A rare case of PLA2R- and THSD7A-positive idiopathic membranous nephropathy / Positividade tecidual dupla para PLA2R e THSD7A em nefropatia membranosa idiopática: raro relato de caso

ABSTRACT Idiopathic membranous nephropathy (IMN) is a frequent cause of nephrotic syndrome in adults. In terms of etiology, the condition may be categorized as primary/idiopathic or secondary. Literature on the pathophysiology of IMN has indicated the presence of autoantibodies (PLA2R and THSD7A) directed against podocyte antigens. The detection of antibodies against a domain favors IMN. The presence of autoantibodies against one of the domains would in theory exclude the possibility of there being autoantibodies against the other domain. However, cases of patients with PLA2R- and THSD7A-positive disease have been recently reported, showing that antibodies against two targets may be concomitantly produced via yet unknown pathophysiological mechanisms. This study reports the case of a 46-year-old male patient with nephrotic-range proteinuria, hematuria, hypoalbuminemia, and hypercholesterolemia submitted to biopsy and histopathology examination (LM, IF, IHC, and EM) eventually diagnosed with PLA2R- and THSD7A-positive IMN associated with IgA nephropathy, stressing our experience with the use of IgG subclasses, PLA2R, and THSD7A in the workup for MN and the relevance of adopting a broad and adequate approach to elucidating and acquiring knowledge of the pathophysiology of IMN.

RESUMO A Nefropatia Membranosa Idiopática (NMi) é uma frequente causa de síndrome nefrótica em adultos e sua etiologia pode ser estratificada em primária/idiopática ou secundária. O conhecimento da fisiopatologia da NMi sugeriu a presença de autoanticorpos (PLA2R e a THSD7A) direcionados contra antígenos existentes nos podócitos. A detecção de anticorpos contra um domínio favorece NMi. A presença de autoanticorpos contra um desses domínios autoexcluiria a possibilidade de autoanticorpos contra o outro domínio; no entanto, recentemente foram descritos casos que apresentaram dupla positividade para PLA2R e THSD7A, comprovando que, por mecanismos fisiopatológicos ainda não conhecidos, raramente pode existir produção concomitante de anticorpos contra os dois alvos. O presente estudo tem por objetivo relatar o caso de um paciente de 46 anos de idade, do sexo masculino, que apresentou quadro de proteinúria nefrótica, hematúria, hipoalbuminemia e hipercolesterolemia submetido a biópsia e exame histopatológico (ML, IF, IHQ e ME), confirmando um caso raro de NMi com positividade dupla para os anticorpos anti-PLA2R e anti-THSD7A e associação à nefropatia por IgA, mostrando nossa experiência com a utilização de subclasses de IgG, PLA2R e THSD7A na rotina laboratorial para a investigação da GNM e enfatizando a importância de uma abordagem ampla para adequada elucidação e conhecimento dos mecanismos fisiopatológicos na NMi.

Anca negative pauci-immune crescentic glomerulonephritis and mixed connective tissue disease: a case study / Glomerulonefrite crescêntica pauci-imune ANCA-negativa e doença mista do tecido conjuntivo: relato de um caso

Abstract One of the most common causes of rapidly progressive glomerulonephritis (RPGN) is pauci-immune crescentic glomerulonephritis (CrGN). In the majority of cases, this condition has a positive serologic marker, the anti-neutrophil cytoplasmic antibodies (ANCAs), but in approximately 10% there are no circulating ANCAs, and this subgroup has been known as the ANCA-negative pauci-immune CrGN. RPGN can be associated with systemic diseases, but there are only few case reports describing the association with mixed connective tissue disease (MCTD). The authors report a case of ANCA-negative CrGN associated with a MCTD.

Resumo Uma das causas mais comuns da glomerulonefrite rapidamente progressiva (GNRP) é a glomerulonefrite crescêntica (GNC) pauci-imune. Na maioria dos casos, a patologia apresenta um marcador sorológico positivo, o anticorpo anticitoplasma de neutrófilos (ANCA), mas em cerca de 10% dos pacientes não há ANCAs circulantes, perfazendo um subgrupo da patologia conhecido como GNC pauci-imune ANCA-negativa. A GNRP pode estar associada a doenças sistêmicas, mas são poucos os relatos de caso que descrevem sua associação com doença mista do tecido conjuntivo (DMTC). O presente artigo relata um caso de GNC ANCA-negativa associada a DMTC.

