Patrones morfológicos de la enfermedad glomerular en México: Reporte de un centro de referencia en nefropatología / Morphological patterns of glomerular disease in Mexico: Report of a reference center in nephropathology

RESUMEN Introducción: En México, la enfermedad renal crónica (ERC) representa un gran problema de salud y las glomerulopatías (GP) representan la tercera causa de ERC. Objetivo: Describir, desde una base de datos de biopsias renales (BR) nativas, los diferentes patrones morfológicos de GP en México. Métodos: Se analizaron registros de BR de riñón nativo en un centro de referencia en nefropatología, todas las BR fueron evaluadas por una única nefropatóloga (AVP). El diagnóstico final en cada caso se basó en parámetros clínicos e histopatológicos. Resultados: Fueron revisadas 2084 BR, con edad de 34.4 ± 17.6 años. 1085 BR (52.1%) en género femenino; el síndrome nefrótico fue más frecuente en hombres (p<0.001) y síndrome nefrítico fue más frecuente en mujeres (p<0.001). GP primarias y nefropatías túbulo-intersticiales fueron más diagnosticadas en hombres (p<0.01). Nefritis lúpica (NL) fue la GP secundaria más reportada. La glomeruloesclerosis focal y segmentaria (GEFS) fue la GP primaria diagnosticada con mayor frecuencia en ambos géneros. Vasculitis por inmunoglobulina A fue la enfermedad vascular más frecuentemente detectada. Síndrome nefrótico fue la indicación más frecuente de BR (42.9%), seguido de: síndrome nefrítico (23.9%), proteinuria aislada (16.4%), daño renal agudo (8.7%), alteraciones urinarias asintomáticas (6.2%) y ERC (1.8%). Conclusiones: La GP primarias con mayor frecuencia fueron GEFS. Las GP secundarias más frecuentemente reportadas fueron NL, predominantemente en mujeres. Se observó nefropatía IgA con mayor frecuencia en comparación con otras series publicadas en México. Hubo diferencias significativas en la presentación de GP en relación con el género y la edad del paciente.

ABSTRACT Introduction: In Mexico, chronic kidney disease (CKD) represents a major health problem, and glomerulopathies (GP) represent the third leading cause of CKD. Aim: From a database of native kidney biopsies (KB), describe the different morphological patterns of GP in Mexico. Methods: Records of native KB in a nephropathology referral center were evaluated by a single nephropathologist. The final diagnosis in each case was based on clinical parameters and histopathological findings. Results: 2084 KB were analyzed, patients were 34.4±17.6 years of age, there were 1085 KB (52.1%) in females; nephrotic syndrome was most frequent in males (p<0.001), and nephritic syndrome was more frequent in females (p <0.001). Primary GP and túbulo-interstitial diseases were most diagnosed in males (p <0.01). Lupus nephritis (LN) was the most-reported secondary GP. Focal and segmental glomerulosclerosis (FSGS) was the primary GP most often diagnosed in both genders. The most frequently detected vascular disease was immunoglobulin A vasculitis. Nephrotic syndrome was the most frequent indication for KB (42.9%), followed by: nephritic syndrome (23.9%), isolated proteinuria (16.4%), acute kidney injury (8.7%), asymptomatic urinary alterations (6.2%), and CKD (1.8%). Conclusions: The most frequently observed primary GP was FSGS, and LN was the most frequent secondary GP, predominantly in females, and IgA nephropathy was observed more frequently in comparison with other series published in Mexico. There were significant differences in GP presentation in relation to patient sex and age.

Glomerulopatía por C3: algoritmo diagnóstico en gestantes

La enfermedad glomerular comprende un grupo heterogéneo de entidades que se caracterizan por la pérdida de la arquitectura o función del glomérulo secundario a proceso inflamatorio del mismo de etiología autoinmune, infecciosa, paraneoplásica, que puede ser identificada con estudios de histopatología. Su reconocimiento durante la gestación representa un reto diagnóstico por la sobreposición de cambios fisiológicos, el debut de enfermedades autoinmunitarias o de enfermedades genéticas, entre otros. La presentación clínica suele encajar en grupos sindromáticos específicos, sin embargo, es frecuente que sean clínicamente indistinguibles o sobrepuestos. El debut de la enfermedad renal con curso clínico de rápida instauración y de evolución desfavorable con respecto a la función renal, hace mandatorio un estudio completo desde el abordaje clínico hasta la interpretación de los hallazgos histopatológicos, encaminado en la distinción de causas primarias y secundarias. Si bien las glomerulonefritis primarias no son las más frecuentes en la gestación, la identificación certera del diagnóstico y su adecuada clasificación permite el manejo dirigido y óptimo de las mismas. Se presentan los casos clínicos de dos gestantes con enfermedad glomerular primaria, con discrepancia en su diagnóstico, enfatizando en sus manifestaciones durante el curso de la gestación, el algoritmo diagnóstico utilizado, el tratamiento inicial y de mantenimiento utilizado. Se resalta la utilidad de la biopsia renal, específicamente la inmunofluorencia para aclarar el mismo.

