Glomerulopatía colapsante en un paciente con Covid-19. Reporte de caso / Collapsing glomerulonephritis in a COVID-19 patient. Case report

La injuria renal aguda por glomerulopatía colapsante, presenta alta morbimortalidad, incluso con requerimiento de diálisis crónica; la Covid-19 es una de sus causas. Se presenta el caso de un paciente con Covid-19 y glomerulopatía colapsante. Varón de 17 años, sin antecedentes patológicos; con historia de cuatro meses de edema, orina espumosa y disminución del flujo urinario. Al examen: anasarca. Exámenes: creatinina 4,2 mg/dl, albumina 1,9 gr/dl, colesterol y triglicéridos aumentados; orina: proteinuria 6,7 gr/24h, leucocituria y hematuria con urocultivo negativo. Serología para VIH, sífilis y hepatitis negativos. Inmunología para lupus negativa, prueba rápida para la Covid-19 IgG (+). La biopsia renal mostró Glomeruloesclerosis Focal y Segmentaria, variante Colapsante. Recibió corticoides y ciclosporina. La creatinina mejoró, la proteinuria se mantiene >3 gr/24horas.

SUMMARY Acute renal injury due to collapsing glomerulonephritis is associated with high morbidity and mortality, requiring chronic dialysis, COVID-19 is one of its causes. A 17-year-old male patient presented with a four-month history of edema, foamy urine and reduction in the urine flow; anasarca was observed at physical examination. Laboratory values showed creatinine 4,2 mg/dl; albumin 1,9 gr/dl; cholesterol and triglycerides were high; proteinuria 6,7 gr/24h: leucocyturia and hematuria with negative urine culture. Serologies for HIV, syphilis and hepatitis were negative. Studies for systemic lupus were negative. An antigenic test for SARS-CoV-2 was positive as well as an IgG. Renal Biopsy showed Focal and Segmental Glomerulosclerosis, Collapsing variant. He received corticosteroids and cyclosporine. Creatinine improved; proteinuria remained >3 gr/24 hours.

Long-term prognostic analysis of IgA nephropathy with focal segmental glomerulosclerosis in children / 中华肾脏病杂志

Objective:To analyze the long-term prognosis of IgA nephropathy (IgAN) with focal segmental glomerulosclerosis (FSGS) and the risk factors related to renal prognosis in children with IgAN-FSGS.Methods:A retrospective study was concluded in IgAN-FSGS children who were followed up for more than 5 years and diagnosed by renal biopsy for the first time in the Eastern Theater General Hospital from January, 2004 to December, 2018. The end-point events of the study were entering end-stage kidney disease (ESKD) or estimated glomerular filtration rate (eGFR) decreased by ≥50% from baseline, which were defined as poor renal prognosis. Baseline clinicopathologic data of IgAN-FSGS children were compared between the end-point event group and the non-end-point event group. The cumulative renal survival rate of IgAN-FSGS children was calculated by Kaplan-Meier survival analysis. The influencing factors of poor renal prognosis in IgAN-FSGS children were analyzed by Cox proportional hazards model, and the diagnostic value was evaluated by the receiver operating characteristic curve (ROC curve) and area under the curve (AUC). The diagnostic value was verified by time dependent-ROC and time dependent-AUC.Results:A total of 204 IgAN-FSGS children were enrolled in this study, of whom 132 cases were males (64.7%). The median age of renal biopsy was 16 (14, 17) years old. During a median follow-up time of 90.7 (71.7, 114.8) months, 57 cases (27.9%) reached the end-point events. Compared with the non-end-point event group ( n=147), the end-point event group ( n=57) had higher proportions of males and hypertension, higher levels of 24-hour urinary protein, serum creatinine, serum uric acid, urinary N-acetyl-β- D-glucosaminidase, urinary retinol binding protein, higher proportions of glomerular segmental sclerosis (S1) ≥25% and tubular atrophy/interstitial fibrosis (T1/T2), and lower levels of serum albumin, serum IgA, and serum IgG (all P<0.05). There was no statistical difference between the two groups in treatment (all P>0.05). Kaplan-Meier survival analysis showed that with entry of ESKD or eGFR decreased by ≥50% from baseline as the end-point events, the 5-year, 10-year, and 15-year cumulative renal survival rates in IgAN-FSGS children were 88.7%, 67.6%, and 50.7%, respectively. Multivariate Cox regression analysis showed that proteinuria >1 g/24 h ( HR=3.702, 95% CI 1.657-8.272, P=0.001), hyperuricemia ( HR=3.066, 95% CI 1.793-5.245, P<0.001), S1≥25% ( HR=2.017, 95% CI 1.050-3.874, P=0.035), T1/T2 ( HR=1.863, 95% CI 1.021-3.158, P=0.016) were the independent related factors for poor renal prognosis. ROC curve analysis showed that S1≥25% ( AUC=0.605, P=0.021, sensitivity 26.3%, specificity 94.6%), T1/T2 ( AUC=0.624, P=0.006, sensitivity 43.9%, specificity 81.0%), hyperuricemia ( AUC=0.658, P<0.001, sensitivity 52.6%, specificity 78.9%), proteinuria>1 g/24 h ( AUC=0.670, P<0.001, sensitivity 87.7%, specificity 46.3%) could accurately predict the renal outcome of IgAN-FSGS. Time dependent-ROC curve validation showed that the combined diagnosis of S1≥25%, T1/T2, hyperuricemia and proteinuria>1 g/24 h had a good predictive value for renal prognosis (3-year AUC=0.846 and 5-year AUC=0.777, respectively). Conclusions:During a median follow-up of 90.7 months, 27.9% of IgAN-FSGS children have poor renal prognosis, and the 5-year, 10-year, and 15-year cumulative renal survival rates are 88.7%, 67.6%, and 50.7%, respectively. Urinary protein >1 g/24 h, hyperuricemia, T1/T2, and S1 ≥25% are the risk factors for renal prognosis in IgAN-FSGS children.