Renal histological alterations induced by acute exposure of titanium dioxide nanoparticles / Alteraciones histológicas renales inducidas por la exposición aguda de nanopartículas de dióxido de titanio

SUMMARY: Titanium dioxide nanoparticles (TiO2 NPs) are widely used in many commercial products, nanomedicine, agriculture, personal care products, different industries and pharmaceutical preparations with potential risk in human health and the environment. The current work was conducted to investigate the renal damage that might be induced by the acute toxicity TiO2 NPs. A total of 40 healthy male adult Wistar albino rats (Rattus norvegicus) were exposed to TiO2 NPs (126, 252, 378 mg/kg bw) for 24 and 48 h. Fresh portions of the kidneys from each rat were processed for histological and histochemical alterations. In comparison with respective control rats, exposure to TiO2 NPs has marked the following glomerular, tubular and interstitial alterations including the followings: glomerular congestion, Bowman's capsule swelling and dilatation, inflamed glomeruli, renal tubules cloudy swelling, karyorrhexis, karyolysis, infiltration of inflammatory cells, congestion, necrosis, hydropic degeneration, dilatation and congestion of blood vessels, hyaline droplets and hyaline casts precipitation, interstitial edema and fibrosis. From the findings of the current work one may conclude that TiO2 NPs are capable of inducing kidney damage with more insulation in the cortex and the proximal convoluted tubules than the medulla and the distal ones respectively. In addition, it might be concluded that renal damage induced by these nanomaterials is dose and duration of exposure dependent. Further hematological, biochemical, immunohistochemical, and ultra-structural studies are recommended.

RESUMEN: Las nanopartículas de dióxido de titanio (TiO2 NP) se usan ampliamente en muchos productos comerciales, nanomedicina, agricultura, productos para el cuidado personal, diferentes industrias y preparaciones farmacéuticas con riesgo potencial para la salud humana y el medio ambiente. El trabajo actual se realizó para investigar el daño renal que podría ser inducido por la toxicidad aguda NP de TiO2. Un total de 40 ratas Wistar albinas adultas sanas (Rattus norvegicus) fueron expuestas a TiO2 NP (126, 252, 378 mg / kg de peso corporal) durante 24 y 48 h. Las muestras de los riñones de las ratas se procesaron para estudios histológicos e histoquímicos. En comparación con las ratas control, la exposición de las ratas a TiO2 NP presentaron las siguientes alteraciones glomerulares, tubulares e intersticiales: congestión glomerular, dilatación de la cápsula de Bowman, inflamación glomerular, túbulos renales aumentados, cariorrexis, cariólisis, infiltración de células inflamatorias, congestión, necrosis, degeneración hidrópica, dilatación y congestión de vasos sanguíneos, gotas y precipitaciones hialina, edema intersticial y fibrosis. A partir de los hallazgos del trabajo actual, se puede concluir que las NP de TiO 2 son capaces de inducir daño renal con más aislamiento en la corteza y en los túbulos contorneados proximales que en la médula y los túbulos contorneados distales, respectivamente. Además, se podría concluir que el daño renal inducido por estos nanomateriales depende de la dosis y la duración de la exposición. Se recomiendan estudios adicionales hematológicos, bioquímicos, inmunohistoquímicos y ultraestructurales.

Most common histopathological patterns of the Minas Gerais Association of the Centers of Nephrology

SUMMARY INTRODUCTION: We analyzed the distribution and frequency of glomerular diseases in patients biopsied between 1992 and 2016 in centers that make up the AMICEN (Minas Gerais Association of Nephrology Centers). METHODS: We analyzed the biopsy reports of patients from 9 AMICEN nephrology centers. We took note of their age, gender, ultrasound use, post-biopsy resting time, whether the kidney was native or a graft, number of glomeruli and indication for the biopsy. The kidney biopsy findings were broken down into four categories: glomerular and non-glomerular diseases, normal kidneys and insufficient material for analysis. Those patients diagnosed with glomerular diseases were further divided into having primary or secondary glomerular diseases. RESULTS: We obtained 582 biopsy reports. The median age was 38 years (1 to 85). The number of glomeruli varied between 0 and 70 (median = 13.0). In total, 97.8% of the biopsies were ultrasound guided. The main indication was nephrotic syndrome (36.9%), followed by hematuria-proteinuria association (16.2%). Primary glomerular diseases proved to be the most frequent (75.3%), followed by secondary diseases (24.7%). Among the primary glomerular diseases, FSGS was found at a higher frequency (28.8%), while among the secondary diseases, SLE was the most prevalent (42.4%). Regarding prevalence findings, those for both primary and secondary diseases were similar to those found in the large Brazilian registries published thus far. CONCLUSION: Glomerular disease registries are an important tool to identify the prevalence of such disease in regions of interest and can serve as an instrument to guide public policy decisions concerning the prevention of terminal kidney diseases.