Glomerular disease involves a heterogeneous group of entities that are characterized by loss of the architecture and function of the glomerulus and this can be caused by immunity, infectious and paraneoplastic etiologies. The aforementioned can be identified in histopathological studies. The recognition of this entity during pregnancy represents a diagnostic challenge due to the superposition of physiological changes, the development of autoimmune diseases and / or genetic disease, among others. Clinical manifestations can be into specific syndromic groups; however we can find indistinguishable manifestations and overlapping of this. When the disease is present its common to find rapidly establishment and unfavorable evolution about renal function. With this it's necessary to complete studies involving the initial clinical approach until histopathological findings with the goal to find primary and secondary causes. As it's known primary glomerulonephritis is not the most frequent in pregnancy, the accuracy in the diagnosis and the proper classification allows the direct and soon management. In this case report we describe 2 pregnant women with primary glomerular disease with discrepancy in their diagnosis. We talk about manifestations during pregnancy, the algorithm used in the diagnosis and finally the initial treatment and the maintenance used in these patients.

Evolution of glomerulopathies associated with rheumatoid arthritis / Evolución de las glomerulopatías asociadas a la artritis reumatoidea

Abstract Introduction: Rheumatoid arthritis is one of the most common clinical syndromes within rheumatological conditions and its association with glomerular diseases is rare. Objective: To describe the histopathological findings in renal biopsies in patients with rheumatoid arthritis and to correlate them with the clinical and laboratory manifestations at the beginning, at 6 months and at one year of follow-up. Patients and Methods: This is a retrospective observational study conducted in the Hospital de Clinicas "Jose De San Martin" in Buenos Aires, Argentina; Where we included 41 patients diagnosed with RA (ACR 1987) in a period of 20 years. Histopathological diagnoses of membranous nephropathy (MN), minimal change disease (MCD), secondary amyloidosis (AA), focal and segmental glomerulosclerosis (FSGS); mesangial glomerulopathy (MGP) and glomerulonephritis with extracapillary proliferation (GNEC) were included. Histopathological description, different treatments, years of evolution of rheumatoid arthritis Clinical and laboratory characteristics were analyzed during the first 6 months and one year of follow-up in order to determine the progression of renal failure calculated through the formula of MDRD of 4 variables (Modification of diet in renal disease) and the increase of proteinuria. Results: The most frequent histological finding was amyloidosis with 34,1 % (n=14), followed by mesangial glomerulopathy 21,9 % (n=9), membranous nephropathy 19,5 % (n=8), glomerulonephritis with extracapillary proliferation 12,1 % (n=5), focal and segmental glomerulosclerosis 7,3 % (n=3) and minimal change disease 8,2 % (n=2). Nephrotic syndrome was the most frequent presentation in patients with amyloidosis in 85,7 %, microhematuria occurred in 100 % of patients with MPG and in 80 % of patients with GNEC. In patients with AA, moderate to severe interstitial fibrosis occurred in 85,7 %, followed by GNEC and NM with 80 % and 40 % respectively. The 24-hour proteinuria, creatinine and glomerular filtration rate estimated by MDRD at 6 months and 12 months were evaluated. Concluding, that patients with AA, FSGS and GNEC had greater progression of renal failure at 12 months; the opposite occurred in patients with minimal change disease (MCD) and mesangial glomerulopathy (MGP) who had a lower progression of renal failure at one year of follow-up; There was a correlation in the glomerulopathies that had greater deterioration of the renal function had greater interstitial tubule involvement as was the case of amyloidosis. The glomerulopathies that presented greater proteinuria at the beginning were membranous nephropathy, amyloidosis and minimal change disease. Both membranous nephropathy and minimal change disease had partial remission at one year, in contrast to amyloidosis, which showed progression of proteinuria at 12 months of follow-up. Conclusion: The glomerulopathies that presented greater progression of renal failure at 1 year based on the estimation by MDRD 4, had a higher renal tubular interstitial involvement in renal biopsy and these were amyloidosis (AA), segmental focal glomerulosclerosis (FSGS), glomerulonephritis with proliferation extracapillary On the other hand, those with the best evolution in relation to the degree of proteinuria and the glomerular filtration rate determined by the MDRD4 equation were mesangial glomerulopathy, minimal change disease, and membranous nephropathy.

