25 research outputs found
Oxidative Stress in Cystinosis Patients
Background/Aims: Nephropathic cystinosis (NC) is a severe systemic disease and cysteamine improves its prognosis. Lysosomal cystine accumulation is the hallmark of cystinosis and is regarded as the primary defect due to mutations in the CTNS gene. However, there is great evidence that cystine accumulation itself is not responsible for all abnormalities observed in NC. Studies have demonstrated altered ATP metabolism, increased apoptosis, and cell oxidation. An increased number of autophagosomes and autophagic vacuoles have been observed in cystinotic fibroblasts and renal epithelial cells, suggesting that altered autophagy plays a role in NC, leading to increased production of reactive oxygen species. Therefore, cystinosis patients can be more susceptible to oxidative stress (OS) and it can contribute to the progression of the renal disease. Our goal was to evaluate a marker of OS (serum TBARS) in NC children, and to compare the results with those observed in healthy controls and correlated with renal function parameters. Methods: The study included patients aged under 18 years, with good adherence to the treatment and out of renal replacement therapy. The following parameters were evaluated: serum creatinine, BUN, creatinine clearance estimated by stature and serum TBARS levels. Results: We selected 20 patients aged 8.0 ±3.6 years and observed serum TBARS levels of 4.03 ±1.02 nmol/ml. Serum TBARS levels in the 43 healthy controls, aged 7.4 ±1.1 years, were 1.60 ±0.04 nmol/ml. There was a significant difference between the plasma TBARS levels among the 2 groups (p Conclusion: An increased level of serum TBARS in patients with NC was observed and this abnormality was not correlated with the renal function status degree. This is the first report that shows increased oxidative stress in serum of NC patients
Dental abnormalities and oral health in patients with Hypophosphatemic rickets
INTRODUCTION: Hypophosphatemic rickets represents a group of heritable renal disorders of phosphate characterized by hypophosphatemia, normal or low serum 1,25 (OH)2 vitamin D and calcium levels. Hypophosphatemia is associated to interglobular dentine and an enlarged pulp chambers. AIM: Our goal was to verify the dental abnormalities and the oral health condition in these patients. MATERIAL AND METHODS: Prospective study of oral conditions in patients with Hypophosphatemic rickets. This report employed a simple method to be easily reproducible: oral clinical exam and radiographic evaluation. RESULTS: Fourteen patients were studied, 5 males, median age of 11years (4 to 26). Occlusion defects (85,7%) and enamel hypoplasia (57,1%) were significant more frequently than dental abscesses (one patient). We observed enlarged pulp chambers in 43% of the patients and hypoplasia and dentin abnormalities in 14,3%. We could not detect a significant correlation between dental abnormalities and delayed treatment (p>0,05). DMFT index for 6 to 12 years patients (n = 12) showed that the oral health is unsatisfactory (mean DMFT = 5). CONCLUSIONS: Patients with Hypophosphatemic Rickets frequently present dental alterations and these are not completely recovered with the treatment, unless dental abscess and they need a periodical oral examination
Pharmacokinetics of cyclosporin - a microemulsion in children with idiopathic nephrotic syndrome
OBJECTIVE: We present a prospective study of a microemulsion of cyclosporin to treat idiopathic nephrotic syndrome in ten children with normal renal function who presented cyclosporin trough levels between 50 and 150 ng/ml and achieved complete remission with cyclosporin. To compare the pharmacokinetic parameters of cyclosporin in idiopathic nephrotic syndrome during remission and relapse of the nephrotic state. METHOD: The pharmacokinetic profile of cyclosporin was evaluated with the 12-hour area under the time-concentration curve (auc0-12) using seven time-point samples. This procedure was performed on each patient during remission and relapse with the same cyclosporin dose in mg/kg/day. The 12-hour area under the time-concentration curve was calculated using the trapezoidal rule. All of the pharmacokinetic parameters and the resumed 4-hour area under the time-concentration curve were correlated with the 12-hour area under the time-concentration curve. ClinicalTrials.gov: NCT01616446. RESULTS: There were no significant differences in any parameters of the pharmacokinetic of cyclosporin during remission and relapse, even when the data were normalized by dose. The best correlation with the 12-hour area under the time-concentration curve was the 4-hour area under the time-concentration curve on remission and relapse of the disease, followed by the 2-hour level after cyclosporin (c2) dosing in both disease states. CONCLUSIONS: These data indicate that the same parameters used for cyclosporin therapeutic monitoring estimated during the nephrotic state can also be used during remission. Larger controlled studies are needed to confirm these findings.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2012/12285-7]Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP
Doenças raras: o que o pediatra necessita saber
Rare disease or an orphan disease is a disease that affects a small percentage of the population. Most of these diseases are present throughout the patients life, even if the symptoms do not appear immediately. They are often fatal or chronically debilitating and the impact on the quality of life of patients and their families is significant. Patients with rare diseases often experience delays in diagnosis, which can negatively impact management and delay treatment. Familial genetic testing or cascade genotyping of all newly diagnosed individuals can speed up the diagnosis of these diseases and allow more patients to be identified at a younger age. Care for patients with chronic and rare diseases is complex, mainly due to lack of knowledge about the disease, which makes accurate and early diagnosis difficult, in addition to the need to perform specific tests, which are sometimes highly complex and costly. Added to these factors are difficulties in obtaining adequate treatment when available, raising awareness of the patient and family about the disease and adherence to treatment.A multidisciplinary approach is very important: care provided by a doctor, nurse, psychologist, nutritionist and social worker. These professionals, in addition to medical care, address the particularities of the disease and treatment, the impact on the life of the patient and his family, the approach to psychological and social issues, and guidance regarding medications and diets
Nephrogenic Diabetes Insipidus (NDI): Clinical, Laboratory and Genetic Characterization of Five Brazilian Patients
INTRODUCTION: Nephrogenic diabetes insipidus is characterized by a lack of response in the distal nephron to the antidiuretic hormone arginine vasopressin. Manifestations include polyuria, polydipsia, hyposthenuria, recurrent episodes of dehydration and fever and growth failure. Most cases are caused by mutations in the AVPR2 gene. The mutant receptors are trapped intracellularly. METHOD: We studied five boys using clinical, laboratory and molecular data. The mean age at diagnosis was 14.6 months (range 6 to 24) and 12.2 years (7.8 to 19) after the follow-up period. The mean period of follow-up was 132.2 ± 50.9 months. RESULTS: The geometric means of the z-scores of weight and stature were -4.5 and -3.6, respectively, at diagnosis. At the last medical appointment, the z-scores of weight and stature were -0.3 and -0.9, respectively. Three patients were diagnosed with ureterohydronephrosis and exhibited increased post-void urine volume. Mutations in the AVPR2 gene were found in all patients, and the carrier status was confirmed in four of five cases. Two unrelated children presented identical mutations (S167L) in arginine vasopressin R2. Two of the patients had a mutation that has already been described in other Brazilian families (R337X), and one patient showed a de novo mutation (Y128D) in arginine vasopressin R2, since his mother's molecular analysis was normal. The recurrence risk for this family was significantly reduced. CONCLUSION: This study reports the clinical and laboratory characterization of Nephrogenic diabetes insipidus and reiterates the importance of the genetic basis that underlies the disease diagnosis and genetic counseling
Clinical and diagnostic aspects of Fabry disease management : a narrative review with a particular focus on Brazilian experts’ perspectives
Research on the genetics, epidemiology, and clinical manifestations of Fabry disease (FD) has increased significantly in recent years. However, some relevant clinical questions still need to be answered to develop better approaches to patient management. This review focuses on answering specific questions raised by Brazilian experts based on their experience in diagnosing and managing patients with FD. The questions are as follows: What is the role of globotriaosylsphingosine in diagnosis? How does one proceed with the diagnosis if there is a variant of unknown significance? What are the earliest and most reliable markers of renal, cardiac, and neurological impairment? What is the prevalence of FD in patients with cryptogenic stroke? What is the average delay in diagnosis in patients with FD? Based on these questions, our objective was to highlight epidemiological, diagnostic, and clinical aspects relating to the literature in the FD field
