. This allows to distinguish the group of SLE and NS patients whose biopsies do not show immune complex deposition on capillary walls or signs of renal lupus activity; electron microscopy reveals diffuse pedicel fusion and patients show high responsiveness to corticosteroid treatment. In order to diagnose this new entity, it is necessary to interpret histopathological findings together with data gathered from immunofluorescence and electron microscopy

Características sociodemográficas y clínicas de pacientes con nefritis lúpica. Barranquilla, Colombia / Sociodemographic and clinical characteristics of patients with lupus nephritis. Barranquilla, Colombia

La Nefritis Lúpica (NL) es una complicación relevante del paciente con lupus eritematoso sistémico (LES). Las condiciones socio demográficas pueden ser vulnerables a la aparición de la enfermedad?. Estudio cuantitativo, descriptivo y transversal. Población conformada por 22 pacientes con (NL) del programa de Nefrored del Caribe que asistieron a una institución prestadora de salud en la ciudad de Barranquilla, de enero de 2017 a enero de 2018. La muestra fue por conveniencia. La información se realizó a través de instrumento tipo escala de Likert, conformada por las variables: características socio demográficas (sexo, ubicación geográfica, estado civil), tiempo de diagnóstico de la enfermedad y toma del medicamento ordenado. El 96% era de sexo femenino y el 4% de sexo masculino, 27.3% estuvo entre edades de 34 y 45 años, el 54.5% era procedente de la ciudad de Barranquilla, y el 2.7% de los pacientes tenìan diagnóstico en un plazo de tiempo menor a los 2 años de haber presentado manifestaciones clínicas. Las condiciones sociodemograficas y clinicas de los pacientes con LES que desarrollan NL permitirán desarrollar acciones para un diagnóstico oportuno e intervención efectiva que coadyuven a la adherencia al tratamiento, y a reducir la morbilidad en los pacientes de la Region Caribe Colombiana(AU)

Lupus Nephritis (LN) is a significant complication of the patient with systemic lupus erythematosus (SLE). Socio-demographic conditions may be vulnerable to the onset of the disease. This was a quantitative analytical and transversal study. Population comprised 22 patients with LN of the Renal Network of the Caribbean program attending a health care institution in the city of Barranquilla from January 2017 to January 2018. The sample was for convenience. The information was collected using a Likert scale instrument including these variables: socio-demographic characteristics (sex, geographical location, marital status), time of diagnosis of the disease, intake of medical prescription medicine. Ninety six percent was female and 4% male, 27.3% was between the ages of 34 and 45 years, 54.5% was from the city of Barranquilla, and 2.7% patients were diagnosed in a period of time lower than 2 years of having presented clinical manifestations. The socio-demographic and clinical conditions of patients with SLE that developed NL will allow developing actions for a timely diagnosis and effective intervention for better adherence to treatment, and reduce the morbidity associated with socio-demographic conditions that may influence patients in the Colombian Caribbean Region(AU)

Valorar el seguimiento y cumplimiento integral de adherencia al tratamiento en pacientes con nefritis lúpica / Rating Monitoring and Comprehensive Enforcement of Adherence to Treatment in Patients with Lupus Nephritis / Avaliar a perseguição e execução de integral de aderência ao tratamento em paciente com nefritis lúpica

Existen múltiples factores que están relacionados con la deficiente adherencia terapéutica farmacológica y no farmacológica. Objetivo: valorar el seguimiento y cumplimiento integral de adherencia al tratamiento en pacientes con nefritis lúpica en una institución prestadora de servicios de salud en Barranquilla, Colombia. Método: estudio retrospectivo en 2010-2014, aplicando dos medios para recolección de la información. Se diseñó una lista de chequeo, según los parámetros de la Guía de manejo para paciente renal en Colombia. Otros datos fueron extraídos de historias clínicas: sexo, edad, estado civil, nivel educativo, nivel socioeconómico, tiempo de diagnóstico, cumplimiento de controles y seguimiento interdisciplinar. Se estudiaron 51 registros clínicos que cumplieran con criterios de inclusión. Resultados: la enfermedad se presenta más en mujeres (90,2%), que hombres; la edad promedio fue de 28 a 32 años (60,8%); se atienden más a personas de bajos recursos económicos (43,1%); hay mayor procedencia del departamento del Atlántico (54,9%); el 33,3% de la población tiene un seguimiento entre 3 y 4 veces por año; por lo menos una vez han asistido a una consulta con médico general (100%) y una vez con nefrología; el 66,7% no cumple seguimiento de enfermería y el 59,8% asiste a evaluación nutricional (55%). La prednisolona fue el medicamento más ordenado y con mayor adherencia, y los de baja adherencia fueron: azatriopina, hidralazina, metilprednisolona y aspirina. Conclusión: se hace ineludible la valoración y seguimiento de manera precoz del tratamiento farmacológico y no farmacológico por el equipo interdisciplinario, para prevenir afecciones renales que lleven al deterioro del riñón y compliquen la salud del paciente.