Resumen Introducción: La artritis reumatoidea (AR) es uno de los síndromes clínicos con mayor frecuencia dentro de las afecciones reumatológicas y su asociación con las enfermedades glomerulares es poco frecuente. Objetivo: Describir los hallazgos histopatológicos en las biopsias renales en pacientes con artritis reumatoidea y correlacionarlos con las manifestaciones clínicas y de laboratorio al inicio, a los 6 meses y al año de seguimiento. Pacientes y métodos: Es un estudio observacional retrospectivo realizado en un hospital Universitario en Buenos Aires, Argentina. Se incluyeron 41 pacientes con diagnóstico de artritis reumatoidea de acuerdo a los criterios establecidos por el Colegio Americano de Reumatología publicados en 1987; en un período de 20 años. Se incluyeron diagnósticos histopatológicos de nefropatía membranosa (NM), enfermedad de cambios mínimos (ECM), amiloidosis secundaria (AA), gloméruloesclerosis focal y segmentaria (GEFS); glomerulopatía mesangial (GPM) y glomerulonefritis con proliferación extracapilar (GNEC). Las características clínicas, de laboratorios, la descripción histopatológica, los años de evolución de la artritis reumatoidea y los diferentes tratamientos fueron analizados durante los primeros 6 meses y al año del seguimiento. Con esto, se buscó determinar la progresión de la insuficiencia renal, calculada a través de la fórmula de MDRD (Modification of Diet in Renal Disease) de 4 variables y el aumento de la proteinuria. Resultados: El hallazgo histológico más frecuente fue la amiloidosis, con un 34.1 % (n=14), seguido de la glomerulopatía mesangial (21,9 %, n=9), la nefropatía membranosa (19,5 %, n=8), la glomerulonefritis con proliferación extracapilar (12,1 %, n=5), la glomeruloesclerosis focal y segmentaria (7,3 %, n=3) y enfermedad de cambios mínimos (8,2 %, n=2). El síndrome nefrótico fue la forma de presentación más frecuente en los pacientes con amiloidosis (en un 85,7 % de los casos), la microhematuria se presentó en el 100 % de los pacientes con GPM y en el 80 % de los pacientes con GNEC. En el 85,7 % de los pacientes con AA, se presentó fibrosis intersticial moderada a severa, mientras que en la GNEC y la NM la fibrosis se observó en un 80 % y 40 % respectivamente. Se evaluó la proteinuria de 24 horas, la creatinina y la filtración glomerular estimada por MDRD a los 6 y a los 12 meses. Se concluyó que los pacientes con AA, GEFS y GNEC presentaron mayor progresión de la insuficiencia renal a los 12 meses. Lo contrario sucedió en los pacientes con enfermedad de cambios mínimos (ECM) y glomerulopatía mesangial (GPM), los cuales tenían una menor progresión de la insuficiencia renal al año de seguimiento. Hubo una correlación entre las glomerulopatías que tenían mayor deterioro de la función renal en las cuales se observó a su vez, mayor compromiso tubulointersti-cial, (este fue el caso de la amiloidosis). Las glomerulopatías que presentaban mayor proteinuria al inicio eran la nefropatía membranosa, la amiloidosis y la enfermedad de cambios mínimos. Tanto la nefropatía membranosa como la enfermedad de cambios mínimos, tenía remisión parcial tras un año, a diferencia de la amiloidosis, la cual presentaba progresión de la proteinuria a los 12 meses de seguimiento. Conclusión: Las glomerulopatías que presentaron mayor progresión de la insuficiencia renal al año, con base en la estimación por MDRD4, tenían en la biopsia renal mayor compromiso tubulointersticial. Estas fueron la amiloidosis secundaria, la glomeruloesclerosis focal y segmentaria, y glomerulonefritis con proliferación extracapilar. Por el contrario, las de mejor evolución respecto al grado de proteinuria y tasa de filtrado glomerular determinado por MDRD4, fueron la glomerulopatía mesangial, la enfermedad de cambios mínimos y la nefropatía membranosa.

Experiencia de 20 años en biopsia renal percutánea en adultos del Instituto de Nefrología / Twenty years of experience of the Nephrology Institute in performing percutaneous renal biopsy in adults

INTRODUCCIÓN: la biopsia renal percutánea constituye un elemento clave en el manejo de la enfermedad renal crónica, además de tener gran valor en la evaluación de la disfunción renal aguda y en el establecimiento de pronósticos. OBJETIVOS: conocer las indicaciones de la biopsia renal percutánea de riñones propios, en el Instituto de Nefrología entre 1988 y el 2007; las complicaciones relacionadas, los diagnósticos y su relación con la forma de presentación de la enfermedad renal a través de estudio descriptivo y transversal. MÉTODOS: los datos primarios para esta investigación fueron recolectados de la boleta de biopsia. Todas las biopsias renales durante los años de estudio fueron realizadas, siguiendo el protocolo del Departamento de Anatomía Patológica. La información fue procesada automatizada; paquete estadístico SPSS 22.0. Se utilizó análisis de distribución de frecuencias, promedio y desviación estándar en las variables cuantitativas y el test de independencia para identificar posibles relaciones entre variables. RESULTADOS: la edad media de los pacientes fue de 35,9 años. El 49,6 % eran hombres. Presentaron complicaciones 59 pacientes (3,9 %), fundamentalmente sangramientos. El síndrome nefrótico (47,0 %) y el síndrome nefrítico (11,2 %) fueron las indicaciones más comunes. Predominaron las enfermedades glomerulares (91,3 %) y dentro de estas las glomerulopatías primarias (75,3 %). Los diagnósticos más comunes fueron la glomeruloesclerosis segmentaria y focal (20,6 %) y la glomerulopatía proliferativa mesangial (16,8 %). CONCLUSIONES: la indicación más común de biopsia renal percutánea, es el síndrome nefrótico y la complicación más frecuente, el sangramiento. Los diagnósticos más usualmente realizados son: glomerulesclerosis segmentaria y focal, glomerulopatía proliferativa mesangial y nefritis lúpica.

INTRODUCTION: percutaneous renal biopsy is a key element in the management of the chronic kidney disease in addition to having great value in the evaluation of acute kidney dysfunction and in making prognoses. OBJECTIVE: to identify the indications for percutaneos renal biopsy of native kidney in the Nephrology Institute from 1988 to 2007; the related complications, the diagnoses and their relationship with the form of presentation of the renal disease through a descriptive cross-sectional study. METHODS: primary data for this research work were gathered from the biopsy form. All the renal biopsies performed during the study years followed the Pathological Anatomy Department protocol. The statistical package SPSS 22.0 was used for data processing. Frequency distribution analysis, averages and standard deviation were used in the quantitative variables whereas the independence test served to identify possible associations of variables. RESULTS: the average age of patients was 35.9 years. In the group, 49.6 % were men. Fifty nine patients presented (3.9 %) presented with complications, mainly bleeding. Nephrotic syndrome (47 %) and nephritic syndrome (11.2 %) were the most common indications for biopsy. Glomerular diseases (91.3 %) predominated and primary glomerulopathies prevailed among them (75.3 %). The most common diagnoses were focal and segmental glomerulosclerosis (20.6 %) and mesangial proliferative glomerulopathy (16.8 %). CONCLUSIONS: the most common indication of percutaneous renal biopsy is the nephrotic syndrome whereas the most frequent complication is bleeding. The usual diagnoses were focal and segmental glomerulosclerosis, mesangial proliferative glomerulopathy and lupus nephritis.

