Anca-associated crescentic glomerulonephritis in a child with isolated renal involvement / Glomerulonefrite rapidamente progressiva associada a ANCA em uma criança com acometimento renal isolado

ABSTRACT Pauci-immune glomerulonephritis (GN) is more common in elderly people compared to children and the etiology is not completely understood yet. Antineutrophil cytoplasmic antibody (ANCA) positivity occurs in 80% of the patients. We report a case of a 7-year-old girl who presented with malaise and mildly elevated creatinine diagnosed as ANCA-associated pauci-immune crescentic glomerulonephritis with crescents in 20 of 25 glomeruli (80%). Of these 20 crescents, 12 were cellular, 4 fibrocellular, and 4 globally sclerotic. She did not have purpura, arthritis, or systemic symptoms and she responded well to initial immunosuppressive treatment despite relatively severe histopathology. The patient was given three pulses of intravenous methylprednisolone (30 mg/kg on alternate days) initially and continued with cyclophosphamide (CYC; 2 mg/kg per day) orally for 3 months with prednisone (1 mg/kg per day). In one month, remission was achieved with normal serum creatinine and prednisone was gradually tapered. The case of this child with a relatively rare pediatric disease emphasizes the importance of early and aggressive immunosuppressive treatment in patients with renal-limited ANCA-associated pauci-immune crescentic GN even if with a mild clinical presentation. As in our patient, clinical and laboratory findings might not always exactly reflect the severity of renal histopathology and thus kidney biopsy is mandatory in such children to guide the clinical management and predict prognosis.

RESUMO A glomerulonefrite (GN) pauci-imune é mais comum em idosos em comparação com crianças, e a etiologia ainda não é completamente compreendida. A positividade do anticorpo citoplasmático antineutrófilo (ANCA) ocorre em 80% dos pacientes. Relatamos o caso de uma menina de 7 anos de idade que apresentou mal-estar e creatinina discretamente elevada, diagnosticada como glomerulonefrite rapidamente progressiva pauci-imune associada a ANCA com crescentes em 20 dos 25 glomérulos (80%). Destes 20 crescentes, 12 eram celulares, 4 fibrocelulares e 4 globalmente escleróticos. Ela não apresentava púrpura, artrite ou sintomas sistêmicos e respondeu bem ao tratamento imunossupressor inicial, apesar da histopatologia relativamente grave. A paciente recebeu três pulsos de metilprednisolona intravenosa (30 mg/kg em dias alternados) inicialmente e continuou com ciclofosfamida (2 mg/kg por dia) por via oral durante 3 meses com prednisona (1 mg/kg por dia). Em um mês, a remissão foi alcançada com creatinina sérica normal e a prednisona foi gradualmente reduzida. O caso desta criança com uma doença pediátrica relativamente rara enfatiza a importância do tratamento imunossupressor precoce e agressivo em pacientes com GN rapidamente progressiva renal associada à ANCA, mesmo com uma apresentação clínica leve. Como em nossa paciente, os achados clínicos e laboratoriais podem nem sempre refletir exatamente a gravidade da histopatologia renal e, assim, a biópsia renal é obrigatória nessas crianças para orientar a conduta clínica e auxiliar no prognóstico.

Trastornos glomerulares en la práctica médica / Glomerulopathies in the medical practice