RESUMO INTRODUÇÃO: Analisamos a distribuição e frequência de doenças glomerulares de pacientes biopsiados entre 1992 e 2016 em centros que compõem a Amicen (Associação de Minas Gerais de Nefrologia). MÉTODOS: Analisamos os relatórios de biópsia de pacientes de nove centros de nefrologia da Amicen. Observamos idade, gênero, uso de ultrassom, tempo de descanso pós-biópsia, se o rim era nativo ou um enxerto, número de glomérulos e indicação para a biópsia. Os achados da biópsia do rim foram divididos em quatro categorias: doenças glomerulares e não glomerulares, rins normais e material insuficiente para análise. Os pacientes diagnosticados com doenças glomerulares foram ainda divididos em doenças glomerulares primárias ou secundárias. RESULTADOS: Obtivemos 582 relatórios de biópsia. A idade mediana foi de 38 anos (1 a 85). O número de glomérulos variou entre zero e 70 (mediana = 13,0). No total, 97,8% das biópsias foram guiadas por ultrassom. A principal indicação foi síndrome nefrótica (36,9%), seguida de associação hematúria-proteinúria (16,2%). As doenças glomerulares primárias revelaram-se as mais frequentes (75,3%), seguidas de doenças secundárias (24,7%). Entre as doenças glomerulares primárias, o FSGS foi encontrado em maior frequência (28,8%), enquanto nas doenças secundárias, o lúpus eritematoso sistêmico foi o mais prevalente (42,4%). Quanto aos achados de prevalência, aqueles para doenças primárias e secundárias foram semelhantes aos encontrados nos grandes registros brasileiros publicados até o momento. CONCLUSÃO: Os registros de doenças glomerulares são uma ferramenta importante para identificar a prevalência dessas doenças em regiões de interesse e pode servir como um instrumento para orientar decisões de políticas públicas relativas à prevenção de doenças renais terminais.

Recurrencia de Síndrome de Goodpasture con negativización de anticuerpos anti-membrana basal glomerular: caso clínico / Recurrence of goodpasture syndrome with negative antiglomerular basement antibodies: report of one case

Goodpasture Syndrome is described as a single episode disease entity. It is diagnosed with the demonstration of antiglomerular basement (anti-GBM) antibodies in plasma or renal tissue. Although the recurrence of anti-GBM disease is rare, it has been reported in up to 3% of cases. Recurrence with negative anti-GBM antibodies in plasma is even less frequent We report a 63 years old male in whom anti-GBM disease recurred without detectable anti-GBM antibodies in plasma, despite having positive antibodies at the onset.

Smoking-Related Renal Histologic Injury in IgA Nephropathy Patients

PURPOSE: Smoking reportedly exerts deleterious effects on renal function; however, its effects on histology have not been clarified in patients with IgA nephropathy (IgAN). MATERIALS AND METHODS: Renal histology was evaluated in a cohort of 397 patients diagnosed with IgAN according to smoking status and dose in relation to renal function. RESULTS: Among the study cohort, which was predominantly male (88.5%), 52 patients (13%) were current smokers. These current smokers demonstrated more frequent hypertension and higher serum creatinine levels than non/ex-smokers at the time of diagnosis, which was apparent with increased smoking dose. The percentages of global glomerulosclerosis and arteriolar hyalinosis increased with increased smoking dose, whereas tubulointerstitial fibrosis or arterial intimal thickening did not. Glomerular mesangial alpha-smooth muscle actin expression were similar between current and non/ex-smokers matched for age, gender, hypertension, and histologic severity, although the number of glomerular CD68+ cells was significantly fewer in smokers. Initial serum creatinine level, estimated glomerular filtration rate (eGFR), and global glomerulosclerosis were found to be risk factors of serum creatinine doubling in both smokers and non/ex-smokers by univariate analysis during a mean follow-up of 3.8 years. CONCLUSION: In addition to dose dependent renal functional decline and hypertension, smoking contributes to renal disease progression by eliciting microvascular injury in IgAN patients.

Prevalencia de glomerulopatías en el paciente mayor de 65 años: correlación clínica e histológica en centro de referencia nacional, período 2009-2013 / Glomerulopathies prevalence in patients older than 65 years: clinical and histological correlation in national reference center, 2009-2013