Clinical and pathological features in children diagnosed with primary focal segmental glomerulosclerosis after repeated renal biopsy / 中华肾脏病杂志

Objective:To analyze the clinical and pathological characteristics in children diagnosed with primary focal segmental glomerulosclerosis (FSGS) after repeated renal biopsy.Methods:The clinicopathological data of children who ever experienced renal biopsy in Jinling Hospital from January 1, 2000 to December 31, 2020 were retrospectively reviewed. Clinical manifestations, pathological characteristics and treatment responses were analyzed.Results:Of the 34 enrolled patients, there were 22 males and 12 females. The median age of the first renal biopsy was 14 years old (1-18 years old), and the median interval between repeat renal biopsy and first renal biopsy was 6 months (1-151 months). Thirty-one showed nephrotic syndrome, of which 22 had microscopic hematuria, and 4 had elevated serum creatinine. Among the other 3 patients, 2 had hematuria and proteinuria, and 1 had proteinuria. In the first renal biopsy, 16 cases were diagnosed as minimal change disease, 14 cases were diagnosed as mesangial proliferative glomerulonephritis, 2 cases were diagnosed as IgA nephropathy, and 2 cases were diagnosed as IgM nephropathy. All 34 children showed poor responses to hormone and immunosuppressive therapies. The pathological features of the first renal biopsy in some patients were adhesion (2/34), decreased loop podocyte attachment (2/34), peripheral loop extension to the urinary pole (2/34), renal tubular reflux (4/34), capillary thrombosis (2/34) and IgM deposition (12/34).Conclusions:The initial diagnosis of FSGS is difficult, and the lesions are atypical and easily misdiagnosed. The patients have poor responses to hormone and immunosuppressive therapies. For patients with the pathological changes of adhesion, decreased loop podocyte attachment, peripheral loop extension to the urinary pole, renal tubular reflux, capillary thrombosis and IgM deposition, follow-up is required, and if necessary, repeat renal biopsy needs be performed to determine whether it is FSGS.

Nefropatía por inmunoglobulina M: características histopatológicas y clínicas. Serie de casos / Immunoglobulin M nephropathy: histopathological and clinical characteristics. Case series

La nefropatía por inmunoglobulina M (NIgM) es una glomerulopatía idiopática caracterizada por depósitos mesangiales globales y difusos de IgM. Se realizó un estudio retrospectivo de las características clínicas e histopatológicas de los pacientes con NIgM atendidos en nuestro servicio. De 241 biopsias renales, 21 correspondieron a NIgM (8,7 %). Se incluyeron 18 pacientes (14 de sexo femenino, mediana de edad: 3,08 años). Se excluyó a 1 paciente por enfermedad sistémica asociada y a 2 por seguimiento menor a 1 año. Catorce pacientes se manifestaron con síndrome nefrótico (SN) y 4 con proteinuria aislada o asociada a hematuria. En la microscopia óptica, 13 presentaron hiperplasia mesangial, y 5 esclerosis focal y segmentaria. De los pacientes con SN, 7 fueron corticorresistentes, 4 corticodependientes y 3 presentaban recaídas frecuentes. Todos los pacientes con SN y 1 con proteinuria-hematuria recibieron inmunosupresores; los 18 pacientes recibieron, además, antiproteinúricos. Luego de 5,2 años (2-17,5) de seguimiento, 6 pacientes evolucionaron a enfermedad renal crónica

Immunoglobulin M nephropathy (IgMN) is an idiopathic glomerulopathy characterized by diffuse global mesangial deposits of IgM. We retrospectively studied the clinical and histopathological characteristics of the patients with IgMN seen in our service. Of 241 renal biopsies, 21 corresponded to IgMN (8.7 %). One patient was excluded due to associated systemic disease and 2 due to follow-up less than 1 year, 18 were included (14 girls, median age 3.08 years). Fourteen manifested with nephrotic syndrome (NS) and the remaining with proteinuria (isolated or associated with hematuria). On light microscopy, 13 had hyperplasia with mesangial expansion and 5 had focal and segmental sclerosis. Of the patients with NS, 7 were steroid-resistant, 4 steroid-dependent, and 3 frequent relapsers. All patients with NS and 1 with proteinuria-hematuria received immunosuppressants; the 18 patients also received antiproteinuric drugs. After 5.2 years (2-17.5) of follow-up, 6 patients developed chronic kidney disease.

