Abstract Acute disseminated encephalomyelitis (ADEM) is an acute demyelinating disorder of the central nervous system. ADEM should be suspected when a patient develops multifocal neurologic abnormalities with encephalopathy, especially if occurring after a viral infection or immunization. In this study, the authors describe two cases of ADEM with positive anti-myelin oligodendrocyte glycoprotein (MOG) antibodies requiring hospitalization in a Pediatric Intensive Care Unit and plasmapheresis treatment.

Resumo A encefalomielite aguda disseminada (ADEM) é uma doença desmielinizante aguda do sistema nervoso central. O diagnóstico de ADEM deve ser considerado quando o doente apresenta alterações neurológicas focais associadas a encefalopatia, sobretudo se as manifestações surgem após uma infeção vírica ou vacinação. Neste artigo, são descritos dois casos clínicos de ADEM com anticorpos anti-MOG positivos com necessidade de internamento em Unidade de Cuidados Intensivos Pediátricos e tratamento com plasmaferese.

ABSTRACT Objective: Permanent access in the form of a fistula is the preferred form of vascular access for most pediatric patients on maintenance hemodialysis (HD) therapy; however, the technical aspects of the procedure that are unique to the pediatric population, the expectation of a short waiting time for kidney transplantation and the need to cannulate every other day (with the pain and fear associated with it) limit its use. Our objective was to analyze the long-term outcomes of pediatric arteriovenous fistulas in our institution. Methods: A retrospective review was performed of all arteriovenous fistula (AVF) created in a HD population aged 0 to 18 years at a single institution from 2007 to 2019. Data abstracted included age, weight, etiology of renal failure, time on dialysis, central venous catheter history and transplantation history. Data were analyzed to determine the primary and secondary patency. Results: During the study period, 19 AVFs were performed in 16 patients, of whom 9 patients (56.3%) were male. Mean patient age was 12.3 years (range 5-17 years), and mean weight was 38.3kg (range 12-83kg). At the time of AVF creation, 9 patients were on dialysis and 7 patients had a central venous catheter (CVC), with a median length of CVC dependence of 10 months. Procedures performed included 4 radiocephalic fistulas, 11 brachiocephalic fistulas and 4 brachiobasilic. Five accesses failed to mature (26.3%). Mean follow-up was 6 years. The 2-year primary and secondary patency rates were 92.3% and 100%, respectively. The 4-year primary and secondary patency rates were 76.9% and 100%, respectively. No thrombosis was documented during follow-up. During the postoperative period, 10 patients (62.5%) received a kidney transplant, in a mean time of 23 months. Conclusions: AVFs demonstrate excellent long-term patency in pediatric HD patients. No significant complications were reported and no thrombosis occurred.

É descrito o caso clínico de uma adolescente de 16 anos diagnosticada com hemovítreo e hemangioblastoma da retina em contexto de urgência por perda súbita de visão. O estudo por ressonância magnética encefálica e pélvica evidenciou a presença de hemangioblastomas cerebelosos e lesões nodulares renais de natureza neoplásica suspeita. A doente foi submetida a nefrectomia parcial do rim esquerdo e o exame histológico confirmou o diagnóstico de carcinoma papilar de células renais com predomínio de células claras. O diagnóstico clínico de doença de Von Hippel-Lindau (VHL) foi confirmado por estudo genético. A doença de VHL é uma síndrome hereditária autossómica dominante de neoplasias múltiplas causada por mutações germinativas no gene supressor tumoral VHL. Os doentes apresentam predisposição para o desenvolvimento de quistos e neoplasias hipervascularizadas, sendo as mais comuns hemangioblastomas do sistema nervoso central (SNC) e da retina, quistos e carcinomas de células renais e feocromocitomas. A suspeita de diagnóstico de doença de VHL deve ser considerada se um indivíduo com antecedentes familiares de VHL apresentar uma lesão característica da doença ou, em ausência de história familiar de VHL, dois hemangioblastomas do SNC e/ou retina ou um hemangioblastoma do SNC ou da retina associado a carcinoma de células renais, feocromocitoma, quistos ou tumor endócrino pancreáticos ou cistadenoma do epidídimo. A imagiologia tem um papel importante nesta condição, através do diagnóstico de anomalias, seguimento e rastreio de portadores assintomáticos.

