Diagnóstico Pré-Natal de Uropatia: Importância do Desenvolvimento Embriológico Renal

As uropatias malformativas constituem a principalcausa de anomalia neonatal nao letal. Estas anomalias do desenvolvimento devem ser interpretadas com base no conhecimento da morbilidade e, em alguns casos, a mortalidade associada a este tipo de patologia 1,2. As malformações congénitas devem ser pensadas com base no conhecimento da dinâmica do normal desenvolvimento embrionário e dos múltiplos factores reguladores intervenientes, so assim será possivel estabelecer estratégias eficazes de investigação e terapêutica

Hypertension as An Atypical Presentation of Unilateral Ureteral Obstruction

Ureteral obstruction (ureteropelvic or ureterovesical junction obstruction) is frequently diagnosed during the workup investigation of an asymptomatic infant or child with upper urinary tract dilatation, commonly identified in a prenatal ultrasound. In older children, recurrent lumbar pain is a red flag for ureteral obstruction. Although less frequent, hypertension may be the initial and only manifestation of ureteral obstruction. The authors present two pediatric cases of unilateral ureteral obstruction with hypertension, in which the surgical treatment of the obstruction leads to blood pressure normalisation. In all pediatric age groups, a systematic investigation for secondary causes of hypertension is of paramount importance. In some cases, especially those of an obstructive nature, early surgical management can be curative, with normalization of blood pressure levels and prevention of renal injury.info:eu-repo/semantics/publishedVersio

Fanconi Syndrome after Ifosfamide Exposure

ntroduction: Ifosfamide is an antineoplastic drug frequently used in the treatment of pediatric malignancies. However it is responsible for nephrotoxicity in up to 30% of patients, which can be manifested from asymptomatic tubulopathy to overt renal failure. We report a case of a patient who developed Fancony syndrome after exposure to ifosfamide. Clinical Case: A two-year-old caucasian boy was diagnosed with stage IV Burkitt lymphoma with hepatic and renal involvement without central nervous system (CNS) invasion. Baseline evaluation showed GFR of 60 mL/min per 1.73 m2 (Shwartz formula, k=0.143). He underwent five cycles of chemotherapy involving cyclophosphamide, vincristine, prednisolone, doxorubicin, methotrexate and cytarabine. The patient was in remission but three months later relapsed with evidence of involvement of the liver and kidneys on CT. Another course of chemotherapy was initiated with ifosfamide, carboplatin, etoposide, rituximab (R-ICE) and intratecal administration of methotrexate and aracitabine. After five cycles of R-ICE, the patient had a bone marrow transplant. According to protocol, busulfan, cyclophosphamide, tacrolimus, methotrexate, fluconazole and acyclovir were administered. No immediate complications were registered. Four months after transplant, the patient showed significant downward growth percentile crossing and urinalysis suggested tubulopathy. Upon nephrologist referral, laboratory investigations showed GFR 60 mL/min per 1.73 m2, metabolic acidosis, hypouricemia, hypokalemia, hypophosphatemia, glycosuria, proteinuria, high FEUa and FEK, and low GFR of phosphorus. Fancony syndrome was diagnosed and adequate supplementation was initiated. After literature review the most probable causing agent was ifosfamide. After adequate treatment patient’s general condition improved with slow percentile recovery. Conclusions: Nephrotoxicity secondary to chemotherapy is a major cause of morbidity in pediatric cancer survivors. Our case represents a rare situation with unspecific clinical signs. Clinicians must be alert to the necessity of close monitoring to identify renal toxicity as early as possible and allow adequate supplementation, which is crucial in preventing side effects.info:eu-repo/semantics/publishedVersio