Determinar las características clínicas y demográficas, la frecuencia y la presentación clínica de las glomerulopatías en el paciente mayor de 65 años. Material y métodos. Estudio de tipo transversal-descriptivo, que incluye la revisión de los datos clínicos e informes anatomopatológicos de 1 338 pacientes biopsiados en hospitales de Lima y otras principales regiones de Perú, se seleccionaron 47 pacientes mayores de 65 años en el del período enero de 2009 a diciembre de 2013. Resultados. La distribución por sexos fue femenino 18 (38 %) y masculino 29 (62 %). Las principales características de la población fueron hipertensión (23 %), edema (74 %), síndrome nefrótico (49 %), hematuria (48 %) y falla renal (21%). La proteinuria promedio fue de 4,2 g/L en 24 h por 1,73 m2 SC +/- 3,2 y la creatinina, 1,7 mg/dL +/- 0,8. Las glomerulopatías (primarias representaron 90 % de los resultados. Los diagnósticos histopatológicos fueron glomerulonefritis (GN) primarias: glomeruloesclerosis focal y segmentaria (GEFS) 13 (52%), glomerulonefritis membranosa (GNM) 7 (15%) y amiloidosis 4 (9%). GN secundarias: nefritis lúpica y las GN membranoproliferativas (GNMP) 4%, la GEN diabética y las vasculitis fueron hallazgos poco frecuentes. Conclusiones. La glomeruloesclerosis focal y segmentaria fue la más frecuente en mayores de 65 años, más común en varones que en mujeres y las presentaciones clínicas predominantes fueron el edema y el síndrome nefrótico...

To determine the clinical and demographic features, frequency and clinical presentation of glomerulopathies in patients older than 65 years. Material and methods. We performed a cross-descriptive study, including review of clinical data and pathology reports of 1338 patients undergoing percutaneous renal biopsy in hospital centers of Lima and the main interior regions of Peru, selected a total of 47 patients over 65 years within the period of January 2009 to December 2013. Results. The gender distribution was: Female 18 cases (38 %) and male 29 cases (62%). Hypertension 23 %, edema 74 %, nephrotic syndrome 49 %, hematuria 48 % and renal failure 21 % were the principal features of the population. The average proteinuria was 4,2 g/L at 24 hours per 1,73 m2 SC +/- 3,2 and creatinine was 1,7 mg/dL +/- 0,8. The primary glomerulopathies accounted for 90 % of the results. The histopathological diagnoses were: GN primary: focal segmental glomerulosclerosis (FSGS) with 13 cases (52 %), membranous glomerulonephritis (MGN) with 7 cases (15 %) and amyloidosis with 4 cases (9 %). GN Secondary: lupus nephritis and membranous proliferative GN (MPGN), the diabetic GEN vasculitis and rare findings. The mean clinical presentation was nephrotic syndrome (49 %) followed by renal failure (21 %). Conclusions. FSGS is the most frequent glomerulopathy in people over 65 years, more common in males and the predominant clinical presentation was edema and nephrotic syndrome...

Co-existence of thin basement membrane nephropathy with other glomerular pathologies; a single center experience

The co-existence of thin basement membrane nephropathy [TBMN] and another glomerular pathology portends a worse prognosis than TBMN alone. The purpose of our study was to investigate the prevalence of TBMN and associated glomerular pathologies at our institution. We reviewed all renal biopsies performed at Saint Louis University hospital over a 7-year period. We excluded all post transplant biopsies, and biopsies showing diabetic glomerulopathy, membranoproliferative glomerulopathy, membranous glomerulopathy, and biopsies where no electron microscopy or immunofluorescent studies were done. All other biopsies were included. A total of 634 biopsies were included in the study. The prevalence of TBMN was 47 [7.4%], of whom 17 [36.2%] had TBMN alone. In the remaining 30 [63.8%] patients TBMN was associated with other glomerular pathologies: IgAN 9 [19.1%] and FSGS 9 [19.1%]. We found significantly higher prevalence of IgAN in patients with TBMN versus all biopsies [19.1% vs. 7.7%, respectively, P = 0.002]. We found significant similarities in biopsy indications for TBMN and IgAN group. Around two thirds of the cases of TBMN were associated with other glomerular pathologies. The prevalence of IgAN, but not focal segmental glomerulosclerosis, was significantly higher in patients with TBMN as compared to the general renal biopsy specimens

Rifampicin-Induced Minimal Change Disease Is Improved after Cessation of Rifampicin without Steroid Therapy

There are several reports to demonstrate that rifampicin, a major anti-tuberculosis agent, is associated with some adverse renal effects, with a few cases of rifampicin-induced minimal change disease (MCD). In the present case, a 68-year-old female presented with nausea, vomiting, foamy urine, general weakness and edema. She had been taking rifampicin for 4 weeks due to pleural tuberculosis. The patient had no proteinuria before the anti-tuberculosis agents were started, but urine tests upon admission showed heavy proteinuria with a 24-h urinary protein of 9.2 g/day, and serum creatinine, albumin, and total cholesterol levels were 1.36 mg/dL, 2.40 g/dL, and 283 mg/dL, respectively. MCD was diagnosed, and the patient achieved complete remission after cessation of rifampicin without undergoing steroid therapy.