Characterization of a Trpc6 Transgenic Mouse Associated with Early Onset FSGS.

Rationale: Mutations in Transient Receptor Potential Channel 6 (TRPC6) gene are associated with autosomal dominant focal and segmental glomerulosclerosis (FSGS). The majority of the identified mutations affect the ion channel function. Since calcium channels are promising candidate drug targets, there is an an urgent need for a mouse model to assess new therapeutic drugs and to help delineate the pathogenic process leading to FSGS. We have previously reported the generation of three independent transgenic mouse lines carrying different Trpc6 mutations that display a glomerular disease comparable to the phenotype presented by individuals with FSGS. However, the utility of these models for drug testing is dampened by the late-onset of the presentation and the mild phenotypic manifestations. Methodology: In order to obtain a time-effective mouse model for Trpc6-associated FSGS we generated a new transgenic mutant Trpc6 mouse model emulating the amino acid change carried by the first pediatric patient of FSGS associated with a TRPC6 mutation: M132T. Results: Mice carrying the orthologous Trpc6 M131T transgene showed early onset proteinuria and early signs of FSGS. When exploring molecular consequences of the overexpression of this mutated form of Trpc6 in podocytes, differences in expression levels of Axin2 and β-catenin were found in glomeruli from transgenic Trpc6 M131T mice. These data supports the proposed molecular mechanisms related to the activation of calcineurin-NFAT/Wnt signaling, as outcome of the increased calcium influx caused by the mutated form of Trpc6. Conclusion: Given that the Trpc6 M131T mouse develops an early onset of FSGS-like phenotypes it represents a promising model for studying the pathogenesis of FSGS caused by TRPC6, facilitating the assessment of new drugs as treatments and allowing further studies to understand underlying molecular pathways involved in the development of the TRPC6 mediated disease.

Aspectos clínico epidemiológicos de la nefritis lúpica en pediatría. Estudio de 12 años / Clinical and epidemiological aspects of lupus nephritis in pediatrics: A 12 years study

Introducción: La Nefritis lúpica (NL) es una complicación frecuente del Lupus Eritematoso Sistémico en niños y adolescentes; comparado con pacientes adultos, los daños son más severos y la remisión menos frecuente. Objetivo principal: describir aspectos clínicos y epidemiológicos de la NL en pacientes atendidos en el Servicio de Nefrología del Hospital de Niños de Valencia. Métodos: Investigación de tipo cuantitativa, no experimental, descriptiva y retrospectiva. Resultados: Muestra: 21 pacientes, 13 adolescentes (62%), 15 hembras (71%); lesión histopatológica más frecuente: glomerulonefritis Difusa (Clase IV de la clasificación de la OMS); clínica predominante: edema, afecciones de piel y artritis; en la mayoría de los pacientes se evidenciaron alteraciones hematológicas, inmunológicas y del examen de orina. Se observó co-morbilidad asociada en un número importante de casos con afectación más frecuente del sistema nefrourológico y hematológico. Fallecieron 4 pacientes y hubo remisión de la sintomatología, de grado variable, en los otros casos, durante un periodo de seguimiento de 7 meses a 8 años (X:4.2±3.62). Conclusiones: La presente serie de NL muestra que se presenta más frecuentemente en adolescentes, del sexo femenino, con clínica predominantemente en piel y articulaciones; La glomerulonefritis difusa es la forma histológica más frecuente. El tratamiento fue diverso y la sobrevida global fue de 17 pacientes (71 %) durante un periodo de seguimiento de 4.2 años. La NL es una patología compleja en la edad pediátrica y su diagnóstico precoz, clasificación y manejo son importantes para el pronóstico.

Introduction: Lupus nephritis (LN) is a common complication of Systemic Lupus in children and adolescents; in these age groups, kidney damage is more aggressive, symptoms are more severe and remission is lower, compared with what occurs in adults. Methods: The objective was to describe clinical and epidemiological aspects of LN in patients attended at the Pediatric Nephrology Service, Children’s Hospital of Valencia - Venezuela. The investigation was quantitative, not experimental, descriptive and retrospective. Results: 21 patients, 13 adolescents (62%), 15 female (71%). Diffuse Glomerulonephritis (Class IV Lupus Nephritis of WHO classification) was the most frequent lesion; clinical manifestations at presentation were edema, skin lesions and arthritis. Other manifestations: blood disorders, immune and urine alterations on admission. Co-morbidity associated was more frequent in the nephrourological and hematological systems. 4 patients died and remission of symptoms, of variable degree, was seen in the other cases. Conclusions: This series of LN in pediatrics shows that it is more frequent in female adolescents with clinical manifestations in skin and joints. The most frequent lesion is diffuse glomerulonephritis. Treatment was variable and the total survival of patients was 71% (17 patients) during a follow up of approximately 4.2 years. Lupus nephritis is a complex pathology in pediatric ages and its early diagnosis, proper histopathologic classification and adequate therapeutic management are important in terms of quality of life, prognosis and survival of patients.