RESUMEN Las glomerulopatías agrupan varias nefropatías con lesiones fundamentalmente del corpúsculo renal y que se expresan principalmente por proteinuria, hematuria, edemas e hipertensión arterial. La presentación clínica varía en dependencia del tipo de enfermedad de que se trate. Constituye la causa más frecuente de enfermedad renal crónica en adultos jóvenes, por lo que su estudio resulta imprescindible sobre todo para el nivel primario de salud. El propósito fue actualizar consideraciones pertinentes sobre la conducta diagnóstica y terapéutica integral ante una glomerulopatía y valorar emisión de recomendaciones al respecto. Se realizó una búsqueda, análisis y síntesis de información a través de Bases de datos ScieLO Cuba, ScieLO regional, Pubmed, Cumed, Clinical Key en el período 2012-2017 con las palabras clave: síndrome nefrótico, glomerulonefritis, diagnóstico, terapéutica, atención integral. El abordaje en las glomerulopatías es integral, multidisciplinario e individualizado. En Cuba constituyen la cuarta causa de enfermedad renal crónica y predomina el síndrome nefrítico agudo postinfeccioso. El método clínico juega en ello un papel trascendental a la hora de reconocer y registrar sus aspectos clínicos, su etiología, su fisiopatología, y los exámenes complementarios que confirman su presencia o sus complicaciones, así como un tratamiento oportuno que garanticen el perfeccionamiento asistencial. El arma más poderosa ante el reto de los trastornos glomerulares es la visión integradora y con enfoque individual y social protagonizado por el médico ante este grupo de nefropatías en adultos.

ABSTRACT Glomerulopathies encompass a group of several renal disorders with lesions, mainly in the renal corpuscle, expressed in proteinuria, hematuria, edemas and arterial hypertension. Their clinical manifestations change in dependence of the kind of disease. They are the most frequent cause of chronic renal disease in young adults; therefore their study is very important above all in the health care primary level. The aim was updating pertinent considerations on the diagnostic behavior and comprehensive therapy in the case of glomerulopathy, and evaluating the emission of recommendations regarding to them. A search, analysis and synthesis of information was carried out in the databases ScieLO Cuba, ScieLO regional, Pubmed, Cumed, and Clinical Key in the period 2012-2017, using the key words nephrotic syndrome, glomerulonephritis, diagnosis, therapeutics, comprehensive care. The approach to glomerulopathies is comprehensive, multidisciplinary and individualized. They are the fourth cause of chronic renal disease; the acute post-infectious nephritic syndrome predominates. The clinical method plays a transcendental role at the moment of recognizing and registering their clinical characteristics, etiology and physiopathology, while complementary tests confirm their presence or complications, and therefore an opportune treatment guarantying the healthcare improvement. The most powerful weapon against the challenge of the glomerular disorders is the integrated vision with an individual and social approach led by the physician in the case of these nephropathies in adults.

Anticuerpos contra la cardiolipina en glomerulonefritis postestreptocócica concurrente con anemia hemolítica autoinmunitaria: a propósito de un caso / Anticardiolipin antibodies in concurrent poststreptococcal glomerulonephritis and autoimmune hemolytic anemia: A case report

En este artículo, presentamos el caso de una paciente con glomerulonefritis aguda postestreptocócica (GNAPE) y anemia hemolítica autoinmunitaria (AHAI). Además de los signos típicos de la GNAPE, la paciente tuvo un resultado positivo en la prueba de antiglobulina directa y anticuerpos contra la cardiolipina sin que presentara las manifestaciones clínicas típicas del síndrome antifosfolipídico. Este caso genera dudas respecto de la relación entre el estreptococo y el desarrollo de anemia hemolítica autoinmunitaria en los niños. Este caso destaca la posibilidad de que las infecciones estreptocócicas de nuestra paciente podrían haber causado la anemia, ya sea en el contexto de anticuerpos antifosfolipídicos preexistentes o por haber desencadenado el desarrollo de anticuerpos patogénicos, que luego lleva a la presentación clínica de hemólisis. Se presume que, en la paciente, los anticuerpos contra la cardiolipina inducidos por la infección estreptocócica podrían tener una función directa en la presentación clínica de AHAI.

We present a case of acute post-streptococcal glomerulonephritis (APSGN) with autoimmune hemolytic anemia (AIHA). Along with the classic findings of APSGN, the patient had a positive direct antiglobulin test and an anticardiolipin antibody without any typical clinical manifestations of antiphospholipid syndrome (APS). This case raises questions of the relationship between Streptococcus and the development of autoimmune hemolytic anemia in children. Our case highlights the possibility that the streptococcal infections in this patient might be responsible for her anemia, either in setting of underlying antiphospholipid antibodies, or in having triggered the development of pathogenic antibodies, which subsequently leads to the clinical evolution of hemolysis. It is presumed that in our case, the anticardiolipin antibody induced by streptococcal infection may play a direct role in the clinical evolution of AIHA.