There are multiple factors that are related to deficient pharmacological and non-pharmacological therapeutic adherence. Objective: To rating monitoring and comprehensive enforcement of adherence to treatment in patients with lupus nephritis in a provider institution health in Barranquilla-Colombia. Method: Retrospective study in the period 2010-2014, applying two means for data collection, designed a checklist, according to parameters of operation for kidney patient in Colombia, other data were extracted from medical records; such as sex, age, marital status, educational level, socio-economic, time of diagnosis, compliance controls and interdisciplinary monitoring. There were studied 51 clinical records that met inclusion criteria. Result: The disease is more common in women (90.2%) than men, average age 28 to 32 years (60.8%), low economic resource (43.1%), major origin from department Atlantic (54.9%). The 33.3% of the population is monitored 3 to 4 times per year, 100% at least 1 time attended a consultation with general practitioner, and 1 times with nephrology; 66.7% do not meet nursing monitoring, and 59.8% attend nutritional assessment (55%). Prednisolone was evident in higher percentage (88%) is the most orderly drug, and a low adhesion drugs: azathioprine, hydralazine, methylprednisolone and aspirin. Conclusion: It becomes unavoidable, assessment and monitoring of early stage pharmacological and non-pharmacological treatment by the interdisciplinary team, in order to prevent kidney diseases that lead to kidney impairment complicating the patient's health.

Tem vários fatores que estão relacionados com a farmacológica e não farmacológica adesão. Objetivo: Foi para avaliar a monitorização e conformidade total com a adesão ao tratamento em pacientes com lúpus nefrite na instituição de saúde que prestam Barranquilla, Colômbia. Método: no periodo de estudo retrospectivo em 2010-2014, foi utilizando os meios para recolher listas de informação e de acordo com os parámetros de manejo das guias de pacientes renales Colômbia, outros dados foram extraídos de prontuários; como; sexo, idade; estado civil; nível educacional; socioeconómico; tempo de diagnóstico, controles de conformidade e interdisciplinar. Em 51 registros clínicos que preencheram os critérios de inclusão foram estudados. Resultado: a doença é mais comum em mulheres (90,2%) do que em homens, com idade média de 28 a 32 anos (60,8%), baixo recurso económico (43,1%), departamento principal origem Atlântico (54,9%); a (33,3%). Da população é monitorado 3 a 4 vezes por año (100%), pelo menos 1 vez participaram de uma consulta com clínico geral, e 1 vezes com nefrologia; 66,7% não atendem acompanhamento de enfermagem, 59,8% participa avaliação nutricional (55%). O remédio prednisolona foi evidente em maior percentagem (88%) é a droga mais ordenada, e um baixo drogas de adesão: azatioprina, hidralazina, metilprednisolona e aspirina. Conclusão: torna-se inevitável, avaliação e monitoramento dos farmacológicos fase precoce e tratamento não farmacológico pela equipe interdisciplinar, a fim de prevenir doenças renais que levam à insuficiência renal que complica a saúde do paciente.