Glomerulopatia colapsante / Collapsing glomerulopathy

Background: Collapsing glomerulopathy is a cause of nephrotic syndrome with massive proteinuria secondary to podocyte proliferation and glomerular collapse. It is characterized by an almost inevitable progression to end stage renal failure, poor response to treatment and high post-transplant recurrence. Its frequency has increased in recent years due to its common association with Human Immunodeficiency Virus (HIV) infection and the growing recognition of new etiologic agents such as drugs and parvovirus B19. Therefore, it is a disease of growing interest for clinicians. The aim of this review is to update the clinical presentation, diagnosis, pathogenesis and therapeutic alternatives of this disease.

Prevalencia de enfermedad renal en pacientes adolescentes internados en el Servicio de Nefrología del Hospital de Niños Dr. Ricardo Gutierrez / Prevalence of renal disease in adolescents patients treated in Nephrology Unit of Children´s Hospital Dr. Ricardo Gutierrez

Introducción: Los pacientes adolescentes representan un desafío para el nefrólogo. Aunque la patología renal del mismo se asemeja más a la del adulto, tiene una epidemiología única a considerar. Métodos: Estudio descriptivo, retrospectivo. Se relevaron 43 historias clínicas de pacientes entre 10 Y 18 anos ingresados por primera vez en nefrología entre enero de 2009 y mayo de 2011, analizando datos demográficos, motivo de consulta, lugar de referencia, tiempo entre inicio de síntomas y la referencia al servicio, días de internación, diagnóstico de enfermedad renal y causas de ingreso a diálisis. Resultados: Se internaron 394 pacientes, 136 fueron adolescentes. 43 internaciones de primera vez, y de estos, 24 mujeres. Edad promedio 13,5 años ± 2,37. 27 pacientes de provincia de Bs. As., 11 CABA, y 5 resto del País. 27 derivados desde nuestro propio hospital y 16 de otros centros médicos. Los síntomas y signos más frecuentes fueron hematuria, edemas, proteinuria y disminución del filtrado glornerular. La media entre inido de síntomas y la consulta fue 15 días (rango 1-30). Promedio de días de internación 13,7 (rango 2-95). Las patologías prevalentes fueron las glomerulopatias y la nefropatía lúpica la enfermedad renal más frecuente. 11 pacientes requirieron diálisis, y 9 permanentemente. Conclusiones: Los adolescentes presentan prevalencia patológica diferente a la de pediatría. La presencia de IRCT sin diagnóstico previo fue significativa.

Introduction: Teenager patients represent a challenge for Nephrologists. Although renal pathology of such patients is similar to adults, it has a unique epidemiology which must be considered. Methods: Retrospective, descriptive study. 43 clinical histories of patients between 10 and 18 years old admitted for the first time in Nephrology division between January 2009 and May 2011 were reported. We analyzed demographic data, consultation cause, reference place, time between the beginning of symptoms and the reference to the division, days of hospitalization, renal disease diagnosis and dialysis admission causes. Results: 394 patients were admitted, 136 were teenagers, 43 admissions for the first time and from these 24 women. Average age 13,5 years old +-2,37.27 patients from Buenos Aires province, 11 Capital City of Buenos Aires and 5 from the rest of the country. 27 referred from our own hospital and 16 from other medical centers. The 139 most frequent symptoms and signs were hematuria, edema, proteinuria and decrease of glomerular filtration. The average between the beginning of symptoms and consultation was 15 days (range1-30). Admission day average 13,7(range 2-95). Prevalent pathologies were glomerulopathies and lupic nephropathy the most frequent renal disease. 11 patients required dialysis. Conclusions: Teenagers show different pathological evidence in comparison to pediatrics. The presence of IRCT without previous diagnosis was significant.

Glomerulopatias prevalentes na Bahia, um estudo baseado em biópsias / Glomerulopathies prevalent in Bahia, a study based on biopsies

A prevalência de doenças renais em pacientes encaminhados aos Serviços de Nefrologia em hospitais terciários em Salvador, Brasil, foi avaliada através de exames histopatológicos. Analisamos, retrospectivamente, 228 biópsias renais realizadas entre janeiro de 2003 a junho de 2006. Destes, 159 preencheram os critérios para inclusão no estudo. Foram examinados por microscopia óptica, imunofluorescência (arquivos de imagens digitais) e, quando necessário, por microscopia eletrônica. Compilamos informações sobre gênero, idade, etnicidade, a síndrome clínica e a duração da doença renal. A revisão histológica das biópsias foi realizada em três etapas. Inicialmente, por dois patologistas, simultaneamente, usando um microscópio multiobservador. Em seguida, os diagnósticos foram revistos por um observador independente. Ao final, os casos sem unanimidade no diagnóstico foram revistos pelos três patologistas em conjunto, para se chegar a um diagnóstico consensual. A nefropatia primária mais freqüente foi a esclerose glomerular focal e segmentar, somando 27% dos casos. Outros 15% foram identificados como parte do espectro alteração mínima-esclerose segmentar focal desta doença. Encontramos glomerulopatia membranosa em 9%, glomerulonefrite membranoproliferativa em 7%, e nefropatia por imunoglobulina A em 5%. A nefropatia secundaria mais freqüente foi a nefrite lúpica, constituindo 14% do total. Concordância entre observadores no diagnóstico das nefropatias foi de 93%, com kapa 0,919, DP 0,03 e p<0,01. Este é o primeiro estudo descritivo da prevalência das glomerulopatias em Salvador, Brasil, com utilização de imunofluorescência e microscopia eletrônica. As glomerulopatias primárias e secundárias mais freqüentes foram glomeruloesclerose focal e segmentar e nefrite lúpica. Estes achados representam uma alteração da prevalência das glomerulopatias na Bahia, antes mais influenciada pela infestação por Schistosoma mansoni.