Patofisiología de la hiperfiltración glomerular en la diabetes. Parte II / Pathophysiology of glomerular hyperfiltration in diabetes. Part II

La hiperfiltración glomerular (HF) en la enfermedad renal diabética es un complejo fenómeno hemodinámico que ocurre en etapas tempranas de la evolución de la enfermedad, y muy probablemente tenga influencias negativas, en cuanto a la progresión hacia la aparición de la microalbuminuria y la evolución de la nefropatía diabética (NFDBT) evidente. Los factores involucrados en su fisiopatología son múltiples, e incluyen al medio diabético y numerosos factores humorales como óxido nítrico, prostaglandinas, sistema renina angiotensina aldosterona, péptido auricular natriurético, especies reactivas de oxígeno y otros factores humorales y de crecimiento, que actúan básicamente provocando o potenciando la vasodilatación de la arteriola aferente (AA)...

Glomerular hyperfiltration (GH) in diabetic renal disease is a complex hemodynamic phenomenon that occurs early in the course of the disease and most likely has associated with poor prognosis with respect to the development of microalbuminuria and overt diabetic nephropathy. The factors involved in its pathophysiology are multiple and include the diabetic milieu and the effects of several humoral factors such as nitric oxide, prostaglandins, renin angiotensin aldosterone system, atrial natriuretic peptide, reactive oxygen species and other humoral and growth factors that act basically causing or enhancing the afferent arteriole vasodilation (AA)...

Impacto de la glomerulopatía post trasplante en la sobrevida del injerto renal / Post-transplant glomerulopathy impact in renal graft survival

Introducción: las glomerulopatías primarias son causa de enfermedad renal crónica en receptores de trasplante renal (30%-50%), siendo un determinante importante en la sobrevida del injerto. Recientes estudios revelan que la recurrencia fue la tercer causa más frecuente de pérdida delinjerto a 10 años de seguimiento postrasplante. Objetivo: Analizar el impacto de las glomerulopatía postrasplante como predictor de pérdida del injerto. Material y métodos: Entre enero de 1990 y abril del 2013 se realizaron 849 biopsias renales en 375 pacientes trasplantados, diagnosticándose 50 casos de glomerulopatía. Se comparó dicha población con un grupo histórico de receptores de trasplante renal entre 2000 al 2011, sin glomerulopatía. Se analizó la sobrevida del injerto renal en ambas poblaciones. Resultados: Se diagnosticaron 50 glomerulopatías post trasplante en 47 pacientes. No encontramos diferencias estadísticamente significativas entre este grupo y el grupo histórico en: edad del receptor; sexo del donante; tipo del donante; n¿²mero de miss match; tiempo de isquemia del órgano; tasa de rechazo agudo; retardo de la función del injerto; ni en la mortalidad del receptor. Si hallamos diferencias significativa en sexo masculino, 88 vs 55% (p< 0.05). La tasa de pérdida del injerto renal fue significativamente más frecuente entre los pacientes que presentaron enfermedad glomerular 38 vs 8% (p< 0.01). Conclusión: En nuestra población, la aparición de glomerulopatía post trasplante se asoció a una disminución de la sobrevida del injerto observándose una mayor tasa de pérdida en la glomerulopatía membranoproliferativa.

Introduction: primary glomerulopathy is cause of renal chronic disease in renal transplant recipients (30%-50%), being an important determinant in graft survival. Recent studies reveal that recurrence was the third most frequent cause of graft lost after 10 years post-transplant monitoring process. Objective: To analyze posttransplant glomerulopathy impact as a graft lost predictor. Methods: Between January 1990 and April 2013, 849 renal biopsies were carried out on 375 transplanted patients, 50 glomerulopathy cases were diagnosed. This population was compared with an historical renal transplant recipients group between 2000 to 2011, without glomerulopathy. Renal graft survival was analyzed in both populations. Results: 50 post-transplant glomerulopathies were diagnosed in 47 patients. We did not find statistically significant differences between this group and the historical one concerning recipient age, donor sex, donor type, miss match number, organ ischaemia time, acute rejection rate, delayed graft function, and neither in the recipient mortality. We did find significant differences in male sex, 88% vs 55% (p< 0.05). Renal graft lost rate was significantly more frequent among patients presenting glomerular disease 38 vs 8 % (p< 0.01). Conclusion: In our population, post transplant glomerulopathy was associated to graft survival reduction and a higher membranoproliferative glomerulopathy lost rate was observed.

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.