Here in is reported the case of a 16-year-old female diagnosed with vitreous haemorrhage and hemangioblastoma of the retina, referred to the Emergency Department due to sudden vision loss. Brain and pelvic magnetic resonance imaging showed cerebellar hemangioblastomas and renal nodular lesions of suspicious nature. The patient was submitted to partial left nephrectomy and histological examination revealed papillary renal cell carcinoma with clear-cell predominance. Clinical diagnosis of Von Hippel-Lindau (VHL) disease was confirmed by genetic study. VHL disease is a hereditary, autosomal dominant syndrome of multiple neoplasms caused by germline mutations in VHL tumor-suppressor gene. Patients are predisposed to development of cysts and hypervascular neoplasms, the most common being hemangioblastomas of the central nervous system (CNS) and retina, cysts and renal cell carcinomas, and pheochromocytomas. VHL diagnosis should be suspected if an individual with family history of VHL presents with a characteristic disease lesion or, in absence of family history of VHL, with two CNS and/or retinal hemangioblastomas or a CNS/retinal hemangioblastoma associated with renal cell carcinoma, pheochromocytoma, pancreatic cysts or endocrine tumor, or epididymal cystadenoma. In VHL disease, imaging plays a key role in detection of abnormalities, follow-up, and screening of asymptomatic mutated gene carriers.

Introdução: O rituximab pode ser uma arma terapêutica útil no tratamento da sindroma nefrótica complicada, permitindo a redução de inibidores da calcineurina e de corticóides. Métodos: Estudo retrospetivo de todas as crianças que receberam rituximab no tratamento de sindroma nefrótica num hospital terciário. Todos os doentes, exceto um (dose única), receberam quatro infusões de rituximab 375mg/m2 com intervalo de uma semana, tendo um seguimento mínimo de quatro meses e máximo de 118 meses. Resultados: Foram incluídos 11 doentes, três com sindroma nefrótica corticorresistente e oito com sindroma nefrótica corticodependente ou multirrecidivante. A relação masculino:feminino foi de 8:3, com idade mediana no quadro inaugural de 2,7 anos (mínimo 1,7 - máximo 9,9). Todos os doentes foram tratados previamente com inibidores da calcineurina, oito com ciclofosfamida e sete com micofenolato de mofetil. Dois doentes não responderam, evoluindo para a doença renal crónica estádio 5. Registou-se uma mediana de três episódios de recidiva nos seis meses pré-rituximab e nenhuma recidiva nos seis meses pós-rituximab (p=0.013). Foi possível reduzir significativamente a dose de corticóides (p=0.001). Dois doentes recidivaram aos 9 e 12 meses pós-rituximab. Um outro doente recidivou imediatamente após transplante renal. Verificou-se recuperação da contagem de células CD19 em seis doentes, incluindo dois recidivantes. Não se reportou nenhum caso de infeção severa ou neoplasia. Conclusão: O rituximab reduziu significativamente o número de recidivas e a dose de corticóides na sindroma nefrótica complicada. A recuperação da contagem de células CD19 não previu a recidiva, mas pode indicar a necessidade de doses adicionais de rituximab.