Glomerulonefritis rápidamente progresiva asociada a nefritis lúpica en una paciente de mediana edad / Quickly progressive glomerulonephritis associated with lupus nephritis in a middle age patient

Se describe el caso clínico de una paciente de 47 años de edad con antecedentes de síndrome linfoproliferativo, que fue ingresada en la sala de Hematología del Hospital General Docente Dr Juan Bruno Zayas Alfonso de Santiago de Cuba, y luego se le trasladó al Servicio de Nefrología por presentar dolor poliarticular, fiebre, edemas, disminución de la diuresis y aumento progresivo de la creatinina plasmática. El cuadro clínico y los exámenes complementarios permitieron diagnosticar una glomerulonefritis rápidamente progresiva como consecuencia de una nefritis lúpica de clase IV. La paciente fue tratada con prednisona y ciclofosfamida, y mostró una evolución satisfactoria sin necesidad de recurrir a tratamiento hemodialítico

The case report of a 47 years patient is described with a history of lymphoproliferative syndrome who was admitted at the Hematology room of Dr Juan Bruno Zayas Alfonso Teaching General Hospital in Santiago de Cuba, and then she was transferred to the Nephrology Service due to a polyarticular pain, fever, edemas, decrease of diuresis and progressive increase of the plasmatic creatinine. The clinical pattern and the lab tests allowed to diagnose a quickly progressive glomerulonephritis as consequence of a lupus nephritis class IV. The patient was treated with prednisone and cyclophosphamide, and she showed a satisfactory clinical course without the necessity of using hemodyalisis treatment

Correlación clínico patológica y evolución de la nefropatía lúpica en niños y adolescentes / Clinicopathologic correlation and evolution of lupus nephritis in children and adolescents

El lupus eritematoso sistémico (LES) tiene una prevalencia baja en la población general y es menor en la edad pediátrica. La nefropatía lúpica (NL) es más frecuente y de mayor severidad que en adultos, condicionando la morbimortalidad de la enfermedad. Se realizó un estudio descriptivo prospectivo de 20 niños y adolescentes con NL controlados en la Policlínica de Colagenopatías del Centro Hospitalario Pereira Rossell en el período desde octubre de 2003 hasta setiembre de 2013 con el objetivo de describir las características clínico-serológicas y evolutivas de pacientes con NL y correlacionarlas con los hallazgos anátomopatológicos. La NL se observó en el 52,6% de los casos con LES. El 70% fueron de sexo femenino, relación femenino/masculino de 2,3/1, 85% de raza blanca, la mediana del diagnóstico fue de 12 años. Las formas de presentación fueron: alteraciones urinarias menores (AUM) en 14 pacientes (0,7), en cuatro casos síndrome nefrótico (SN), con o sin insuficiencia renal (IR) y/o hipertensión arterial. Un paciente se manifestó con síndrome nefrítico. Un paciente tenía un examen de orina normal. Las formas histopatológicas proliferativas graves se presentaron en 18 (0,9); los casos con AUM presentaban NL grado III-IV en 13 (0,93); todos los casos con SN con o sin IR tenían NL III-IV. No hubo casos de NL aislada como forma de comienzo. En el momento del diagnóstico, los anticuerpos antinucleares fueron positivos en 19 (0,95) y los anti DNA doble cadena en 16 (0,8); C3 y C4 estuvieron descendidos en 19 (0,95) y en 15 (0,75) respectivamente. El seguimiento promedio fue 4,2 años. Al final del seguimiento estaban en remisión 16 pacientes (0,8), cuatro en remisión parcial, todos con función renal normal, excepto un caso que presentó IR extrema, fue trasplantado y tuvo una excelente evolución. Un paciente falleció con hemorragia pulmonar. La sobrevida de la función renal y la de los pacientes fue 0,95 respectivamente. El tratamiento se realizó en base a corticoides, hidroxicloroquina asociados a azatioprina o micofenolato mofetilo. En ocho pacientes con cuadros graves se usó la ciclofosfamida I/V. Esta serie constituye la primera serie nacional de nefropatía lúpica en niños y adolescentes. Conclusión: predominó la presentación clínica con AUM y formas histopatológicas severas, clases III y IV, evidenciando una disociación clínico anatomopatológica. A pesar del elevado porcentaje de NL severas, el manejo adecuado y oportuno y la adherencia al tratamiento y a los controles médicos fueron fundamentales para la evolución favorable de la NL.