ANCA-Positive pauci-immune crescentic glomerulonephritis in a patient with systemic lupus erythematosus / Glomerulonefrite rapidamente progressiva ANCA-Positiva pauci-imune em paciente com lúpus eritematoso sistêmico

Abstract The pauci-immune crescentic glomerulonephritis (PICGN) is generally associated with small-vessel vasculitis with a few reported cases associated with other autoimmune diseases such as Systemic Lupus Erythematosus (SLE). We present the case of a female 34-year-old patient with acute kidney injury symptoms with indication for renal replacement therapy in the context of clinical SLE diagnosis. A kidney biopsy was conducted and it was found that most glomeruli showed some segmental sclerosis with synechia to the Bowman's capsule. 67% of the glomeruli had fibroepithelial crescents. Moreover, the interstitial space had a moderate lymphomononuclear infiltration and mild fibrosis. In the arterioles, there were walls thickened by subintimal sclerosis. Direct immunofluorescence detected limited IgM and C3 deposits in capillary loops and negative mensangium for IgG, IgA and C1q. A therapy using corticosteroids and intravenous cyclophosphamide was initiated with stable evolution. PICGN associated with SLE is a rare pathology with clinical presentation, varied evolution and without a standard medical treatment.

Resumo A glomerulonefrite rapidamente progressiva pauci-imune apresenta-se geralmente associada a vasculite de pequenos vasos, com poucos casos associados a outras doenças imunes como o lúpus eritematoso sistêmico (LES). Apresentamos no presente artigo o caso de uma mulher de 34 anos de idade com sintomas de insuficiência renal aguda e indicação de terapia renal substitutiva, no contexto de diagnóstico clínico de LES. A biópsia renal realizada revelou que a maioria dos glomérulos apresentavam um certo grau de esclerose segmentar e sinéquias com a cápsula de Bowman. Sessenta e sete por cento dos glomérulos apresentava crescentes fibroepiteliais. Além disso, o espaço intersticial exibia infiltrado linfomononuclear moderado e fibrose discreta. Nas arteríolas, as paredes encontravam-se espessadas por esclerose subintimal. A imunofluorescência direta detectou depósitos limitados de IgM e C3 nas alças capilares e mesângio negativo para IgG, IgA e C1q. Tratamento com corticosteroides e ciclofosfamida endovenosa foi iniciado com evolução estável. A glomerulonefrite rapidamente progressiva pauci-imune associada a LES é uma patologia rara com manifestação clínica e evolução variada, sem tratamento clínico padronizado.

Frequency of antineurtophil cytoplasmic antibody in glomerulonephritis

Aim of the study was to determine the frequency of antineutrophil cytoplasmic antibody [ANCA] [p-ANCA and c-ANCA] in clinically diagnosed glomerulonephritis. Autoimmune diseases including systemic vasculitis, affect a large number of people ill whom the leading cause of morbidity and mortality is glomerulonephritis that is often associated with chronic kidney disease. There are many risk factors for kidney diseases such as chronic inflammation, auto-immune diseases, immunosuppressive therapy, etc. Early phases of renal injury in autoimmune patients are clinically silent. For the detection of nephron damage, histopathological examination is gold standard but detection of antineutrophil cytoplasmic antibody [ANCA] can be used to find out early nephron damage. Design was analytical Cross-sectional. The study was conducted at the Department of Immunology, University of Health Sciences, Lahore in a period of November 2008 to October 2009. Study included 64 clinically diagnosed of glomerulonephritis. Levels of ANCA [MPO and PR3] were determined by ELISA technique. Out of which four [6.25%] patients showed positive reaction to myeloperoxidase [MPO] antigen while1 [1.56%] patient was positive for proteinase-3 [PR3] antigen. In 40-60 years of patients, sero-positivity for MPO and PR3 was 14% and 3.6% respectively, p-value for MPO and PR3 was <0.05 and >0.05 respectively. We concluded that glomerulonephritis is better related with MPO-ANCA than PR3-ANCA. The difference in the levels of MPO-ANCA in different age groups was significant but it was non-significant among different genders. Difference in the levels of PR3-ANCA was not significant for both age and gender