Collapsing focal segmental glomerulosclerosis probably triggered by dengue virus infection - two case reports / Glomeruloesclerose Segmentar e Focal Colapsante provavelmente desencadeada por infecção pelo vírus da dengue - dois relatos de caso

Abstract The reported cases describe the association between collapsing focal segmental glomerulosclerosis (FSGS) and acute dengue virus infection. In both cases, patients were diagnosed with dengue virus infection and had a severe kidney disease, with nephrotic syndrome and acute kidney injury. Kidney biopsy was performed and showed collapsing FSGS. The first patient, a 27-year-old man, was diagnosed with dengue virus infection and developed nephrotic syndrome after two weeks of illness. He was treated with methylprednisolone for three days and intravenous furosemide. This patient evolved well, although his renal function did not fully recover. The second patient, a 32-year-old man, was diagnosed with a milder clinical presentation of dengue virus infection. He had a past medical history of nephrotic syndrome in childhood, which might have caused its relapse. This patient was treated with intravenous furosemide and also did not fully recover renal function. These cases highlight the possible implication of dengue virus infection in the etiology of collapsing variant of FSGS. Healthcare professionals should be prepared to identify similar cases.

Resumo Os casos relatados descrevem a associação entre glomeruloesclerose segmentar e focal (GESF) colapsante e infecção aguda pelo vírus da dengue. Nas duas instâncias os pacientes foram diagnosticados com infecção pelo vírus da dengue e apresentaram doença renal grave, com síndrome nefrótica e insuficiência renal aguda. A biópsia renal revelou a presença de GESF colapsante. O primeiro paciente, um homem de 27 anos, foi diagnosticado com infecção pelo vírus da dengue e desenvolveu síndrome nefrótica após duas semanas de doença. Ele foi tratado com metilprednisolona por três dias e furosemida endovenosa. O paciente evoluiu bem, embora sua função renal não tenha se recuperado plenamente. O segundo paciente, um homem de 32 anos, foi diagnosticado com apresentação clínica mais discreta de infecção pelo vírus da dengue. Ele tinha histórico de síndrome nefrótica na infância, o que pode ter causado a recidiva. O paciente foi tratado com furosemida endovenosa e também não recuperou plenamente sua função renal. Os dois casos destacam a possível implicação da infecção pelo vírus da dengue na etiologia da variante colapsante da GESF. Os profissionais de saúde devem estar preparados para identificar casos semelhantes.

Rare inherited kidney diseases: an evolving field in Nephrology / Doenças renais hereditárias raras: um campo em evolução na Nefrologia

Abstract There are more than 150 different rare genetic kidney diseases. They can be classified according to diagnostic findings as (i) disorders of growth and structure, (ii) glomerular diseases, (iii) tubular, and (iv) metabolic diseases. In recent years, there has been a shift of paradigm in this field. Molecular testing has become more accessible, our understanding of the underlying pathophysiologic mechanisms of these diseases has evolved, and new therapeutic strategies have become more available. Therefore, the role of nephrologists has progressively shifted from a mere spectator to an active player, part of a multidisciplinary team in the diagnosis and treatment of these disorders. This article provides an overview of the recent advances in rare hereditary kidney disorders by discussing the genetic aspects, clinical manifestations, diagnostic, and therapeutic approaches of some of these disorders, named familial focal and segmental glomerulosclerosis, tuberous sclerosis complex, Fabry nephropathy, and MYH-9 related disorder.

Resumo As doenças renais genéticas raras compreendem mais de 150 desordens. Elas podem ser classificadas segundo achados diagnósticos como (i) distúrbios do crescimento e estrutura, (ii) doenças glomerulares, (iii) tubulares e (iv) metabólicas. Nos últimos anos, houve uma mudança de paradigma nesse campo. Os testes moleculares tornaram-se mais acessíveis, nossa compreensão sobre os mecanismos fisiopatológicos subjacentes a essas doenças evoluiu e novas estratégias terapêuticas foram propostas. Portanto, o papel do nefrologista mudou progressivamente de mero espectador a participante ativo, parte de uma equipe multidisciplinar, no diagnóstico e tratamento desses distúrbios. O presente artigo oferece um panorama geral dos recentes avanços a respeito dos distúrbios renais hereditários raros, discutindo aspectos genéticos, manifestações clínicas e abordagens diagnósticas e terapêuticas de alguns desses distúrbios, mais especificamente a glomeruloesclerose segmentar e focal familiar, complexo da esclerose tuberosa, nefropatia de Fabry e doença relacionada ao MYH9.