The prevalence of renal diseases in patients referred to tertiary hospitals in Salvador, Brazil was evaluated by histopathological examination. 228 biopsies of native kidneys, performed from January, 2003 through June, 2006, were retrospectively analyzed; 159 of these fulfilled the criteria for inclusion in this study. They were reviewed by light microscopy, immunofluorescence (digital image archives) and, whenever necessary, by electron microscopy. Gender, age ethnicity, duration of the renal disease and clinical syndrome were studied. Histological revision of the biopsies was performed in three rounds: 1st, by two pathologists using a multiobserver microscopy; 2nd, an independent revision by an external examiner and 3rd, the cases given discrepant diagnosis were revised by all the observers working together. Focal and segmental glomerular sclerosis was the most frequent primary nephropathy, encountered in 27% of the cases. Another 15% were identified as part of the minimal change - focal segmental sclerosis spectrum of disease. Membranous glomerulopathy comprised 9%, membranoproliferative glomerulonephritis 7%, and immunoglobulin A nephropathy, 5% of the total. Lupus nephritis was the most common secondary nephropathy, corresponding to 14% of the cases. Interobserver concordance in the diagnosis of nephropathies was 93%, with Kappa 0.919, standard error 0.03 and P < 0.01. This is the first descriptive study of the prevalence of glomerulopathies in renal biopsies in Salvador, Brazil, using all the recourses of immunofluorescence and electron microscopy. Focal and segmental glomerulosclerosis and systemic lupus nephritis were identified as the most frequent primary and secondary glomerulopathies, respectively. This data may represent a shift in the patter of distribution of glomerulopaties in Bahia, formerly influenced by S. mansoni infection.

Síndrome nefrótica primária em adultos / Primary nephrotic syndrome in adults

O conceito e os critérios clínicos e laboratoriais para o diagnóstico da Síndrome Nefrótica (SN) são revisados neste artigo, assim como a definição de resposta ao seu tratamento. São abordadas as glomerulopatias de causa primariamente renal, particularmente o seu tratamento e prognóstico. Na fase inicial da SN a abordagem está centrada no diagnóstico e tratamento das complicações do estado nefrótico, muitas vezes graves e independentes da etiologia da SN, além da utilização de “medidas gerais” como restrição de sal, uso judicioso de diuréticos e de inibidores da enzima conversora e/ou bloqueadores do receptor da angiotensina. Procede-se o diagnóstico etiológico da doença, se de causa primária ou secundária. Nas glomerulopatias primárias, esse diagnóstico necessariamente dependerá da biópsia renal, a qual definirá qual o protocolo de “tratamento específico” de um ou mais imunossupressores a ser prescrito. Uma proporção significativa de pacientes pode não responder ao tratamento e permanecer com o estado nefrótico, e a decisão por “medidas gerais” e de nefroproteção em geral é a conduta mais adequada, pela baixa probabilidade de resposta e alto potencial de efeitos colaterais dos imunossupressores a longo prazo, como os corticosteróides, agentes citotóxicos e/ou inibidores da calcineurina. Futuramente o uso de drogas mais eficientes e com menos efeitos colaterais poderá ampliar as possibilidades de tratamento específico das glomerulopatias primárias.

Clinical and laboratorial criteria for the definition of Nephrotic Syndrome (NS) are reviewed in this article, as well as characterization of response to its treatment. Primary glomerulopathies are specifically described, particularly their treatment and prognosis. In the initial phase of NS, the approach is mainly focused in the diagnosis and treatment of complications of the nephrotic state, many times severe and independent of the etiology of NS, when general measures such as salt restriction, judicious use of diuretics and angiotensin-enzyme inhibitors and/or angiotensin-receptor blockers are prescribed. Then the etiology of NS is determined, if associated to a primary or a secondary cause. In primary glomerulopathies, this diagnosis relies on renal biopsy that will define a specific immunosuppressive protocol to be prescribed. A significative proportion of these patients could not respond to treatment and remain nephrotic, when to keep general measures and nephroprotection should be the best approach, because immunosuppressors such as corticosteroids, cytotoxic agents and calcineurin inhibitors have a small probability of response and high potential for toxicity in the long term. In the future, more efficient drugs with less side-effects should broaden the options of specific treatments for primary glomerulopathies.

Biopsia renal en pediatría: análisis de la casuística de 28 años: Hospital de Niños de Valencia-Venezuela: [revisión] / Renal biopsy in pediatrics: casuistica analysis of 28 years: Hospital of Niños of Valencia-Venezuela: [review]