Influenza B-Associated Atypical Hemolytic Uremic Syndrome

Introduction: Influenza A infections have been described to cause secondary hemolytic uremic syndrome and to trigger atypical hemolytic uremic syndrome (aHUS) in individuals with an underlying genetic complement dysregulation. To date, Influenza B has only been reported to trigger aHUS in 2 patients. In 61% of aHUS cases, mutations are found in H, B and I factors, membrane cofactor protein (MCP), C3 and thrombomodulin. MCP (CD46) mutations account for 10-15% of cases. Clinical Case: A 13-year-old boy was transferred to a terciary pediatric centre with acute renal lesion in the context of HUS. Evidence was found for Influenza B infection and results for other etiologic agents were negative. He was treated with Oseltamivir for 5 days. Etiologic study revealed decreased C ́3 (0,81 g/L), normal C ́4 (0,27 g/L) and all antibodies were negative: anti-Beta2 GP1 IgG / IgM, anti-cardiolipine IgG / IgM, anti-neutrophil-citoplasm-PR3 and MPO. Alternate complement pathway study (AH 50) were 112 % of normal value (reference value >70%) and ADAMTS 13 activity were 0.79 (values above 0.67 may be found in aSHU as well as other microangiopathic trombopathies). Molecular study of complement including 11 genes (CFH, CD46 (MCP), CFI, C3, THBD, CFB,CFHR5, CFHR1 CFHR3, CFHR4, DGKE) found a pathogenic heterozygotic missense variant on CD46 (MCP) gene, c.554A>G, p.Asp185Gly, associated with aHUS. Conclusions: aHUS patients should be screened for all known disease-associated genes. Screening should not be stopped after finding a mutation to avoid missing other genetic susceptibility factors influencing disease phenotype, particularly in patients with MCP or CFI mutations, because they have a higher probability of also carrying mutation in another gene than patients with CFHor C3 mutations. Influenza B is a trigger for aHUS and might be underreported as such. Influenza vaccination may protect patients at risk.info:eu-repo/semantics/publishedVersio

Non-AIDS-related comorbidities in people living with HIV-1 aged 50 years and older: The AGING POSITIVE study.

OBJECTIVE: To characterize the profile of non-AIDS-related comorbidities (NARC) in the older HIV-1-infected population and to explore the factors associated with multiple NARC. METHODS: This was a multicentre, cross-sectional study including HIV-1-infected patients aged ≥50 years, who were virologically suppressed and had been on a stable antiretroviral therapy (ART) regimen for at least 6 months. A multiple regression model explored the association between demographic and clinical variables and the number of NARC. RESULTS: Overall, 401 patients were enrolled. The mean age of the patients was 59.3 years and 72.6% were male. The mean duration of HIV-1 infection was 12.0 years and the median exposure to ART was 10.0 years. The mean number of NARC was 2.1, and 34.7% of patients had three or more NARC. Hypercholesterolemia was the most frequent NARC (60.8%), followed by arterial hypertension (39.7%) and chronic depression/anxiety (23.9%). Arterial hypertension and diabetes mellitus were the most frequently treated NARC (95.6% and 92.6% of cases, respectively). The linear regression analysis showed a positive relationship between age and NARC (B=0.032, 95% confidence interval 0.015-0.049; p=0.0003) and between the duration of HIV-1 infection and NARC (B=0.039, 95% confidence interval 0.017-0.059; p=0.0005). CONCLUSIONS: A high prevalence of NARC was found, the most common being metabolic, cardiovascular, and psychological conditions. NARC rates were similar to those reported for the general population, suggesting a larger societal problem beyond HIV infection. A multidisciplinary approach is essential to reduce the burden of complex multi-morbid conditions in the HIV-1-infected population.info:eu-repo/semantics/publishedVersio

Ciliopatias – Experiência de uma Unidade de Nefrologia Pediátrica de um Hospital Terciário

Introdução: As ciliopatias constituem um grupo de doenças associadas a mutações genéticas que condicionam alterações na estrutura e função dos cílios. A disfunção ciliar pode manifestar-se com doença renal, degeneração retiniana e anomalias cerebrais. Outras manifestações menos frequentes são a doença fibroquística congénita do fígado, diabetes, obesidade e displasia óssea. Objetivo: Caracterizar os casos de ciliopatias seguidos na Unidade de Nefrologia Pediátrica de um Hospital Terciário, nos últimos 10 anos. Resultados: No período em estudo (Janeiro de 2008 a Dezembro de 2017) foram seguidos na Unidade de Nefrologia Pediátrica 8 doentes com ciliopatias; 62,5 % do sexo feminino, 7 doentes de nacionalidade portuguesa e 1 natural do Paquistão. No momento do diagnóstico 2 doentes tinham função renal normal e 6 doença renal crónica (DRC): 1 DRC estadio III, 1 DRC estadio IV e 4 (50%) DRC estadio V; destes 4 realizaram diálise peritoneal e 1 hemodiálise, sendo 4 já submetidos a transplante renal. Dois doentes têm estudo genético concluído, ambos com mutação no gene NPHP1, um deles com Síndrome de Senior Loken. Um doente apresenta Síndrome de Alström e 1 doente apresenta Síndrome de Joubert. Foram submetidos a biópsia renal 5 doentes, todos com alterações compatíveis com nefronoptisis. Conclusões: As ciliopatias constituem um grupo heterogéneo de doenças, com atingimento renal variável e com possível progressão para insuficiência renal crónica. Muitos casos apenas são diagnosticados em estadios avançados de doença renal, pela indolência da progressão da patologia. Salienta-se a necessidade de um elevado grau de suspeição, nomeadamente quando existe atingimento multissistémico (ocular, neurológico, esquelético ou endocrinológico). Nos casos com atingimento primordial renal, é muito frequente a anemia grave e a poliúria/polidipsia severas, que poderão também constituir orientações para o diagnóstico. Quando há envolvimento renal ligeiro, torna-se essencial manter a vigilância clínica e laboratorial, pelo potencial de evolução para DRC.info:eu-repo/semantics/publishedVersio