Focal and Segmental Glomerulosclerosis and Membranous Nephropathy overlapping in a patient with Nephrotic Syndrome: a case report / Glomeruloesclerose Segmentar e Focal e Nefropatia Membranosa sobrepostas em paciente com Síndrome Nefrótica: relato de caso

Abstract Introduction: Some cases of membranous nephropathy (MGN) present focal segmental glomerulosclerosis (FSGS) typically associated with disease progression. However, we report a case of a patient who seemed to have MGN and FSGS, both primary. Case presentation: A 17-year-old female, Caucasian, presenting lower extremity edema associated with episodes of foamy urine and high blood pressure, had physical and laboratorial exams indicating nephrotic syndrome. A renal biopsy was performed and focal and segmental glomerulosclerosis were observed under light microscopy in some glomeruli presented as tip lesion, and in others it was accompanied by podocyte hypertrophy and podocyte detachment in urinary space, compatible with podocytopathy FSGS. Besides, there were thickened capillary loops with basement membrane irregularities due to "spikes" compatible with MGN stage II. Immunofluorescence showed finely granular IgG, IgG4, and PLA2R deposits in capillary loops and, in electron microscopy, subepithelial deposits and foot process effacement. These morphological findings are compatible with FSGS and MGN stage II. Conclusions: In the present case, clinical and morphological characteristics showed a possible overlap of primary FSGS and MGN as focal and segmental glomerulosclerosis does not seem to be related with MGN progression but with the podocytopathy FSGS.

Resumo Introdução: Alguns casos de nefropatia membranosa (NM) apresentam glomeruloesclerose segmentar e focal (GESF) tipicamente associada a progressão da doença. Contudo, relatamos o caso de uma paciente que parece ter NM e GESF, ambas primárias. Apresentação do caso: Uma jovem branca de 17 anos de idade com edema de membros inferiores associado a episódios de urina espumosa e hipertensão apresentou-se com achados físicos e laboratoriais sugestivos de síndrome nefrótica. Foi realizada biópsia renal. GESF foi observada por microscopia de luz em alguns glomérulos que apresentavam lesões de ponta, enquanto em outros o achado era acompanhado por hipertrofia podocitária e descolamento de podócitos no espaço urinário, compatíveis com podocitopatia GESF. Além disso, as alças capilares estavam espessadas com irregularidades na membrana basal devido a "espículas" compatíveis com NM estágio II. Imunofluorescência revelou depósitos finamente granulares de IgG, IgG4 e PLA2R nas alças capilares. Microscopia eletrônica exibiu depósitos subepiteliais e apagamento de pedicelos. Tais achados morfológicos são compatíveis com GESF e NM estágio II. Conclusões: No presente caso, as características clínicas e morfológicas revelaram uma possível sobreposição de GESF primária e NM, uma vez que a glomeruloesclerose segmentar e focal não parece estar relacionada com a progressão da NM, mas com a podocitopatia GESF.

APOL1 risk variants and kidney disease: what we know so far / Variantes de risco APOL1 e doença renal: o que sabemos até agora

ABSTRACT There are striking differences in chronic kidney disease between Caucasians and African descendants. It was widely accepted that this occurred due to socioeconomic factors, but recent studies show that apolipoprotein L-1 (APOL1) gene variants are strongly associated with focal segmental glomerulosclerosis, HIV-associated nephropathy, hypertensive nephrosclerosis, and lupus nephritis in the African American population. These variants made their way to South America trough intercontinental slave traffic and conferred an evolutionary advantage to the carries by protecting against forms of trypanosomiasis, but at the expense of an increased risk of kidney disease. The effect of the variants does not seem to be related to their serum concentration, but rather to local action on the podocytes. Risk variants are also important in renal transplantation, since grafts from donors with risk variants present worse survival.

RESUMO Existem importantes diferenças na doença renal crônica entre caucasianos e afrodescendentes. Foi amplamente aceito que isso ocorreu devido a fatores socioeconômicos, mas estudos recentes mostraram que as variantes gênicas da apolipoproteína L-1 (APOL1) estão fortemente associadas à glomeruloesclerose segmentar e focal, nefropatia associada ao HIV, nefroesclerose hipertensiva e nefrite lúpica na população afrodescendente. Essas variantes chegaram à América do Sul através do tráfico intercontinental de escravos, e proporcionaram uma vantagem evolutiva aos portadores, protegendo contra formas de tripanossomíase, mas à custa de um maior risco de doença renal. O efeito das variantes não parece estar relacionado à sua concentração sérica, mas sim à sua ação local sobre os podócitos. Variantes de risco também são importantes no transplante renal, já que enxertos de doadores com variantes de risco apresentam pior sobrevida.

Hydralazine-associated adverse events: a report of two cases of hydralazine-induced ANCA vasculitis / Eventos adversos associados à hidralazina: um relatório de dois casos de vasculite associada ao ANCA induzida por hidralazina

Abstract Hydralazine is a direct-acting vasodilator, which has been used in treatment for hypertension (HTN) since the 1950s. While it is well known to cause drug-induced lupus (DIL), recent reports are indicating the emergence of the drug-induced anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (DIV). Herein, we describe two patients (aged 57 and 87 years) who presented with severe acute kidney injury (AKI), proteinuria, and hematuria. Both were receiving hydralazine for the treatment of hypertension. ANCA serology was positive in both patients along with anti-histone antibodies (commonly seen in drug-induced vasculitis). Renal biopsy revealed classic crescentic (pauci-immune) glomerulonephritis in these patients and hydralazine was discontinued. During the hospital course, the 57-year-old patient required dialysis therapy and was treated with steroids and rituximab for the ANCA disease. Renal function improved and the patient was discharged (off dialysis) with a serum creatinine of 3.6 mg/dL (baseline = 0.9 mg/dL). At a follow-up of 2 years, the patient remained off dialysis with advanced chronic kidney disease (CKD) (stage IIIb). The 87-year-old patient had severe AKI with serum creatinine at 10.41 mg/dL (baseline = 2.27 mg/dL). The patient required hemodialysis and was treated with steroids, rituximab, and plasmapheresis. Unfortunately, the patient developed catheter-induced bacteremia and subsequently died of sepsis. Hydralazine can cause severe AKI resulting in CKD or death. Given this extremely unfavorable adverse-event profile and the widespread availability of alternative anti-hypertensive agents, the use of hydralazine should be carefully considered.