The long-term use of enalapril and hydrochlorothiazide in two novel mutations patients with Dent's disease type 1
A doença de Dent é uma tubulopatia ligada ao X causada por mutações no gene que codifica o canal de cloro CLCN-5 e é caracterizada por proteinúria de baixo peso molecular, hipercalciúria, nefrocalcinose e insuficiência renal. Vários casos têm sido descritos, nos quais o único sintoma na apresentação foi proteinúria assintomática e glomerulosclerose global ou segmentar. A insuficiência renal nesses pacientes pode ser causada pela hipercalciúria e proteinúria persistente. Portanto, o inibidor da enzima de conversão da angiotensina e os tiazÃdicos poderiam ser úteis. O objetivo desta pesquisa é relatar os efeitos destas drogas em dois pacientes com doença de Dent tipo 1 com mutações novas. Neste relato não foram observadas correlações significativas entre dose de hidroclorotiazida e calciúria e entre enalapril e proteinúria. Este achado é importante, pois, sendo pacientes poliúricos, o uso destas drogas poderia prejudicar a função rena
Eculizumab for the treatment of atypical hemolytic uremic syndrome: case report and revision of the literature
SHU atypical (aHUS), that is, not associated with Escherichia coli Shiga toxinproducing, is seen in 5 to 10% of cases of Hemolytic Uremic Syndrome (HUS), and can occur at any age and may be sporadic or familial. The prognosis in these cases is reserved, with high mortality and morbidity in the acute phase of the disease, and about 50% of cases can develop chronic kidney disease. The increased knowledge of the pathogenesis of aHUS (overactivation of the alternative pathway of complement), was accompanied by the appearance of a drug, eculizumab, which acts as an inhibitor of membrane attack complex. Our goal is to report a case of infant with aHUS with excellent clinical and laboratory response with the use of eculizumab. 14 month old infant, previously healthy, male, presented anemia and thrombocytopenia at 12 months of age. He was treated with corticosteroids and forwarded to our service for high blood pressure. However, the scans showed nephrotic proteinuria with renal involvement and hypoalbuminemia with direct Coombs negative. He developed anemia, thrombocytopenia, worsening of renal function and hypertension. Renal biopsy showed thrombotic microangiopathy (TMA). On the non-hemolytic anemia, thrombocytopenia and acute renal failure with histological substrate MAT, was diagnosed of aHUS. The patient received eculizumab excellent clinical and laboratory response. This case shows the importance of early diagnosis and treatment of the aHUS. Eculizumab is effective and keeps long-term remission, avoiding invasive measures such as plasmapheresis, which resolves only part of the picture.SÃndrome HemolÃtico Urêmica atÃpica (SHUa), isto é, não associada à Escherichia coli, produtora de Shiga toxina, é vista em 5% a 10% dos casos de SÃndrome HemolÃtico Urêmica (SHU), podendo ocorrer em qualquer idade e ser esporádica ou familiar. O prognóstico nestes casos é reservado, com alta mortalidade e morbidade na fase aguda da doença, e cerca de 50% dos casos podem evoluir para doença renal crônica terminal. O aumento do conhecimento da patôgenese da SHUa (hiperativação da via alternativa do complemento) foi acompanhado pelo surgimento de uma droga, eculizumab, a qual age como inibidor da via final do complemento. Nosso objetivo é relatar um caso de lactente com SHUa que apresentou excelente resposta clÃnica e laboratorial com o uso de eculizumab. Lactente, 14 meses de idade, sexo masculino, previamente hÃgido, apresentou quadro de anemia e plaquetopenia aos 12 meses de idade. Foi tratado com corticoterapia e encaminhado ao nosso serviço por hipertensão arterial. Entretanto, os exames demonstraram acometimento renal com proteinúria nefrótica e hipoalbuminemia, com Coombs direto negativo. Evoluiu com anemia, plaquetopenia, piora de função renal e hipertensão. Realizada biópsia renal que mostrou microangiopatia trombótica (MAT). Diante do quadro de anemia não hemolÃtica, plaquetopenia e insuficiência renal aguda com substrato histológico de MAT, foi feito diagnóstico de SHUa. O paciente recebeu eculizumab, com excelente resposta clÃnico-laboratorial. Este caso denota a importância de diagnóstico e tratamento precoces nesta entidade grave que é a SHUa. Eculizumab é eficaz e mantém remissão a longo prazo, evitando medidas invasivas como a plasmaferese, a qual resolve apenas parcialmente o quadro.23724
Determinação dos nÃveis urinários da proteÃna transportadora do retinol (RBP) em recém-nascidos pré-termo, lactantes e crianças maiores
BV UNIFESP: Teses e dissertaçõe