Everolimus no Tratamento da Esclerose Tuberosa

Introdução: A esclerose tuberosa (ET) é um distúrbio genético que atinge vários processos celulares, resultando numa variedade de lesões hamartomatosas que podem afetar qualquer órgão. O envolvimento renal constitui a segunda causa de morte prematura, sendo os angiomiolipomas (AML) a alteração mais frequente (70-80% dos doentes) e cuja sintomatologia está diretamente relacionada com as dimensões dos AML. Descrição do caso: Adolescente de 16 anos, com antecedentes familiares de ET e suspeita pré-natal da doença, cumprindo critérios diagnósticos no período neonatal precoce (rabdomiomas cardíacos, lesões quísticas renais, hamartomas subependimários e displasia cortical temporo-occipital). Evolução progressiva da doença, com envolvimento neurológico (espasmos infantis aos 4 meses, com evolução para epilepsia focal temporal esquerda), oftalmológico (facomas identificados aos 6 meses), renal (HTA desde os 6 meses; aumento do número e dimensões dos quistos/AML e doença renal crónica (DRC) progressiva, atualmente com TFG de 11.5 ml/min/1.73m2) e cutâneo (angiofibromas, placas moluscóides planas e manchas acrómicas). Acompanhado em consulta de Nefrologia Pediátrica em hospital terciário desde há 1.5 anos, tendo sido medicado com everolimus sistémico que cumpre diariamente há 9 meses, com resposta positiva a nível neurológico, cutâneo e renal (redução de cerca de 33% das dimensões dos AML na ressonância magnética de controlo aos 6 meses de terapêutica), embora sem recuperação da função renal, necessitando de técnica dialítica. Discussão: O envolvimento renal pode evoluir para DRC terminal por destruição do parênquima renal, substituído por AML. A terapêutica com everolimus pode retardar a progressão da doença, reduzindo significativamente as dimensões dos AML renais (35-58% dos casos), estabilizando a função renal e reduzindo a probabilidade de desenvolver sintomatologia e/ou complicações, com benefício também para outros órgãos, nomeadamente na redução de convulsões e na melhoria das lesões cutâneas. Os critérios para início do fármaco estão bem definidos e a sua introdução não deve ser adiada. Neste caso, com diagnóstico muito precoce, o fármaco foi iniciado tardiamente, numa fase já quase sem reserva de parênquima renal, o que não permitiu recuperar a sua função, apesar da redução significativa das dimensões dos AML.info:eu-repo/semantics/publishedVersio

Chronic Hepatitis C Treatment in HIV Co-Infection in Portugal: Results from a Cohort OF 2133 Patients Presented by GEPCOI (Portuguese Coinfection Study Group)

Direct-acting antiviral drugs (DAAs) have recently changed the paradigm of hepatitis C therapy, significantly improving treatment response rates, patient life expectancy and quality of life. In Portugal, sofosbuvir (SOF) and SOF/ledipasvir (SOF/LDV) were fully reimbursed by the National Health System since early 2015 and generalized use of interferon-free DAA based regimens became current practice. During 2016, the remaining DAAs were sequentially added and covered by the same health access policy. The Portuguese Study Group of Hepatitis and HIV Co-infection (GEPCOI) collected data from 15 clinical centres in Portugal, pertaining to the HCV treatment experience with DAA regimens. A cohort of 2133 patients was analysed, representing one of the largest DAA treated HCV/HIV co-infected individuals. The global sustained virologic response (SVR) achieved was 95% in this real-life cohort setting. Linear regression analysis showed significant differences in treatment response rates when using SOF plus ribavirin (RBV) combination in genotype 2 or 3 infected individuals (P < .002) and in those with liver cirrhosis (P < .002). These findings corroborate that early treatment is mandatory in HIV/HCV co-infected patients, as response rates may be negatively influenced by higher fibrosis stages and suboptimal DAA regimens. The current national Portuguese health policy should continue to promote wider treatment access and individualized therapy strategies, aiming at the elimination of HCV infection in this high-risk co-infected population.info:eu-repo/semantics/publishedVersio