Resumo A hidralazina é um vasodilatador de ação direta, que vem sendo utilizado no tratamento da hipertensão arterial (HA) desde a década de 1950. Embora seja bem conhecido por causar lúpus induzido por drogas (LID), relatórios recentes estão indicando o surgimento da vasculite associada ao anticorpo citoplasmático anti-neutrófilo (ANCA), induzida por drogas (VID). Aqui, descrevemos dois pacientes (com idade entre 57 e 87 anos) que apresentaram lesão renal aguda grave (LRA), proteinúria e hematúria. Ambos estavam usando hidralazina para o tratamento da hipertensão. A sorologia para ANCA foi positiva em ambos os pacientes, juntamente com anticorpos anti-histona (comumente vistos na vasculite induzida por drogas). A biópsia renal revelou glomerulonefrite rapidamente progressiva clássica (pauci-imune) nestes pacientes e a hidralazina foi interrompida. Durante a internação hospitalar, o paciente de 57 anos necessitou de diálise e foi tratado com esteroides e rituximab para a doença do ANCA. A função renal melhorou e o paciente recebeu alta (fora da diálise) com creatinina sérica de 3,6 mg/dL (basal = 0,9 mg/dL). Em um seguimento de 2 anos, o paciente permaneceu fora da diálise com doença renal crônica avançada (DRC) (estágio IIIb). O paciente de 87 anos apresentava IRA grave com creatinina sérica em 10,41 mg/dL (valor basal de = 2,27 mg/dL). O paciente necessitou de hemodiálise e foi tratado com esteroides, rituximabe e plasmaferese. Infelizmente, o paciente desenvolveu bacteremia induzida por cateter e, posteriormente, evoluiu a óbito por sepse. A hidralazina pode causar IRA grave, resultando em DRC ou óbito. Dado este perfil de eventos adversos extremamente desfavorável e a disponibilidade generalizada de agentes anti-hipertensivos alternativos, o uso de hidralazina deve ser considerado com muita parcimônia.

Daño hepatocelular, proteinuria y autoinmunidad: ¿enfermedad multisistémica o coincidencia de enfermedades? Caso clínico / Hepatocellular damage, proteinuria and autoimmunity: multisystemic disorder or coexistence of diseases?

We report a 19 years old male presenting with knee pain, elevated liver enzymes and proteinuria. Further investigation found positive antinuclear and anti-smooth muscle antibodies and a liver biopsy revealed the presence of an autoimmune hepatitis. Treatment with corticosteroids and azathioprine was started, resulting in normalization of liver enzymes but proteinuria persisted and a kidney biopsy disclosed a focal segmental glomerulosclerosis. The use of lisinopril resulted in a significative reduction of proteinuria and, after 30 months of follow up, he continues with azathioprine, lisinopril and a low prednisone dose without evidence of liver or kidney disease activity.

Pathogenic factors research in focal segmental glomerulosclerosis / 中国医师进修杂志

Focal segmental glomerulosclerosis is a type of glomerulopathy, which is named after the pathological characteristics of kidney. It is an important part of glomerular disease, and also a common chronic kidney disease in clinical practice.A number of epidemiological studies have shown that the incidence of FSGS has increased year by year and its prognosis is not satisfying. At present, there is still a lack of comprehensive understanding of the occurrence and development of FSGS. This article summarizes the important findings from the research and exploration of FSGS pathogenic factors in recent years in order to provide reference value for the diagnosis and treatment of FSGS.

Histopathological analysis of the non - tumour parenchyma following radical nephrectomy: can it predict renal functional outcome?

ABSTRACT Introduction Radical nephrectomy (RN), a recommended treatment option for patients with Renal cell carcinoma (RCC) leads to an inevitable decline in global renal function. Pathological changes in the non-tumour parenchyma of the kidney may help predict the function of the remaining kidney. Materials and Methods Aim of this prospective, observational study was to find histopathological factors in the non-tumor renal parenchyma that could predict the decline in global renal function postoperatively and its association with co-morbidities like diabetes (DM). Data of consecutive patients undergoing RN from December-2013 to January-2015 was collected. Non-tumor parenchyma of the specimen was reported by a dedicated histopathologist. eGFR was calculated using Cockcroft-Gault formula before the surgery and at last follow up of at least 12 months. Results 73 RN specimens were analyzed. Mean follow up was 12.3 months. The mean decrease in eGFR was 22% (p=.0001). Percent decrease in eGFR did not show association with any of the histopathological parameters studied. DM was significantly associated with decrease in percent eGFR (p<0.05) and increase in arteriolar hyalinosis (p=0.004), Glomerulosclerosis (p=0.03) and Interstitial fibrosis/ Tubular atrophy (p=.0001). Maximum size of the tumor showed a negative correlation with percentage change in eGFR (p=.028). Conclusion Histological parameters in the non-tumour portion of the RN specimen may not be able to predict renal function outcome over a short follow up. However, presence of DM was associated with adverse pathological changes and significant decrease in renal function postoperatively.