Imagecytometry: a new tool for diagnosis of glomerular haematuria.

Differentiation between glomerular and nonglomerular haematuria is a major challenge in clinical medicine, which is very important for a definitive diagnosis and management in individual cases. Phase contrast microscopy of red cells in urine is the standard practice for diagnosis of glomerular haematuria. Urine cell flowcytometry is recently being used for such diagnosis. In this context, the role of determination of haemoglobin content of urine red cells is not know. Application of image analysis to study the red cells in urine may be more objective and accurate for the diagnosis. The present study has been undertaken to evaluate the urine red cells with the help of an automated computerized image analysis system for determination of hemoglobin content by integrated optical density (IOD). The morphometric parameters were also analyzed. The glomerular RBCs were significantly smaller in diameter, area and perimeter than nonglomerular RBCs with a greater variation in shape and lower [OD (p<0.0001 to <0.00002). With the help of morphometric parameters the percentage of cases diagnosed correctly varied from 90 to 95. The IOD helped to diagnose 100% cases. Thus application of this new technique may be very useful diagnostic tool in the investigation of haematuria.

Reversäo do dismorfismo eritrocitário urinário pelo furosemida / Dismorphism reversion of urinary eritrocyte by furosemide

A localizaçäo da origem da hematúria a partir da morfologia das hemácias é um método amplamente utilizado. No presente trabalho, os autores demonstram que a administraçäo do Furosemida reverte um padräo dismórfico (glomerular) para isomórfico (pós-glomerular) da hematúria. Sugerem que a análise da morfologia das hemácias näo deveria ser realizada na vigência da diuréticoterapia e que as alteraçöes de forma e tamanho das hemácias urinárias observadas em pacientes com glomerulonefrites ocorrem principalmente no néfron distal.

Heterogeneity of antibody response to glomerular basement membrane antigen in patients with different forms of glomerulonephritis.

Antibodies to collagenous and noncollagenous components of glomerular basement membrane (GBM) have been detected by immunoblotting in some sera from patients with various kinds of glomerulonephritis. A half proportion of patients with rapidly progressive glomerulonephritis (RPGN), chronic focal glomerulonephritis (CFGN), idiopathic membranous glomerulonephritis (MGN). IgA nephropathy and lupus nephritis (LE-GN) had IgG antibodies to heterogenous components in acid insoluble fraction of pepsin digested GBM. This acid insoluble fraction represented a complex of collagen and noncollagenous proteins of GBM. Following digestion of acid insoluble fraction with bacterial collagenase, the triple helical collagenous components of GBM were destroyed and released most likely of noncollagenous proteins. Antibodies to this noncollagenous proteins were found in only some patients with chronic glomerulonephritis (17.6%) and lupus nephritis (21.4%). Upon reaction with human placenta derived type IV collagen, different frequencies of antibody response were found in patients of different groups. However, all these reactive sera showed a similar immunoblotting pattern. The relationship between antibody response to antigenic components from human GBM or human placenta and pathogenesis of renal disease is unclear. However, the occurrence of spontaneous autoantibody response to some exposed GBM self antigens may mediate further renal destruction resulting in chronic ongoing stage of the disease.

Platelet serotonergic mechanisms and glomerulonephritis.