Glomerulonefritis fibrilar: Una rara forma de enfermedad glomerular por depósitos organizados / Fibrillary glomerulo-nephritis: A rare form of glomerular disease with organized deposits

Se describe el caso de una mujer de 67 años de edad que consultó por debilidad y astenia, constatándose proteinuria de rango nefrótico y dislipemia. Se realizó punción para biopsia renal, la que se analizó por microscopia óptica, inmunofluorescencia y microscopia electrónica de transmisión. El análisis ultra-estructural reveló la existencia de depósitos fibrilares organizados, rectos, no ramificados, cuyo espesor osciló entre 15 y 20 nm. Dichas fibrillas ópticamente se veían como una expansión mesangial discretamente nodular, ligeramente PAS positiva, rojo Congo negativa y débilmente positiva para IgG. El diagnóstico fue glomerulonefritis fibrilar. Las enfermedades glomerulares por depósitos organizados pueden exhibir superposición sindrómica e histopatológica. Por tal motivo, resulta de importancia una primera separación entre aquellas rojo Congo positivas o negativas, siendo en este último caso la microscopia electrónica de transmisión la que diferencia dos entidades: la glomerulonefritis fibrilar y la glomerulonefritis inmunotactoide. Esta diferencia se apoya no sólo en las características ultraestructurales, sino en sus características clínicas. La glomerulonefritis inmunotactoide muestra una fuerte asociación con procesos linfoproliferativos, a diferencia de lo que ocurre con la glomerulonefritis fibrilar.

We describe the case of a 67 year-old female who presented weakness and fatigue. Laboratory data showed nephrotic level of proteinuria and dyslipidemia. A renal biopsy was performed, and studied by light microscopy, immuno-fluorescence and electron microscopy. Ultra-structural analysis revealed the existence of organized fibrillary deposits, straight and without ramifications, the thickness of which ranged from 15 to 20 nm. These fibres were identified, by light microscopy, as slightly nodular mesangial expansions PAS positive, Congo red negative and weakly positive for IgG. Given the above findings, the diagnosis was fibrillary glomerulonephritis. Glomerular lesions with organized deposits may exhibit syndromic and pathological overlap. For this reason it is important to initially discriminate between positive and negative Congo red deposits, using, in the latter case, transmission electron microscopy to distinguish between immuno-tactoid and fibrillary glomerulonephritis. This differentiation relies not only on ultrastructural features, but on different clinical characteristics. Unlike what happens with fibrillary glomerulonephritis, the immuno-tactoid shows a strong association with lymphoproliferative processes.

Frequency of primary glomerular disease in northeastern China

Most frequently reported Chinese renal biopsy data have originated from southeastern China. The present study analyzed the renal biopsy data from northeastern China. The records of 1550 consecutive native patients who were diagnosed with primary glomerular diseases (PGD) after renal biopsy at our hospital during 2005-2009 were used. These patients were divided into four age groups for stratified analysis: <15, 15-44, 45-59, and ≥60 years old. Among PGD, minimal change disease (MCD) was the most common histologically diagnosed disease (30.7 percent), followed by IgA nephropathy (IgAN), mesangial proliferative glomerulonephritis (MsPGN), membranous nephropathy (MN), membranoproliferative glomerulonephritis (MPGN), focal segmental glomerulosclerosis (FSGS), and endocapillary proliferative glomerulonephritis (EnPGN). MCD was the disease most frequently observed (43.7 percent) in the <15-year-old group. MsPGN was the most common disease in the elderly group (38.1 percent). MsPGN was more prevalent in females (27.8 percent), whereas MCD was more prevalent in males (35.3 percent). Primary glomerular diseases constituted the most commonly encountered group of diseases with a high prevalence of MCD, which predominantly affected males and young adults. The prevalence of MCD was high in northeastern China. Further study is necessary to expand the epidemiologic data available for renal disease in China.

Morphologic evaluation of renal function using semi-quantitative method in primary nonproliferative glomerular diseases.

Context: Fibrosis is universally accepted as a poor prognostic finding in renal pathology. Semi-quantitative assessment is widely used for prognostication in pathology. Aims: We propose a semi-quantitative method to prognosticate primary nonproliferative glomerular diseases. Settings and Design: A semi-quantitative method based on Banff schema, 97 classification has been modified to suit the requirements. Glomerular, tubulointerstitial, and vascular compartments were scored independently, and the scores were totaled to obtain total scores. Materials and Methods: Seventy-six renal biopsies were assessed by semi-quantitative scores and the individual compartmental and total scores were correlated with serum creatinine levels. Follow-up was available in 24 cases. Statistical Analysis: Pearson correlation coefficient, two-tailed t test, to determine the P value. Results: P values were significant for the total scores as well as individual compartments. There is a linear correlation between the scores and serum creatinine levels. A total score of ≥5 was significant. Conclusions: The semi-quantitative scoring system based on modified Banff schema, 1997 is useful in prognosticating renal biopsies in primary nonproliferative glomerular diseases.