El análisis de los resultados de casuísticas de biopsias renales es importante con fines diagnósticos, terapéuticos y de pronóstico. Evaluar la serie de biopsias renales en el Hospital de Niños de Valencia, Venezuela, durante el período 1978-2007. Fueron analizadas 421 biopsias renales practicadas en 395 pacientes, de 2 meses a 20 años, 57% varones. El material fue procesado por microscopía óptica, inmunofluorescencia y microscopía electrónica en 98% de los casos. Se obtuvo muestra adecuada (más de 10 glomérulos) en 93% de los casos (n=392). Indicaciones clínicas: síndrome nefrótico 199(50%), síndrome nefrítico atípico 53(13%), otro: (hematuria/proteinuria, proteinuria, trasplante, enfermedades sistémicas 143(37%). Resultados Histopatológicos: A.-Glomerulonefrítis primaria (GNP) 302 casos (77%), B.-Nefropatías secundarias (NS) 68 casos (17%), C.-Riñones trasplantados 28 casos (7%).-Diagnósticos en GNP: 1) Lesión de cambios mínimos 140(46%), 2) Glomeruloesclerosis segmentaria y focal 79 (26%), 3) GN proliferativa y/o mesangial 67(22%), 4) GN Membranosa 16 (5%). -Diagnósticos en NS: Nefritis lúpica: 20 casos (32.25%), Nefropatía IgA: 22 casos (35.50%); Otras: 20 casos (32.25%). -Diagnósticos en riñones trasplantados: rechazo agudo 50%, necrosis tubular aguda 25%, rechazo crónico 20%, enfermedad recurrente en trasplante 5%. Complicaciones: Hematuria transitoria: 21 casos (5%), hematoma perirenal: 3(<1%), perforación intestinal: 2 (<0.5%), hemorragia importante: 2 (<0.5%), nefrectomía: 1(0.2%). La presente es una de las primeras casuísticas de biopsias renales reportadas en Latinoamérica y una de las más grandes en el mundo y, de acuerdo a nuestros resultados, es un procedimiento seguro con gran utilidad diagnóstica, pocas complicaciones, sin mortalidad.

Evaluation and analysis of the results of renal biopsy are important for diagnostic, therapeutic and prognostic matters. To evaluate a series of renal biopsies performed during the period 1978-2007 in the Hospital de Niños de Valencia, Venezuela. All patients had history of either primary or secondary nephropathies. 421 biopsies were done in 377 patients, ages 2 months-20 years; 57% boys. 26 patients were re-biopsed. Percutaneous needle biopsy (PNB) was performed in all the patients, except in one who underwent open biopsy because of a solitary kidney. Renal tissue was processed for optical, inmunofluorescence and electronic microscopy in 98% of cases. The biopsy technique, clinical syndromes at presentation, hystopathological pattern, effectiveness and complications are described. Adequate sample was obtained in 392 cases (93%) (more than 10 glomeruli) and inadequate or failed biopsy in 29(7%). Clinical syndromes at presentation were: nephrotic syndrome: 199 cases (50%), atypical acute nephritic syndrome: 53 (13%), others: hematuria and proteinuria, isolated proteinuria, kidney transplant biopsy or systemic diseases: 143(37%). The hystopathological pattern obtained was as follows. A.-Primary glomerulonephritis (PG): 302 cases, 77%, B.-Secondary nephropathies: 68 cases, 17%, C.- Kidney transplant biopsies: 28 cases, 5 %. Primary Glomerulonephritis diagnosis: minimal change disease: 140 cases, 46%, Focal Segmental Glomerulosclerosis: 79(26%), diffuse proliferative glomerulonephritis/mesangial: 67(22%), membranous glomerulonephritis: 16(5%). Secondary nephropathies: lupus nephritis: 20 cases (32.25%), IgA Nephropathy: 22 cases (35.50%), others: 20 cases (32.25%).Transplant biopsies: rejection 50%, acute tubular necrosis 25%, chronic rejection 20%, and recurrent disease 5%. Complications: transient hematuria: 21(5%), perirenal hematoma: 3(<1%), gut perforation (<0.2%), bleeding which required blood transfusion: 2(<0.5%) and nephrectomy because of incontrollable...

Estudo das doenças glomerulares em pacientes internados no Hospital Geral César Cals (Fortaleza-CE) / Study of glomerular diseases in patients admitted to the Hospital Geral César Cals (Fortaleza-CE)

A biópsia renal percutânea constitui o padrão-ouro para o diagnóstico, prognóstico e tratamento das doenças glomerulares. Estudamos 51 pacientes que foram submetidos à biópsia renal no Hospital Geral César Cals, em fortaleza, Ceará Brasil, no período de janeiro de 2000 a dezembro de 2007. Houve predomínio do sexo feminino (57%). A faixa etária mais afetada foi de 20-40 anos. A principal forma de apresentação das glomerulopatias foi a síndrome nefrótica (49%), e o padrão histopatológico mais prevalente nas glomerulopatias secundárias (37%). Tivemos 5,8% de complicações atribuídas à biópsia renal, tendo sido a hematúria macroscópica a principal responsável (3,9%). Estudos mais abrangentes são necessários para traçar o perfil epidemiológico das doenças glomerulares no Estado do Ceará.

A percutaneous renal biopsy is the gold standard for diagnosis, prognosis and treatment of glomerular diseases. We studied 51 patients who underwent renal biopsy at the Hospital Geral César Cals, Fortaleza, Ceara, Brazil, from January 2000 to December 2007. There was predominance of females (57%). The most affected age group was 20-40 years. The main form of presentation was nephrotic syndrome glomerulopathies (49%), and histopathological pattern more prevalent in secondary glomerulopathies (37%). 5.8% had complications attributed to renal biopsy, macroscopic hematuria was the main cause (3.9%). Large studies are needed to delineate the epidemiological profile of glomerular diseases in Ceará.