Systemic lupus erythematosus (SLE) has a low prevalence in the overall general population and this is lower in children. Child lupus nephropathy (LN) is more frequent and severe than in SLE adult patients, with greater disease morbidity and mortality. A prospective descriptive study of 20 children and adolescents with LN monitored in the Collagen Diseases Office of the Pereira Rossell Hospital between October, 2003 and September, 2013 was performed. The objective of this study was to describe clinical-serological features and the evolution of these patients and to correlate them with its anatomopathological findings. LN was diagnosed in 52,6% of the SLE patients, 70% were female with a female/male correlation of 2,3/1; 85% were Caucasian; median age at diagnosis was 12 years old. The clinical presentations were minor urinary findings (MUF) in 14 patients (0,7) and nephrotic syndrome (NS) in 4 (0,2), and another one nephritic syndrome. One patient presented no symptoms and had normal urinalysis. Severe proliferative classes predominated in18 patients (0.9); 13 (0.93) patients with MUF and all the patients with NS had LN classes III or IV. Isolated LN was not seen in the initial presentation. At the time of diagnosis antinuclear antibodies were positive in 19 patients (0.95); and anti DNA double stranded in 16 (0.8). Low C3 was found in 19 (0.95) and C4 in 15 (0.75), respectively. Average follow-up time was 4.2 years. At the end of follow-up 16 (0.8) were in remission, 4 of them in partial remission; all patients presented normal renal function except for one who evidenced severe renal failure and required hemodialysis and transplantation and had an excellent evolution. One patient died with pulmonary hemorrhage. The renal and patient survivals were 0.95 respectively. Treatment consisted in corticosteroids and hydroxychloroquine associated with azathioprine or mycophenolate mofetil. Cyclophosphamide was administered to 8 patients with severe illness. This is the first national report of LN in children and adolescents. Conclusions: the predominant clinical presentation of LN was MUF with severe anatomopathological findings, classes III and IV, showing a clinical-pathological dissociation. Despite the high percentage of severe LN, early and adequate treatment, as well as a good compliance to it with periodic medical follow-up, were essential to achieve a favorable outcome of LN.

Frequência e avaliação clínico-histológica das doenças glomerulares em um hospital terciário da região Sul do Brasil / Frequency and clinical histological analysis of glomerular diseases in a tertiary hospital in southern Brazil

Resumo Introdução: As glomerulopatias são as doenças renais mais frequentemente diagnosticáveis por biópsia. O levantamento epidemiológico das glomerulopatias permite identificar sua distribuição e principais etiologias e serve de subsídio para definição de estratégias de prevenção e tratamento. Objetivo: O presente estudo pretende identificar a frequência e a correlação clínico-patológica das glomerulopatias diagnosticadas por biópsia no HC-UFPR durante 5 anos. Métodos: Foram realizadas 131 biópsias no período de 1 de janeiro de 2008 a 31 de dezembro de 2012, submetidas à microscopia óptica e de imunofluorescência. Todas as lâminas de microscopia óptica foram revistas por um patologista. Dados clínicos e laboratoriais e resultados da microscopia de imunofluorescência foram obtidos por revisão dos prontuários. Resultados: Foram reanalisados 128 de 131 casos; 46,5% foram obtidos em homens. A idade média de realização da biópsia foi 43 anos para os homens e 38 anos para as mulheres. Em 99 casos identificou-se a indicação da biópsia; 49,5% apresentaram síndrome nefrótica; 17,17%, insuficiência renal aguda e 15,15% insuficiência renal crônica; 8,08%, síndrome nefrítica; 6,06%, proteinúria isolada e 4,04%, hematúria isolada. 61,21% tratavam-se de glomerulopatia secundária, 33,62% glomerulopatia primária e 5,17% não puderam ser classificados. Dentre as glomerulopatias secundárias, a mais frequente foi a nefrite lúpica (49,29%), e, dentre as primárias, glomeruloesclerose segmentar e focal (30,77%) e nefropatia membranosa (25,64%). Conclusão: O paciente com glomerulopatia neste serviço é adulto e portador de síndrome nefrótica. Ao contrário de outros relatos, observamos predomínio das glomerulopatias secundárias, refletindo possivelmente o perfil terciário de atendimento do HC-UFPR.