Histologic alterations of rat kidneys perfused with a Euro-Collins diltiazem solution / Alterações histológicas ocorridas em rins de ratos perfundidos com solução de Euro-Collins associada à diltiazem

PURPOSE: Analyse the histologic changes of rat kidneys perfused with isotonic saline solution (ISS), Euro-Collins solution (ECS) and Euro-Collins solution with diltiazem (ECSD). METHODS: Thirty-six Wistar rats were used divided equally, as follow: group A (ISS), group B (ECS) and group C (ECSD). Through a catheter placed into the abdominal aorta, a renal perfusion was performed using a solution according to the group to which the animal belonged. After the complete perfusion, bilateral nephrectomy was performed and the organs were preserved under hypothermia for five distinct periods of time. Glomerulus and tubule were evaluated through optical microscopy. RESULTS: Renal perfusion with ECS and ECSD proved effectiveness in the preservation of the organs up to 36 hours and an increase in the percentage of injured glomeruli was noticed only in the period of 48 hours. CONCLUSIONS: The results showed that exists an association between the tubular injury and the glomeruli lesion degree; kidneys with a higher degree of tubular damage were related to severe glomerular lesion. Also, the addition of a calcium channel blocker, diltiazem, to the ECS for the renal perfusion does not decrease the percentage of glomerular lesion.

OBJETIVO: Analisar as alterações histológicas nos rins de ratos perfundidos com solução salina isotônica (ISS), solução Euro-Collins (ECS) e solução Euro-Collins com diltiazem (ECSD). MÉTODOS: Foram divididos, de forma igual, 36 ratos Wistar, como se segue: grupo A (ISS), grupo B (ECS), grupo C (ECSD). Através de um cateter localizado na aorta abdominal, foi realizada a perfusão renal com a solução de acordo com o grupo ao qual o animal pertencia. Após a perfusão total, realizou-se nefrectomia bilateral com a preservação dos órgãos sob hipotermia por cinco períodos distintos de tempo. Glomérulos e túbulos foram avaliados por microscopia óptica. RESULTADOS: Tanto a perfusão renal com ECS quanto a com ECSD provaram sua efetividade na preservação dos órgãos em até 36 horas e aumento da porcentagem de glomérulos injuriados foi notada apenas no período de 48 horas. CONCLUSÕES: Os resultados mostraram haver uma correlação entre a injúria tubular e o grau de lesão glomerular; rins com um maior grau de dano tubular foram relacionados com lesão glomerular severa. Além disso, a adição de um bloqueador de canal de cálcio, diltiazem, à ECS para a perfusão renal não diminui a porcentagem de lesão glomerular.

Achados histopatológicos renais em idosos / Histopathological findings in elderly patients

INTRODUÇÃO: A população idosa mundial tem aumentado de forma expressiva e pesquisas apontam para um aumento da expectativa de vida dos brasileiros em cerca de 10 anos. Assim como outras comorbidades, as doenças glomerulares também são observadas em idosos e, neste contexto, a biopsia renal surge como ferramenta diagnóstica fundamental para auxiliar a tomada de conduta, evitando, muitas vezes, terapias desnecessárias. OBJETIVO: Estabelecer a frequência dos diagnósticos histológicos em idosos submetidos a biopsia renal, com destaque para as glomerulopatias (GPs), em dois centros universitários brasileiros. MÉTODOS: Avaliação retrospectiva dos laudos de biopsias renais do Departamento de Patologia da UNIFESP, incluindo pacientes com idade maior ou igual a 60 anos, no período de 01/01/1996 a 31/12/2003 e do ambulatório de GPs do NIEPEN. Os estudos de rins transplantados e de nefrectomias foram excluídos. Os dados considerados para análise foram: idade, sexo, síndrome clínica de apresentação e diagnóstico histológico (por microscopia óptica e imunofluorescência). As nefropatias foram classificadas em GP primárias, doenças renais secundárias, patologias não glomerulares e outras. RESULTADOS: Foram avaliados 113 casos, constatando-se: média de idade de 66,0 ± 6,0 anos e predomínio do sexo masculino (54,8 por cento). A síndrome clínica de apresentação mais comum foi a síndrome nefrótica (32,7 por cento), seguida de insuficiência renal aguda e crônica, com 18,6 por cento cada. As doenças glomerulares foram: nefropatia membranosa (NM), 15 por cento; nefroesclerose hipertensiva, 11,5 por cento; glomerulosclerose segmentar e focal e vasculites/ GN com crescentes, 9,7 por cento cada; amiloidose, glomerulonefrite crônica e doença de lesões mínimas, 7,1 por cento cada; GN proliferativa difusa, 4,4 por cento; nefropatia por IgA e nefrite lúpica, 2,7 por cento cada. Houve um predomínio das GP primárias (45,2 por cento) quando comparadas às outras nefropatias. CONCLUSÃO: A principal indicação de biopsia foi a síndrome nefrótica. Predominaram as doenças glomerulares entre os diagnósticos histológicos renais, com destaque para NM e nefroesclerose hipertensiva, achados compatíveis com estudos prévios nesta área, mas raramente avaliados em nosso meio. Fica claro que a diversidade de diagnósticos e os tratamentos diferenciados justificam a biopsia renal para tomada de decisão neste grupo de pacientes.