Background: In children with idiopathic nephrotic syndrome, rituximab can maintain short-term remission allowing steroids and calcineurin inhibitors taper. Methods: We retrospectively reviewed all children receiving rituximab for idiopathic nephrotic syndrome at a tertiary hospital. All patients, except one who received a single dose, had four infusions of 375mg/m2 of rituximab at a one-week interval, minimum follow-up duration of four and maximum 118 months. Results: Eleven patients were included, three patients with steroid resistant nephrotic syndrome and eight steroid dependent or frequently relapsing nephrotic syndrome. Male:female ratio was 8:3 and median age at onset was 2.7 (minimum 1.7-maximum 9.9) years-old. All patients received a trial of calcineurin inhibitors, eight received cyclophosphamide and seven mycophenolate mofetil. Remission of proteinuria was observed in nine patients. Two patients were non-responders evolving to end-stage renal disease. Patients experienced in median three relapses during the six months preceding rituximab. Responders did not relapse in the following six months (p=0.013) and daily dose of prednisolone was significantly reduced (p=0.001). Two patients relapsed at 9 and 12 months after rituximab. Another patient experienced relapse immediately after kidney transplant, successfully treated with our protocol for focal and segmental glomerulosclerosis relapse. Recovery of CD19 cells counting was observed in six patients including two relapsing patients. No severe infection or neoplasia were reported. Conclusions: Rituximab successfully reduced relapsing in complicated idiopathic nephrotic syndrome, steroid dose and enabled other immunosuppressants weaning off in most patients. Recovery of CD19 cells did not anticipate relapse, but may herald the need for additional rituximab infusions.

A Síndrome de Nutcracker (SN) resulta da compressão da veia renal esquerda ao longo do seu trajeto, na maioria dos casos entre a aorta e a artéria mesentérica superior ou, menos frequentemente, entre a aorta e a coluna lombar. Apesar de na maioria dos casos ser assintomática, constitui uma causa rara de hematúria. Descreve-se o caso de um adolescente de 11 anos referenciado à consulta de Nefrologia Pediátrica por hematúria macroscópica com dois meses de evolução, associada a anemia sem repercussão hemodinâmica. Após investigação, concluiu tratar-se de uma hematúria não glomerular, de origem extra-renal. A ecografia abdominal e renal com Doppler não revelou alterações. A angiotomografia computorizada abdominopélvica, após cuidadosa análise, revelou a presença de SN. Por hematúria persistente com necessidade de suporte transfusional, aos 13 anos foi submetido a autotransplante renal. O diagnóstico da SN é essencialmente clínico, imagiológico e necessariamente de exclusão. A orientação terapêutica deve ser individualizada e requer uma abordagem multifatorial.

The Nutcracker Syndrome (NS) originates from the compression of the left renal vein in its trajectory, mostly between the aorta and the superior mesenteric artery, or less frequently between the aorta and the lumbar spine. Although asymptomatic in most cases, it can be a rare cause of hematuria. We present the case of an 11-year-old male adolescent who was referred to a Pediatric Nephrology evaluation for a two-month-long gross hematuria. The patient also had anemia without hemodynamic repercussion. After the initial work-up, it was concluded to be a non-glomerular, extra-renal hematuria. Abdominal and renal ultrasound with Doppler was normal. The abdominal and pelvic computerized angiotomography revealed, after a careful examination, the presence of NS. Due to persistent gross hematuria with the need for transfusional support, at the age 13, the patient underwent a renal autotransplantation. The diagnosis of NS is essentially clinical, imagiological and necessarily a diagnosis of exclusion. The treatment must be individualized and requires a multifactorial approach.