Resumo Introduction: The glomerulopathies are the most common biopsy-proven kidney diseases. The epidemiological investigation of glomerulopathies allows the identification of their distribution and main causes and enables the development of prevention and treatment strategies. Objective: This study aims to identify the frequency and clinical-pathological correlation of glomerular diseases diagnosed at the HC-UFPR over the period of 5 years. Methods: 131 biopsies were performed between January 1, 2008 and December 31, 2012 and were analysed by light and immunofluorescence microscopy. Histopathological slides were reviewed by a pathologist. Clinical and laboratory data and the immunofluorescence microscopy results were extracted from medical records. The findings were tabulated and analysed. Results: 128 of 131 cases were reanalysed. 46.5% were obtained from men. Patients' age averaged 43 years for men and 38 for women. In 99 cases, the indication of biopsy was identified; 49.5% cases presented nephrotic syndrome, 17.17%, acute renal failure and 15.15%, chronic renal failure; 8.08%, nephritic syndrome; 6.06%, isolated proteinuria and 4.04% isolated hematuria. In 61.21% an underlying disease related to the glomerulopathy could be identified; 33.62% corresponded to primary disease and in 5.17% of cases the nature of the glomerulopathy could not be determined. Among secondary glomerulopathies, the most frequent was Lupus Nephritis (49.29%), and among the primary, Focal Segmental Glomerulosclerosis (30.77%) and Membranous Nephropathy (25.64%). Conclusion: The average patient with glomerulopathy in this service is an adult with nephrotic syndrome. Unlike other reports, secondary glomerulopathies were predominant. These findings may reflect the tertiary characteristic of the assistance at HC-UFPR.

Mujer joven con nefritis lúpica y dengue / Young woman with lupus nephritis and dengue

Se reporta caso clínico de una mujer de 21 años con lupus eritematoso sistémico (LES) de diagnóstico reciente complicada con nefritis lúpica (NL) tratada en nuestro centro, con evolución favorable con inmunosupresores. Pero reingresa por dengue con signos de alarma del cual se recupera satisfactoriamente.

Clinical case of a 21 year old woman with complicated systemic lupus erythem atosus (SLE) recently diagnosed with lupus nephritis (LN) treated at our center, with favorable evolution immunosuppression reported. But readmitted because dengue of with warning signs, at present he is recovering satisfactorily

Consenso da Sociedade Brasileira de Reumatologia para o diagnóstico, manejo e tratamento da nefrite lúpica / Consensus of the Brazilian Society of Rheumatology for the diagnosis, management and treatment of lupus nephritis

Objetivo Elaborar recomendações para o diagnóstico, manejo e tratamento da nefrite lúpica no Brasil. Método Revisão extensa da literatura com seleção dos artigos com base na força de evidência científica e opinião dos membros da Comissão de Lúpus Eritematoso Sistêmico da Sociedade Brasileira de Reumatologia. Resultados e conclusões 1) A biópsia renal deve ser feita sempre que possível e houver indicação e quando não for possível, o tratamento deve ser orientado com base na inferência da clase histológica. 2) Devem ser implementados medidas e cuidados idealmente antes do início do tratamento, com ênfase na atenção ao risco de infecção. 3) Devem-se compartilhar riscos e benefícios do tratamento com pacientes e familiares. 4) O uso da hidroxicloroquina (preferencialmente) ou difosfato de cloroquina é recomendado para todos os pacientes (exceto contraindicação) durante as fases de indução e manutenção. 5) A avaliação da eficácia do tratamento deve ser feita com critérios objetivos de resposta (remissão completa/remissão parcial/refratariedade). 6) Os IECA e/ou BRA são recomendados como antiproteinúricos para todos os pacientes (exceto contraindicação). 7) A identificação de sinais clínicos e/ou laboratoriais sugestivos de GN laboratoriais sugestivos de glomerulonefrite proliferativa ou membranosa deve indicar início imediato de terapia específica incluindo corticosteroides e agente imunossupressor, mesmo que não seja possível comprovação histológica. 8) O tempo de uso dos imunossupressores deve ser no mínimo de 36 meses, mas eles podem ser mantidos por períodos mais longos. A sua suspensão só deve ser feita quando o paciente atingir e mantiver remissão completa sustentada. 9) Deve-se considerar nefrite lúpica refratária quando a remissão completa ou parcial não for alcançada após 12 meses de tratamento adequado, quando uma nova biópsia renal deve ser considerada para auxiliar na identificação da causa da refratariedade e decisão terapêutica. .