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

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

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

Síndrome nefrótico resistente a corticoides en pediatría, actualización / Steroid-resistant nephrotic syndrome in pediatrics, an update

El síndrome nefrótico (SN) constituye la glomerulopatía más frecuente en pediatría. El pilar del tratamiento con-tinúa siendo la terapia con corticoides. Dependiendo de la respuesta se clasifica en síndrome nefrótico corti-coresistente (SNCR) y corticosensible. La mayoría de los pacientes con SNCR tienen glomeruloesclerosis focal y segmentaria, asociada con 50% de riesgo de enfermedad renal terminal, por lo que se recomienda biopsia renal. Es importante realizar pruebas genéticas, ya que ciertas mutaciones resultan en corticorresistencia, siendo la mutación del gen NPHS2 (podocina) la más relacionada. Este artículo es una revisión de la literatura mundial y nacional acerca del SNCR en pediatría, enfatizando en nuevos enfoques de diagnóstico y tratamiento

Nephrotic syndrome (NS) is the most frequent glomerulopathy in pediatrics. The mainstay of treatment continues to be corticosteroid therapy. Depending on the response, it is classified as corticosteroid nephrotic syndrome (SNCR) and corticosensitive syndrome. Most patients with SNCR have focal and segmental glomerulosclerosis, associated with a 50% risk of end-stage renal disease, and renal biopsy is recommended. It is important to perform genetic tests, since certain mutations result in corticoresistance, with the mutation of NPHS2 gene (podocin) being the most related. This article is a review of the global and national literature on SNCR in pediatrics, emphasizing new approaches to diagnosis and treatment.

Mice with focal segmental glomerular sclerosis are induced by adriamycin and its mechanism / 中华肾脏病杂志

Objective To establish adriamycin-induced focal segmental glomerular sclerosis(FSGS) mice model,and observe the expressions of and relation between oxidative stress and p38 MAPK signal pathway in renal injury.Methods Eight-week-old male Balb/c mice were randomly divided into FSGS group (n=20) and control group (n=20).In FSGS group mice were intravenously injected with a single dose of adriamycin (0.01 rag/g),and mice in control group were received saline with the same dose.At day 3,7,14,22 and 32,urine protein-to-urine creatinine ratio (P/C) was detected.At day 22 and 32,serum creatinine,blood urea nitrogen,nitric oxide (NO) and reactive oxygen species (ROS) in blood and urine,and ROS in kidney tissues were detected;changes of pathological morphology in renal tissue were analyzed by HE stain;the expressions of NF-κB,CD36,IL-13,BAX and Bcl-2 mRNA were detected by real time quantitative PCR;the expressions of NF-κB,p-p38 and p-ERK1/2 protein were detected by Western blotting.Results Compared with that in control group,P/C was gradually increasing in FSGS group,and peaked at day 22 (P ＜ 0.05).At day 22 and 32,mice had higher creatinine,serum creatinine,urea nitrogen,ROS and NO in FSGS group than those in control group (all P ＜ 0.05).There were mild hyperplasia of mesangial cells and mesangial matrix,segment with moderate exacerbations,podocytes with significant proliferation,and the capillary loops of the stenosed in the glomerular in FSGS group at day 32.Compared with those in control group,the mRNA expression of NF-κB,BAX,IL-13 and CD36,and the protein expressions of NF-κB and p-p38 MAPK were gradually increased in FSGS group,all showed statistical differences at day 32 (all P＜ 0.05);the expression of p-ERK1/2 was increased at day 22 (P ＜ 0.05) but was reduced at day 32 (P ＜ 0.05).Conclusions Adriamycin has induced FSGS in mice successfully,which may through oxidative stress activating p38,up-regulating NF-κB,increasing the inflammatory cytokines and inducing apoptosis pathways.

Aberrant Blood Vessel Formation Connecting the Glomerular Capillary Tuft and the Interstitium Is a Characteristic Feature of Focal Segmental Glomerulosclerosis-like IgA Nephropathy

BACKGROUND: Segmental glomerulosclerosis without significant mesangial or endocapillary proliferation is rarely seen in IgA nephropathy (IgAN), which simulates idiopathic focal segmental glomerulosclerosis (FSGS). We recently recognized aberrant blood vessels running through the adhesion sites of sclerosed tufts and Bowman's capsule in IgAN cases with mild glomerular histologic change. METHODS: To characterize aberrant blood vessels in relation to segmental sclerosis, we retrospectively reviewed the clinical and histologic features of 51 cases of FSGS-like IgAN and compared them with 51 age and gender-matched idiopathic FSGS cases. RESULTS: In FSGS-like IgAN, aberrant blood vessel formation was observed in 15.7% of cases, 1.0% of the total glomeruli, and 7.3% of the segmentally sclerosed glomeruli, significantly more frequently than in the idiopathic FSGS cases (p = .009). Aberrant blood vessels occasionally accompanied mild cellular proliferation surrounding penetrating neovessels. Clinically, all FSGS-like IgAN cases had hematuria; however, nephrotic range proteinuria was significantly less frequent than idiopathic FSGS. CONCLUSIONS: Aberrant blood vessels in IgAN are related to glomerular capillary injury and may indicate abnormal repair processes in IgAN.