INTRODUCTION: The elderly population has significantly increased worldwide and recent studies have evidenced a 10-year increase in Brazilian life expectancy. Similarly to other comorbidities, glomerular diseases are also observed in the elderly, and, in that age group, kidney biopsy emerges as a fundamental diagnostic tool to help disease management, preventing unnecessary therapies. OBJECTIVE: To establish the frequency of histological diagnoses in the elderly undergoing kidney biopsy, with an emphasis on glomerulopathies (GPs), at two Brazilian universities. METHODS: Retrospective assessment of kidney biopsy reports of the Department of Pathology of UNIFESP (patients aged 60 years or above, from 01/01/1996 to 12/31/2003) and of the outpatient clinic of GPs of NIEPEN. The studies of transplanted kidneys and nephrectomies were excluded. The following data were analyzed: age; sex; clinical syndrome at presentation; and histological diagnosis (light microscopy and immunofluorescence). Nephropathies were classified as primary GPs, secondary kidney diseases, nonglomerular diseases, and others. RESULTS: One hundred and thirteen biopsies were assessed, the mean age of patients was 66.0 ± 6.0 years, and the male sex prevailed (54.8 percent). The most common clinical presentation was nephrotic syndrome (32.7 percent), followed by acute and chronic kidney failure (18.6 percent, each). Glomerular diseases were as follows: membranous nephropathy (MN), 15 percent; hypertensive nephrosclerosis, 11.5 percent; focal segmental glomerulosclerosis and vasculitis/crescentic GN, 9.7 percent each; amyloidosis, chronic glomerulonephritis, and minimal change disease, 7.1 percent each; diffuse proliferative GN, 4.4 percent; IgA nephropathy and lupus nephritis, 2.7 percent each. Primary GPs predominated (45.2 percent) as compared with other nephropathies. CONCLUSION: Nephrotic syndrome was the major indication for kidney biopsy. Regarding the kidney histological diagnoses, glomerular diseases predominated, in particular MN and hypertensive nephrosclerosis, findings compatible with previous studies in the area, but rarely assessed among us. It is clear that the diversity of diagnoses and differentiated treatments justify kidney biopsy for decision making in that group of patients.

Glomerular damage as a predictor of renal allograft loss

Interstitial fibrosis and tubular atrophy (IF/TA) are the most common cause of renal graft failure. Chronic transplant glomerulopathy (CTG) is present in approximately 1.5-3.0 percent of all renal grafts. We retrospectively studied the contribution of CTG and recurrent post-transplant glomerulopathies (RGN) to graft loss. We analyzed 123 patients with chronic renal allograft dysfunction and divided them into three groups: CTG (N = 37), RGN (N = 21), and IF/TA (N = 65). Demographic data were analyzed and the variables related to graft function identified by statistical methods. CTG had a significantly lower allograft survival than IF/TA. In a multivariate analysis, protective factors for allograft outcomes were: use of angiotensin-converting enzyme inhibitor (ACEI; hazard ratio (HR) = 0.12, P = 0.001), mycophenolate mofetil (MMF; HR = 0.17, P = 0.026), hepatitis C virus (HR = 7.29, P = 0.003), delayed graft function (HR = 5.32, P = 0.016), serum creatinine ≥1.5 mg/dL at the 1st year post-transplant (HR = 0.20, P = 0.011), and proteinuria ≥0.5 g/24 h at the 1st year post-transplant (HR = 0.14, P = 0.004). The presence of glomerular damage is a risk factor for allograft loss (HR = 4.55, P = 0.015). The presence of some degree of chronic glomerular damage in addition to the diagnosis of IF/TA was the most important risk factor associated with allograft loss since it could indicate chronic active antibody-mediated rejection. ACEI and MMF were associated with better outcomes, indicating that they might improve graft survival.