Introdução: A insuficiência renal crónica terminal está associada a numerosas comorbilidades e a um aumento do risco de mortalidade cerca de 30 vezes superior à população pediátrica geral. O primeiro transplante renal bem sucedido em crianças foi realizado em 1954. Os progressos cirúrgicos e as novas terapêuticas imunossupressoras aumentaram a sobrevida dos doentes e do enxerto renal nos últimos anos. Objectivos: Avaliação da experiência em transplantação renal em idade pediátrica do Centro Hospitalar do Porto nos últimos 30 anos. Métodos: Estudo retrospetivo dos dados epidemiológicos e clínicos dos doentes pediátricos transplantados entre Janeiro de 1984 e Agosto 2013. Foi feita a análise da evolução temporal da atividade de transplantação através da comparação da sobrevida do enxerto por décadas de transplantação (1984-89 / 1990-99 / 2000-09 / 2010-13). Foi também comparada a sobrevida do enxerto em dois grupos etários (0-10 anos ; 11-17 anos) à data da transplantação. Resultados: Cento e trinta e nove doentes (58.3% - sexo masculino) foram submetidos a 147 transplantes renais (6.8% de dador vivo). As anomalias congénitas do rim e trato urinário (56.5%) e as glomerulonefrites (18.4%) foram as causas principais de insuficiência renal. A sobrevida do enxerto não censurada aos 5, 10, 15 e 20 anos foi 84.7%, 71.1%, 60.0% e 51.0% e a sobrevida do doente aos 5, 10, 15 e 20 anos foi 97.9%, 95.9%, 94.7% e 94.7%, respetivamente. A sobrevida do enxerto aumentou ao longo do tempo e a diferença entre as décadas foi estatisticamente significativa (p=0.004). Apesar da melhor sobrevida no grupo com idade superior a 11 anos, a diferença da sobrevida do enxerto entre os grupos etários não foi estatisticamente significativa (p=0.697). Conclusão: Os resultados do Centro Hospitalar do Porto são comparáveis aos dos grandes centros de transplantação renal pediátrica. Observou-se uma melhoria dos resultados ao longo dos anos na nossa Unidade. A existência de um rigoroso processo de acompanhamento poderá ter ajudado a minimizar o impacto negativo da adolescência na sobrevida do enxerto.

Introduction: End-stage renal disease in children is associated with numerous comorbidities and with age-specific mortality rates approximately 30 times higher than in healthy children. The first kidney transplantation in children was performed successfully in 1954. Surgical advances and new immunosuppressive medications have greatly improved patient’s and graft’s survival in the last years. Aim: Report Centro Hospitalar do Porto experience in pediatric renal transplantation in the last 30 years. Methods: Epidemiological and clinical data of all patients younger than 18 years, transplanted between January 1984 and August 2013, were collected from our database. In order to analyze the transplantation outcome in our center we compare graft survival between decades (1984-89 / 1990-99 / 2000-09 / 2010-13). We also compare graft survival between two age groups of patients (0-10 years ; 11-17 years) at the time of surgery. Results: One hundred thirty-nine patients (58.3% male) underwent 147 renal transplants (6.8% live donors). Congenital anomalies of the kidney and urinary tract (56.5%) and glomerulonephritis (18.4%) were the major causes of renal disease. Uncensored graft survivals rates at 5, 10, 15 and 20 years were 84.7%, 71.1%, 60.0% and 51.0%, while patient survivals were 97.9%, 95.9%, 94.7% and 94.7% respectively. Graft survival improved over time and the difference between the decades was statistically significant (p=0.004). Despite the better survival in the group of patients older than 11 years, graft’s survival difference between the two age groups was not statistically significant (p=0.697). Conclusion: The results of our hospital are comparable to other international centers. Significant improvement in survival was observed over the time. It seems that an accurate follow-up of our patients helps to minimize the negative impact of adolescence on graft survival rates.

Tenofovirrenal toxicity, particularly when associated with other antiretrovirals, has been reported in the adult HIV-positive population. Reports in HIVpositive children are very rare. The authors report a paediatric case of nephrotoxicity associated with tenofovir and didanosine, emtricitabine and lopinavirritonavir coadministration. A 12-year-old girl with AIDS (clinical stage C) with a multidrug-resistant virus and several treatment failures initiated emtricitabine, tenofovir, didanosine and lopinavir-ritonavir in 2008 with good tolerance. Her viral load became undetectable and CD4 count normal. Two years later she presented generalized weakness, polydipsia and polyuria. On physical examination dehydration was evident. Her vital signs were stable. She had lost 5% of her body weight in the previous week. Urinalysis revealed a urine gravity of 1000, osmolality 150 mOsm/Kg and no proteinuria or glucosuria. Blood analysis showed osmolality 289 mOsm/Kg, normal values of glucose, creatinine, urea, sodium, potassium, chloride and calcium. A water restriction test followed by desmopressin administration confirmed the diagnosis of nephrogenic diabetes insipidus. Tenofovir and didanosine were stopped and abacavir was added. The patient was treated with a thiazide diuretic and salt restriction. There was good clinical evolution and no relapses. This case highlights important possible side effects of tenofovir and emphasises the need for further studies into the renal safety of this agent in paediatric patients.