Proven cases (28) of glomerulonephritis (GN) were evaluated for clinico-biochemical profile, bleeding time, platelet count, platelet aggregation and platelet serotonergic mechanisms. Inordinate increase in platelet aggregation and altered platelet serotonergic mechanisms (reduced 5-HT, uptake, reduced intraplatelet 5-HT and increased plasma 5-HT) were demonstrated in some histopathological types of GN. The mechanisms and importance of these alterations have been discussed.

Acido siálico em glomerulonefrite difusa aguda pós-estreptocócica: um marcador válido? / Sialic acid in diffuse acute post-streptococcic glomerulonephritis: a valid marka?

Utilizando um método colorimétrico de dosagem de ácido siálico livre, que depende de sua reaçäo com o ácido tiobarbitúrico, estudamos 49 pacientes com GNDAPE, que foram comparados a 25 indivíduos normais. Quarenta e um por cento dos pacientes apresentavam valores elevados e significantemente maiores que os do grupo controle. A sensibilidade e especificidade do método foram respectivamente de 41% e 96%. Näo houve correlaçäo entre dosagem de ácido siálico livre e precocidade de nefrite clínica ou entre uréia plasmática e níveis de C3 séricos

Ativaçäo do sistema complemento: estudo em 100 crianças portadoras de glomerulonefrite aguda pós-infecciosa (GNAPI) / Activation of the complement system: study in 100 children with acute post infections glomerulonephritis

Em 100 crianças portadoras de glomerulonefrite aguda pós-infecciosa (GNAPI) foram analisados os níveis séricos de C3, C4 e CH50. Durante as primeiras quatro semanas de evoluçäo demonstraram-se níveis séricos inferiores ao normal em todas as 97 determinaçöes de C3 (X =34,8 + ou - 13,2 mg/dl 0 - 2 semanas e 48,2 + ou - 18,2 mg/dl 2 - 4 semanas) e em 38 de 98 determinaçöes de C4 (X = 24,3 + ou - 11,6 mg/dl 0 - 2 semanas e 30,1 + ou - 12,5 mg/dl 2 - 4 semanas). A maioria das determinaçöes realizadas pós quatro semanas de evoluçäo demonstrou níveis séricos normais de C3, C4 e CH50. Houve predomínio da via alternativa (60%) em relaçäo à clássica (40%), independente do sexo e foco infeccioso. Os autores discutem a ativaçäo do sistema complemento em GNAPI

Estudio longitudinal de las concetraciones de C3 y C4 del complemento sérico en glomerulonefritis aguda del niño / Longitudinal study of C3 and C4 concentrations of serum complement in acute glomerulonephritis of the child

Se estudiaron 54 niños portadores de glomerulonefritis aguda admitidos al Servicio de Nefrología Pediátrica del Hospital Central de Valencia, de edades comprendidas entre 2 y 13 años; 60% correspondieron al sexo masculino; 85% tuvieron antecedente infeccioso reciente fundamentalmente en piel y 67% mostró evidencia indirecta de estreptococcia reciente con elevación del título de antiestreptolisinas "O". Se determinaron las concentraciones de las fracciones C3 y C4 del complemento sérico por inmunodifusión radial en forma longitudinal, durante la fase aguda del síndrome nefrítico y a la 5a y 10a semana de evolución; simultáneamente se estudió un grupo control (n-40). La fracción C3 se encontró muy deprimida durante la fase inicial del proceso en comparación con lo valores normales (p < 0.001), con recuperación de los valores a la 5a. y 10a. semana, pero sin alcanzar los níveles del grupo control (p < 0,05). Las concentraciones de C4 se encontraron estables en todas las fases estudiadas del Síndrome nefrítico, sin diferencia significativa con el grupo control (p < 0.05). Nuestros resultados sugieren consumo de C3 a expensas de la vía alterna del complemento, lo cual podría deberse a utilización de C3b en la solubilización de los complejos inmunes, aumento del catabolismo, disminución de la sintesis de C3 o fragmentación de C3 por la convertasa de C3 de la vía alterna, unida a la pared del capilar glomerular