Doença de lesões mínimas e glomeruloesclerose segmentar e focal em adultos: resposta a corticoide e risco de insuficiência renal / Minimal change disease and focal segmental glomerulosclerosis in adults: response to steroids and risk of renal failure

Resumo Introdução: O perfil clínico de pacientes brasileiros adultos com síndrome nefrótica por doença de lesões mínimas (LM) e glomeruloesclerose segmentar e focal (GESF) é pouco conhecido. Objetivo: Avaliamos as características clínico-laboratoriais e resposta a tratamento em pacientes adultos com síndrome nefrótica e diagnósticos histológicos de LM ou GESF. Métodos: Fez-se a análise retrospectiva de 50 pacientes adultos com LM e 120 com GESF. Todos os pacientes foram inicialmente tratados com corticosteroide. Os desfechos do estudo foram: resposta a corticosteroide, prevalência de remissão total, progressão para doença renal crônica estágio 5 (DRC5) e necessidade de terapia de substituição renal por DRC5. Resultados: Níveis iniciais de creatinina sérica foram 24% mais elevados entre pacientes com GESF (p = 0,02) e os de proteinúria foram 36% mais altos em LM (p < 0,001). Pacientes com LM foram córtico-sensíveis em 80% dos casos, com remissão total em 74%, e os pacientes com GESF em 58% (p = 0,01), com remissão total em 30% (p = 0,002). A prevalência de insuficiência renal aguda em pacientes com GESF foi de 39% (vs. 12%, p = 0,013) e DRC5 de 10% (vs. 0%, p < 0,001). Remissão completa ou parcial com o uso de corticosteroide reduziu em 83% o risco de DRC5 (p < 0,001) e remissão total associou-se a redução no risco de DRC5 de 89% (p < 0,001). Conclusão: A resposta positiva à corticoterapia foi o fator mais importante relacionado à preservação da função renal ao longo de mais de uma década de seguimento, e GESF relacionou-se a menor índice de resposta a corticosteroide.

Abstract Introduction: There is scarce data on the clinical profile of adult Brazilian patients with nephrotic syndrome caused by minimal change disease (MCD) and focal segmental glomerulosclerosis. Objective: We evaluated the clinical characteristics and response to treatment in adult patients with nephrotic syndrome having a histological diagnosis of MCD or FSGS. Methods: This is a retrospective analysis of 50 patients with MCD and 120 with FSGS. All patients were initially treated with steroids. The study outcomes were: steroid responsiveness, prevalence of total remission, progression to chronic renal failure and need of renal replacement therapy due to end-stage renal disease (ESRD). Results: Initial serum creatinine level was 24% higher among patients with FSGS (p = 0.02), and proteinuria levels were 36% higher in MCD (p < 0.001). Patients with MCD were sensitive to steroid therapy in 80% of the cases, with total remission in 74%, while patients with FSGS were sensitive in 58% (p = 0.01), with total remission in 30% (p = 0.002). Patients with FSGS had an acute renal failure prevalence of 39% (vs. 12%, p = 0.013) and ESRD of 10% (vs. 0%, p < 0.001). Steroid responsiveness reduced in 83% the risk of ESRD (p < 0.001), while total remission was associated to a reduction in risk of 89% (p < 0.001). Conclusion: A positive response to steroid therapy was the most important factor related with preservation of renal function and FSGS was related with less steroid responsiveness.

Glomeruloesclerose segmentar e focal (GESF) colapsante associada ao parvovírus B19: relato de caso / Collapsing variant of focal segmental glomerulosclerosis by parvovirus B19: case report

Objetivo: Descrever quadro clínico-laboratorial de glomeruloesclerose segmentar e focal (GESF) subtipo colapsante em associação com infecção por parvovírus B19 (PVB19). Relato do caso: Paciente feminino, 37 anos, parda, iniciou quadro de faringoalgia e febre aferida com melhora parcial após penicilina. Com uma semana, observou redução de débito urinário e edema de membros inferiores. Tabagista, com histórico familiar e pessoal negativos para hipertensão, diabetes ou nefropatias. À admissão, apresentava-se com oliguria, hipertensão e edema, associados à anemia microcítica e hipocrômica hipoproliferativa, proteinúria nefrótica, hematúria microscópica e alteração da função renal. A investigação reumatológica e sorologias para hepatites e HIV foram negativas. Ultrassonografia de rins e vias urinárias sem alterações. PCR foi positivo para PVB19 em aspirado de medula óssea e sangue. A biópsia renal conclusiva de GESF subtipo colapsante. Ocorreu remissão espontânea com duas semanas do quadro. Em retorno ambulatorial, o PCR em sangue periférico foi negativo para PVB19, sugerindo associação de GESF colapsante a fase aguda ou reativação da infecção viral. Conclusão : Este relato registra a associação temporal entre GESF colapsante e viremia pelo PVB19, seja por infecção aguda ou reativação de infecção latente. A associação GESF colapsante e PVB19 é descrita na literatura, com demonstração da presença do vírus em tecido renal, porém, a real relação do vírus na patogênese dessa glomerulopatia permanece indefinida. .

