Neurologic involvement in atypical hemolytic uremic syndrome and successful treatment with eculizumab

WOS: 000316571400019PubMed ID: 23389237Atypical hemolytic uremic syndrome (aHUS) is associated with defective regulation of the complement pathway. Neurological involvement is the most common extrarenal complication and represents a major cause of mortality and morbidity. Two girls aged 11 and 6 years, respectively, developed aHUS and were treated immediately with plasma exchange (PE) and fresh frozen plasma infusion (PI). Although initial improvement in renal function was seen in both cases, the first patient showed progressing thrombotic microangiopathy (TMA) despite daily PE, and neurological manifestations (seizures, vision loss, loss of balance, and confusion) developed after 1 month. The second patient developed cerebral TMA (seizures, vision loss, and nystagmus) 6 days after initial presentation and remained unresponsive to PE/PI. Neurological symptoms were similar in both patients, even though they had different complement protein mutations. Treatment with eculizumab achieved complete control of neurological symptoms within 24 h and gradually normalized hematological and renal parameters in both children. Based on our two cases, we conclude that eculizumab is a rapid-acting, effective, and life-saving treatment for pediatric patients with aHUS and severe neurological involvement, which works by inhibiting complement-mediated TMA in the kidney and other organs, such as the brain.Alexion PharmaceuticalsAssistance with writing this manuscript was provided by Bioscript Stirling Ltd, UK, and funded by Alexion Pharmaceuticals. We give special thanks to Dr. Reyhan Diz Kucukkaya in the Department of Internal Medicine, Division of Hematology at Istanbul Bilim University, Istanbul, Turkey

TURKISH ATYPICAL HEMOLYTIC UREMIC SYNDROME REGISTRY: ECULIZUMAB TREATMENT IN AHUS PATIENTS

WOS: 000443998400089

Neonatal cerebral sinovenous thrombosis: Two cases, two different gene polymorphisms and risk factors

Cerebral sinovenous thrombosis (CSVT) is a rare disease in the neonatal period and also the greatest risk of neonatal mortality and morbidity. In this report, we presented two cases with CSVT and different risk factors. One of these cases had methylenetetrahydrofolate reductase (MTHFR) C677T homozygous polymorphism and the other case had both MTHFR A1298C homozygous polymorphism, plasminogen activator inhibitor-1 (PAI-1) 4G/5G polymorphism and elevated lipoprotein a. Early diagnosis and prompt initiation of therapy of neonatal CSVT may prevent neonatal mortality and poor long-term neurodevelopmental outcomes

Eculizumab treatment and discontinuation in pediatric patients with atypical hemolytic uremic syndrome: a multicentric retrospective study

Introduction Eculizumab is effective treatment of pediatric atypical hemolytic uremic syndrome (aHUS). However, the optimal duration of treatment is not clearly defined. The aim of this study was to retrospectively analyze the outcome of pediatric patients with aHUS, who started eculizumab treatment but discontinued it during the follow-up period

Basal damage and oxidative DNA damage in children with chronic kidney disease measured by use of the comet assay

One consequence of chronic kidney disease (CKD) is an elevated risk for cancer. There is sufficient evidence to conclude that there is an increased incidence of at least some cancers in kidney-dialysis patients. Cancer risk after kidney transplantation has mainly been attributed to immunosuppressive therapy. There are no data evaluating DNA damage in children with CKD, in dialysis patients, or following kidney transplantation. In this study, the comet assay and the enzyme-modified comet assay - with the use of endonuclease III (Endo III) and formamidopyrimidine glycosylase (FPG) enzymes - were conducted to investigate the basal damage and the oxidative DNA damage as a result of treatment in peripheral blood lymphocytes of children. Children at various stages of treatment for kidney disease, including pre-dialysis patients (PreD) (n = 17), regular hemodialysis patients (HD) (n = 15), and those that received kidney transplants (Tx) (n = 17), comprised the study group. They were compared with age- and gender-matched healthy children (n = 20) as a control group. Our results show that the %DNA intensity, a measure of basal damage, was significantly increased in children with CKD (mean +/- SD) (5.22 +/- 1.57) and also in each of the PreD, HD, and Tx groups [(4.92 +/- 1.23), (4.91 +/- 1.35), and (5.79 +/- 1.94), respectively, vs the healthy children (2.74 +/- 2.91) (p < 0.001). Significant increases in oxidative DNA damage were only found in the FPG-sensitive sites for the PreD and Tx groups, compared with control and HD groups (p < 0.05), suggesting that basal DNA damage was more evident for the PreD, HD, and Tx groups. The findings of the present study indicate a critical need for further research on genomic damage with different endpoints and also for preventive measures and improvements in treatment of pediatric patients, in order to improve their life expectancy. (C) 2011 Elsevier B.V. All rights reserved

Hemolytic uremic syndrome outbreak in Turkey in 2011

The aim of this retrospective multicenter study was to define the epidemiological and clinical features and prognostic factors of the first diarrhea-related hemolytic uremic syndrome (D+HUS) outbreak in Turkey in 2011