Objective To develop recommendations for the diagnosis, management and treatment of lupus nephritis in Brazil. Method Extensive literature review with a selection of papers based on the strength of scientific evidence and opinion of the Commission on Systemic Lupus Erythematosus members, Brazilian Society of Rheumatology. Results and conclusions (1) Renal biopsy should be performed whenever possible and if this procedure is indicated; and, when the procedure is not possible, the treatment should be guided with the inference of histologic class. (2) Ideally, measures and precautions should be implemented before starting treatment, with emphasis on attention to the risk of infection. (3) Risks and benefits of treatment should be shared with the patient and his/her family. (4) The use of hydroxychloroquine (preferably) or chloroquine diphosphate is recommended for all patients (unless contraindicated) during induction and maintenance phases. (5) The evaluation of the effectiveness of treatment should be made with objective criteria of response (complete remission/partial remission/refractoriness). (6) Angiotensin-converting enzyme inhibitors and/or angiotensin receptor blockers are recommended as antiproteinuric agents for all patients (unless contraindicated). (7) The identification of clinical and/or laboratory signs suggestive of proliferative or membranous glomerulonephritis should indicate an immediate implementation of specific therapy, including corticosteroids and an immunosuppressive agent, even though histological confirmation is not possible. (8) Immunosuppressives must be used during at least 36 months, but these medications can be kept for longer periods. Its discontinuation should only be done when the patient could achieve and maintain a sustained and complete remission. (9) Lupus nephritis should be considered as refractory when a full or partial remission is not achieved after 12 months of an appropriate treatment, when ...

Pulmonary hypertension in systemic lupus erythematosus: an independent predictor of patient survival

BACKGROUND/AIMS: We investigated whether transthoracic echocardiography-suspected pulmonary hypertension (PH) affects survival in systemic lupus erythematosus (SLE) patients and examined factors associated with PH occurrence and survival. METHODS: This retrospective single-center study included 154 Korean SLE patients fulfilling the American College of Rheumatology criteria (January 1995 to June 2013). Student t test, Mann-Whitney U test, Kaplan-Meier curves, and log-rank tests were used for comparisons. RESULTS: A total of 35 SLE patients with PH (SLE/PH+) and 119 without PH (SLE/PH-) were analyzed. Higher percentages of interstitial lung disease, Raynaud's phenomenon (RP), World Health Organization functional classification III/IV, and cardiomegaly were found in SLE/PH+ compared to SLE/PH-. Furthermore, the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index was significantly higher in SLE/PH+ (2.46 +/- 1.245 vs. 1.00 +/- 1.235), whereas survival rates were significantly higher in SLE/PH- in log-rank tests (p = 0.001). In multivariate analysis, the adjusted mortality hazard ratio (HR) for SLE/PH+ patients was 3.10. Subgroup analysis demonstrated a higher percentage of lupus nephritis in the SLE/PH+ patients who died (p = 0.039) and low complement-3 levels (p = 0.007). In univariate analysis, the mortality HR for SLE/PH+ patients with lupus nephritis was 4.62, whereas the presence of RP decreased the mortality risk in multivariate analysis; adjusted HR, 0.10. CONCLUSIONS: PH is an independent factor predicting survival in SLE patients. The presence of lupus nephritis resulted in an increased trend for mortality, whereas coexistence of RP was associated with a better survival prognosis in SLE/PH+ patients.

Clinical characteristics of male and female Korean patients with systemic lupus erythematosus: a comparative study

BACKGROUND/AIMS: To compare the clinical characteristics and outcomes of systemic lupus erythematosus between male and female Korean patients. METHODS: A retrospective analysis was performed at a single tertiary hospital from August 1994 to May 2010. Male patients were matched with two to three female patients based on age and disease duration. Organ damage was assessed using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index (SLICC/ACR DI). RESULTS: Fifty-three male patients were compared with 150 female patients. Renal disorders were found more frequently in male patients at disease onset (p < 0.001); the adjusted odds ratio (OR) demonstrated a significant sex preponderance for renal manifestations (OR, 3.26; 95% confidence interval [CI], 1.62 to 6.57). Diffuse proliferative lupus nephritis and end-stage renal disease requiring dialysis during the disease course were more prevalent in male patients (p = 0.025 and p < 0.001, respectively). The risk for requiring long-term dialysis was significantly higher in male than in female patients (OR, 4.02; 95% CI, 1.07 to 15.06), as was the mean SLICC/ACR DI (1.55 +/- 1.35 vs. 1.02 +/- 1.57, respectively; p = 0.028). CONCLUSIONS: Our data demonstrate that Korean patients with lupus have characteristics similar to those of cohorts reported previously. Male patients had significantly higher incidences of renal manifestations and organ damage.