Atypical haemolytic uraemic syndrome is caused by alternative complement pathway dysregulation. It has recently been recognised that most cases are due to genetic factors and a growing list of mutations has been described. Atypical haemolytic uraemic syndrome is associated with a dismal prognosis, a relapsing course, high acute mortality and frequent progression to end-stage renal disease. We describe a five-year-old boy admitted with a first recurrence of atypical haemolytic uraemic syndrome. The primary onset of the disease was at 15 months of age, following which there was complete recovery of haematological and renal parameters. His family history was significant in that his mother had died at the age of only 23 years of a stroke with associated thrombotic microangiopathy, suggesting a familial form of the disease. Sequencing of the gene encoding complement factor H revealed a heterozygous SCR20 mutation (3644G>T, Arg1215Leu), confirming the diagnosis. The patient was successfully treated with fresh frozen plasma infusions that induced disease remission. We also review currently evolving concepts about atypical haemolytic uraemic syndrome caused by factor H mutation, its diagnosis, the role of genetic testing and management strategies in children.

Introdução: As crianças com síndrome nefrótico (SN) têm um risco aumentado de complicações tromboembólicas. Caso clínico: Adolescente de 12 anos, sexo masculino, com síndrome nefrótico corticorresistente, medicado com prednisolona, ciclosporina, omeprazol, enalapril e ácido acetilsalicílico. Internado por quadro clínico de anasarca e oligúria com boa resposta clínica inicial à perfusão diária de albumina. Ao quarto dia de internamento iniciou febre, toracalgia, expectoração hemoptoica e agravamento da dispneia. Realizou angiografia pulmonar por tomografia computorizada que demonstrou tromboembolismo pulmonar agudo central e periférico, com múltiplas áreas de enfarte pulmonar e derrame pleural de pequeno volume. O rastreio de trombofilias hereditárias demonstrou heterozigotia para a mutação G20210A do gene da protrombina e homozigotia para a variante termolábil C677T do gene da metilenotetrahidrofolato reductase. Conclusão: As complicações tromboembólicas nas crianças com SN são raras e o seu diagnóstico implica um elevado índice de suspeição. O rastreio da trombofilia hereditária é importante na identificação de doentes com síndrome nefrótico com risco trombótico acrescido.

Introduction: Children with nephrotic syndrome (NS) have an increased risk of thromboembolic complications. Case report: The authors report a case of 12 year-old boy with steroid resistant nephrotic syndrome, treated with prednisone, cyclosporine, omeprazole, enalapril and acetylsalicylic acid. He was admitted for anasarca and poor renal perfusion, with initial good response to daily albumin infusions. By the fourth day of hospitalization he presented fever, chest pain, hemoptysis and worsening of dyspnea. Computed tomography pulmonary angiography showed central and peripheral acute pulmonary thromboembolism, with multiple areas of pulmonary infarction and pleural effusion of small volume. Screening for hereditary thrombophilia showed heterozygosity for the G20210A mutation in prothrombin gene and homozygosity for the thermolabile variant C677T of the methylenetetrahydrofolate reductase. Conclusion: The thromboembolic complications in children with NS are rare and its diagnosis requires a high index of suspicion. Screening for inherited thrombophilia is important to identify patients with NS and increased thrombotic risk.