Objective: To describe the clinical and laboratory profile of focal segmental glomerulosclerosis (FSGS) of the collapsing subtype in association with infection by parvovirus B19 (PVB19). Case report: Female patient, 37 years old, mulatto, developed pharyngalgia and fever with partial improvement after penicillin. After one week we observed reduced urinary output and lower limb edema. Smoker, family and personal history negative for hypertension, diabetes or kidney disease. Patient presented with olyguria, hypertension and edema, also hypochromic microcytic hypoproliferative anemia, nephritic range proteinuria, microscopic hematuria and renal dysfunction. All rheumatologic investigation, HIV and hepatitis serology were negative. Unremarkable renal ultrasound. PCR positive for PVB19 in bone marrow aspirate and blood and renal biopsy conclusive of collapsing FSGS subtype. Spontaneous remission occurred within two weeks of the profile. The blood PVB19 PCR was repeated within a month and resulted negative. This finding demonstrated PVB19 acute infection or viral reactivation in association with collapsing FSGS. Conclusion: There is demonstrated the temporal association of PVB19 viremia and collapsing FSGS, due primary infection or viral reactivation. The association of collapsing FSGS and PVB19 is described in the literature, demonstrating virus presence in kidney tissue, but the real relationship of virus in the pathogenesis of this glomerulopathy remains unclear. .

Expression change of NALP3/ASC/caspase-1 in renal tissues of FSGS / 重庆医学

Objective To investigate the expression change of renal NLR family pyrin domain containing-3 protein(NALP3) in-flammasome in the nephrotic syndrome(NS) patients with focal segmental glomerulosclerosis(FSGS) and its relation with the tubu-lointerstitial pathogenic injury degree ,expression of inflammatory factors and clinical biochemical indexes .Methods Immunohisto-chemistry was used to detect the expressions of NALP3/ASC/caspase-1 and their downstream effector molecule IL-1β,IL-18 in re-nal tubular epithelial cells .The tubulointerstitial injury score and the activated macrophages F4/80 in renal interstitium of the FSGS patients and NS patiens were evaluated .The serum creatinine ,urea ,total protein ,albumin ,24 h urine protein and estimated glomer-ular filtration rate(eGFR) were observed .The correlation of tubulointerstitial injury with NALP3/ASC/caspase-1 ,IL-1β,IL-18 were respectively analyzed .Results The expression of NALP3/ASC/caspase-1 ,IL-1β,IL-18 in the renal tissue of the FSGS pa-tients was significantly increased compared with that in the control group (P<0 .01) .NALP3/ASC/capspase-1 expression was pos-itively correlated with the expression of IL-1β,IL-18(P< 0 .01) .NALP3/ASC/caspase-1 ,IL-1β,IL-18 expression was positively correlated with renal tubulointerstitial injury and the F4/80 expression intensity(P<0 .01) .NALP3/ASC/caspase-1 ,IL-1β,IL-18 was significantly positively correlated with 24 h urine protein and Scr ,and negatively correlated with the eGFR (P<0 .05) ,but had no obvious correlation with plasma urea ,plasma total protein and albumin concentrations .Conclusion The NALP3 inflammasome might participate in the pathogenic mechanism of FSGS through the activation of its downstream inflammatory factor of IL-1β,IL-18 ,the more higher its expression degree ,the more severe the renal tissue injury ,whether which could be served as the warning in-dex needs the further clinical verification .

Effects of pretransplant plasmapheresis and rituximab on recurrence of focal segmental glomerulosclerosis in adult renal transplant recipients

BACKGROUND/AIMS: Recurrent focal segmental glomerulosclerosis (FSGS) following renal transplantation is relatively common. However, the risk factors and optimal pretransplant treatment preventing recurrence of FSGS remain controversial. METHODS: We retrospectively reviewed 27 adult renal transplant recipients with FSGS over a period of 10 years. We first compared possible risk factors for FSGS recurrence between the recurrence and nonrecurrence groups. Then we evaluated the effect of pretransplant plasmapheresis (PP; n = 4) and PP with rituximab (PP + RTX; n = 5) on recurrence of FSGS after transplantation compared to control patients that were not treated with these modalities. RESULTS: There were seven recurrences in 27 patients (25.9%), but there were no significant differences in possible risk factors for FSGS recurrence between the two groups. Recurrence rates between patients with pretransplant PP or PP + RTX and control patients were not significantly different (22.2% vs. 27.7%, p > 0.05). There was also no significant difference in recurrence between the pretransplant PP and PP + RTX groups (25% vs. 20%, p > 0.05). CONCLUSIONS: Pretransplant PP or PP + RTX do not significantly decrease the recurrence of FSGS in adult renal transplant candidates.