[Systemic lupus erythematosus [SLE] in pregnancy and severe nephritis [a case-report]]

Nephritis is one of the most dangerous presentations of SLE. Lupus in pregnancy can increase maternal and fetal mortality. In this report a pregnant woman with lupus nephritis is presented. A thirty year old woman in 30th week of pregnancy was admitted to internal medicine ward for evaluation of peripheral edema and hypertension. Important findings of her laboratory exam were: azotemia, hematuria, proteinuria, anemia, large size kidneys, active urine sediment, pleural and pericardial effusion, ascites, high titer of ANA, anti double strand DNA and lupus anticoagulant. Renal biopsy was done, pulse of methyl prednisolon prescribed and hemodialysis was started. After delivery, pulse of cyclophosphamide was also given and her renal function improved. The patient had not history of rheumatologic disease and the first presentation of lupus was severe nephritis during pregnancy. Fortunately, the response of patient to the treatment was good. After about 3-years follow-up, patient's renal function is normal and her son seems healthy

Methimazole-Induced Bullous Systemic Lupus Erythematosus: A Case Report

Bullous systemic lupus erythematosus (SLE) is a kind of LE-non-specific bullous skin disease that is rarely induced by a medication. We describe the first case of bullous SLE to develop after administration of methimazole. A 31-yr-old woman presented with generalized erythematous patches, multiple bullae, arthralgia, fever, conjunctivitis, and hemolytic anemia. Biopsy of her bulla showed linear deposition of lgG, lgA, C3, fibrinogen, and C1q at dermo-epidermal junction. She was diagnosed as bullous SLE and treated with prednisolone, dapsone, hydroxychloroquine, and methotrexate. Our experience suggests that SLE should be considered as a differential diagnosis when bullous skin lesions develop in patients being treated for hyperthyroidism.

Características clínicas y hallazgos histopatológicos de glomerulonefritis lúpica en pacientes con Rhupus en el Hospital Nacional Arzobispo Loayza en los años 2003 al 2009 / Clinical features and histopathological findings in Rhupus patients developing glomerulonephritis in Arzobispo Loayza Nacional Hospital between 2003 and 2009

Hasta el 10% de pacientes con Lupus Eritematoso sistémico tienen la artropatía similar a Artritis Reumatoide, denominado ôRuphusõ. En estos pacientes prevalecen los signos y síntomas de Artritis reumatoide y el compromiso renal está asociado con Lupus. Objetivo: Describir las características clínicas y hallazgos histopatológicos renales en pacientes con Ruphus. Materiales y métodos: Reporte de Casos detectados en forma retrospectiva en el Hospital Nacional Arzobispo Loayza, entre los años 2003 al 2009 y sus biopsias renales. Resultados: Hubo 7 pacientes con ruphus, la mediana de edad fue 40 años, una mediana de tiempo de evolución de 2 años. Los hallazgos histopatológicos renales relevantes fueron Glomerulonefritis lúpica tipo IV en 5 pacientes; proteinuria entre 288 a 2560 mg/24 horas y títulos de Factor Reumatoide entre 14 a 34,6 UI/L. Conclusiones: Los pacientes reportados a diferencia de la literatura fueron de mayor edad, con compromiso renal moderado a severo relacionado a Lupus.

Up to 10% of patients with Systemic Lupus Erythematosus have a joint condition similar to that of rheumatoid arthritis, which is called ôRhupusõ. These patients predominantly have signs and symptoms of rheumatoid arthritis and kidney damage associated with Lupus. Objectives: To describe the clinical characteristics and the renal histopathological findings in patients with rhupus. Materials and methods: Retrospective review of case reports and kidney biopsies from patients seen from 2003 to 2009 in Arzobispo Loayza National Hospital. Results: There were 7 patients with rhupus; their median age was 40 years, the median time of disease progression was 2 years. Most relevant renal histopathological findings were type IV glomerulonephritis in 5 patients; proteinuria between 288 to 2560 mg/24 hours and rheumatoid factor titers between14 to 34.6 UI/L were also found. Conclusions: Patients were older compared to others previously reported previously in the literature. Lupus-related renal damage was moderateto severe.