Glomerulopatías en el Paraguay. Reporte del registro de biopsias renales en 1072 casos / Glomerulopathies in Paraguay. Report of registry of renal biopsies in 1072 cases

La biopsia renal es el principal método de diagnóstico de las glomerulopatías. El Registro de biopsias renales es importante para conocer la situación epidemiológica y clínico­patológica de las enfermedades renales de un país y las variaciones geográficas entre los países o continentes. Para conocer la situación actual de las glomerulopatías del Paraguay se ha realizado el presente estudio en 1.365 biopsias renales registradas entre agosto de 1989 a junio de 2005 en el Departamento de Patología del IICS, que es el Centro de Referencia y Registro de Biopsias Renales del país, analizando sus aspectos histológicos, demográficos y las diferencias entre periodos quinquenales de estudio. Del total de casos, 1072 (75.5%) fueron glomerulopatías y, a diferencia de la mayoría de los países, se observó un predominio de glomerulonefritis secundarias (GNS) (57.3%) de las cuales 85.9% fueron nefritis lúpica (NL). En las glomerulonefritis primarias (GNP) la GN proliferativa mesangial (GNPM) y la membranoproliferativa (GNMP) fueron las mas frecuentes (39.8% y 28.2%), mientras que la Nefropatía por IgA (NIgA) y la Enfermedad de cambios mínimos (ECM) fueron raras (1.9% y 1.3%). No se observaron cambios significativos de incremento o disminución de tipos histológicos a través de los periodos de estudio tanto en las GNP como en las GNS. La existencia de este registro de biopsias renales fue la base para la creación del Registro de Glomerulopatías del Paraguay en el año 2004, cuyos datos son necesarios para establecer programas de tratamiento y prevención de las enfermedades glomerulares en nuestro país a fin de disminuir su progresión al estadío terminal.

Renal biopsy is the main diagnostic method of glomerulopathies. The registry of renal biopsies is important to know the epidemiological and clinical and pathological situation of renal diseases of a country and the geographic variations between countries or continents. In order to know the current situation of glomerulopathies in our country, we studied 1,365 renal biopsies registered between August 1989 to June 2005 at the Pathology Department of the IICS, the reference center and the Renal Biopsy Registry of the country, analyzing histological and demographic aspects as well as the differences between five­year periods of study. On the total cases, 1,072 (75.5%) were glomerulopathies while secondary glomerulonephritis (SGN) were more frequent (57.3 %) with 85.9% of lupus nephritis (LN) in contrast to most countries. Among primary glomerulonephritis (PGN), mesangioproliferative GN (MPGN) and membranoproliferative GN (MPGN) were predominant (39.8% and 28.2%) while IgA Nephropathy (IgAN) and Minimal Change Disease (ECM) were rare (1.9% and 1.3%). We did not observe significant changes of increases or decreases of histological types through the study periods in PGN as well as in SGN. The existence of this registry of renal biopsy was the base for the creation of the Paraguayan Registry of Glomerulopathies in 2004, which data are necessary to establish treatment and prevention programs of glomerular diseases in our country in order to decrease their progression to end­stage renal disease.

Creación del registro de Glomerulopatias del Paraguay / Creation of the Paraguayan registry of Glomerulopathies

La glomerulonefritis crónica es una de las causas principales de enfermedades renales en estadío terminal (ERET) en países en vías de desarrollo, con incremento de su incidencia y prevalencia. En este estadío solamente sobreviven los pacientes con posibilidades de acceso a la terapia de reemplazo renal (TRR) como la diálisis y el transplante renal, por su costo elevado, mientras que aquellos con enfermedades renales crónicas (ERC), con ingresos bajos y sin cobertura de seguro de salud, pueden progresar a ERET y fallecer por uremia, porque la TRR no es accesible para ellos. En el Paraguay un gran número de pacientes no tienen acceso a TRR y no existen datos nacionales sobre enfermedades renales para desarrollar programas de prevención y tratamiento. Para conocer la situación real de ERC en nuestro país, el primer paso fue la creación del Registro de Glomerulopatías del Paraguay, en septiembre de 2004, por Resolución de Ministerio de Salud Pública y Bienestar Social basado en el Registro de Biopsias renales del IICS de la Universidad Nacional de Asunción, que es el Centro de Referencia de biopsias renales del país. Este Registro nos proveerá de datos de incidencia, prevalencia, tipos, aspectos epidemiológicos y clínicopatológicos de las enfermedades renales y también nos permitirá realizar estudios epidemiológicos comparativos con otros Registros del mundo. La creación del Registro será un importante apoyo para implantar programas de diagnóstico precoz, prevención y tratamiento de las glomerulopatía a fin de disminuir la gran carga de ERET en pacientes renales y también en el aspecto financiero del país.

Chronic glomerulonephritis is one of the main causes of end­stage renal diseases (ESRD) in developing countries with increasing incidence and prevalence rates. In this stage, because of the high costs only patients with financial possibility that have access to renal replacement therapy (RRT) such as dialysis or renal transplant are alive; while people with chronic renal diseases (CRD), low income and without coverage of health insurance can progress to ESRD and death from uremia because RRT is out of their reach. In Paraguay, a large number of patients with CRD are not able to access to RRT and there is not a national data on renal disease to develop prevention and treatment programs of renal diseases. The first step to know the real situation of CRD was the creation of the Paraguayan Registry of Glomerulopathy on September 2004 by Resolution of the Ministry of Public Health based on the Renal Biopsy Registry of IICS of the National University of Asunción, the reference center of renal biopsy of the country. This National Registry of Glomerulopathies will provide us data about incidence, prevalence, types, epidemiological, clinical and pathological aspects of renal diseases and will also allow to carry out epidemiological studies in comparison with other registries of the world. The creation of the registry will be an important support to implement programs of early diagnosis, prevention and treatment of glomerulopathies in order to decrease the great burden of the ESRD on renal patients and also on the financial possibilities of the country.