Ravulizumab in Atypical Hemolytic Uremic Syndrome: An Analysis of 2-Year Efficacy and Safety Outcomes in 2 Phase 3 Trials.

Rationale & Objective: Atypical hemolytic uremic syndrome (aHUS) is a rare form of thrombotic microangiopathy (TMA) caused by complement dysregulation. Ravulizumab is a C5i approved for the treatment of aHUS. This analysis assessed long-term outcomes of ravulizumab in adults and pediatric patients with aHUS. Study Design: This analysis reports 2-year data from 2 phase 3, single-arm studies. Setting & Participants: One study included C5i-naïve adults (NCT02949128), and the other included 2 cohorts of pediatric patients (C5i-naïve and those who switched to ravulizumab from eculizumab [pediatric switch patients]; NCT03131219). Exposure: Patients received intravenous ravulizumab every 4-8 weeks, with the dose depending on body weight. Outcomes: The primary endpoint in the studies of C5i-naïve patients was complete TMA response, which consisted of platelet count normalization, lactate dehydrogenase normalization, and ≥25% improvement in serum creatinine concentrations from baseline, at 2 consecutive assessments ≥4 weeks apart. Analytical Approach: All analyses used descriptive statistics. No formal statistical comparisons were performed. Results: In total, 86 and 92 patients were included in efficacy and safety analyses, respectively. Complete TMA response rates over 2 years were 61% and 90% in C5i-naïve adults and pediatric patients, respectively. The median increase in estimated glomerular filtration rate from baseline was maintained over 2 years in C5i-naïve adults (35 mL/min/1.73 m2) and pediatric patients (82.5 mL/min/1.73 m2). Most adverse events and serious adverse events occurred during the first 26 weeks. No meningococcal infections were reported. Improvement in the Functional Assessment of Chronic Illness Therapy - Fatigue score achieved by 26 weeks was maintained over 2 years. Limitations: Limitations were the small sample of pediatric switch patients and limited availability of genetic data. Conclusions: Long-term treatment with ravulizumab is well tolerated and associated with improved hematologic and renal parameters and quality of life in adults and pediatric patients with aHUS.

This research tested a drug called ravulizumab for the treatment of atypical hemolytic uremic syndrome (aHUS). aHUS is a rare disease that causes clots in tiny blood vessels. This can damage the kidneys and other organs. We analyzed data from 2 clinical trials in which children and adults with aHUS received ravulizumab through a tube placed in a vein (intravenous line). They received ravulizumab every 4-8 weeks depending on their weight. We found that treating patients for 2 years with ravulizumab was associated with improved blood health, kidney function, and quality of life and was well tolerated. These results support ravulizumab as a long-term treatment for people with aHUS.

Atypical hemolytic-uremic syndrome after COVID-19 vaccine: A case report.

BACKGROUND: The emergence of new SARS-CoV-2 variants and the global COVID-19 pandemic spurred urgent vaccine development. While common vaccine side effects are well-documented, rare adverse events necessitate post-marketing surveillance. Recent research linked messenger RNA vaccines to thrombotic microangiopathy (TMA), a group of syndromes characterized by microvascular hemolytic anemia and thrombocytopenia. This report describes a new-onset atypical hemolytic-uremic syndrome (aHUS) occurring after COVID-19 vaccination and complements recent literature. CASE PRESENTATION: A previously healthy 25-year-old woman developed malaise, nausea, edema, and renal dysfunction 60 days postvaccination. Laboratory findings confirmed TMA diagnosis. Genetic testing for complement system mutations was negative. Kidney biopsy supported the diagnosis, and the patient required hemodialysis. CONCLUSION: This case illustrates the rare occurrence of aHUS following COVID-19 vaccination, with unique characteristics compared to previous reports. Despite the critical role of vaccination in pandemic control, emerging adverse events, such as vaccine-related TMA, must be recognized and investigated. Additional clinical trials are imperative to comprehend the clinical features and pathophysiological mechanisms underlying TMA associated with COVID-19 vaccination.

Clinical presentation and management of atypical hemolytic uremic syndrome in Latin America: a narrative review of the literature.

INTRODUCTION: Comprehensive information about atypical hemolytic uremic syndrome (aHUS) is relatively scarce outside of Europe and North America. This narrative review assembles available published data about the clinical presentation and management of aHUS in Latin America. AREAS COVERED: A search conducted in February 2023 of the MEDLINE (from inception), Embase (from inception), and LILACS/IBECS (1950 to 2023) databases using search terms 'atypical hemolytic uremic syndrome' and 'Latin America' and their variations retrieved 51 records (full papers and conference abstracts) published in English, Spanish, or Portuguese. After de-duplication, manual screening of titles/abstracts and addition of author-known articles, 25 articles were included of which 17 (68%) are full papers. All articles were published during the years 2013-2022. Articles include cohort studies, a registry analysis, and case reports from Argentina, Brazil, Chile and Columbia. Overall, Latin American patients with aHUS present the classic epidemiological, clinical, and genetic characteristics associated with this condition as described in other world regions. Depending on the country and time of reporting, aHUS in Latin America was treated mainly with plasma therapy and/or eculizumab. Where reported, eculizumab substantially improved aHUS-related outcomes in almost all adult and pediatric patients. EXPERT OPINION: Eculizumab has dramatically altered the natural course of aHUS, improving prognosis and patient outcomes. Addressing economic challenges and investing in healthcare infrastructure will be essential to implement strategies for timely detection and early treatment of aHUS in Latin America.

Pregnancy-associated atypical hemolytic uremic syndrome. Case report.

Pregnancy-associated atypical hemolytic uremic syndrome (P-aHUS) is a rare disease. There are only few reports in the literature, and most are in the puerperium period. It is a thrombotic microangiopathy (TMA) characterized for microangiopathic hemolytic anemia, thrombocytopenia, and renal dysfunction. We report the case of a pregnant patient at 26.3 gestation weeks, who developed clinical features of TMA, neurological alterations, and septic shock; then after fetus and placental delivery, no clinical improvement was observed; a diagnostic protocol was performed due to suspicion of P-aHUS, showing improvement after the plasma exchange sessions and eculizumab. We present here a brief review of the case since it is an entity that needs to be suspected during pregnancy when TMA features and requires an immediate diagnosis to provide timely treatment.

Atypical Hemolytic Uremic Syndrome: A Nationwide Colombian Pediatric Series.

Objectives. Atypical hemolytic uremic syndrome (aHUS) is a rare complement-mediated kidney disease with genetic predisposition and represents up to 10% of pediatric hemolytic uremic syndrome (HUS) cases. Few studies have evaluated aHUS in Latin American population. We studied a Colombian pediatric cohort to delineate disease presentation and outcomes. Methods. A multicenter cohort of 27 Colombian children with aHUS were included. Patients were grouped by age at onset. Clinical features were compared using analysis of variance (ANOVA) and Fisher exact tests. Renal biopsy was performed on 6 patients who were suspected of having other renal diseases before aHUS diagnosis. Results. Most patients were male (70%). The onset of aHUS occurred frequently before age 4 years (60%) and followed gastroenteritis as the main triggering event (52%). Age groups showed comparable clinical presentation, disease severity, treatment, and outcomes. Pulmonary involvement (67%) was the main extrarenal manifestation, particularly in the 1 to 7 age group (P = .01). Renal biopsies were as follows: 3 had membranoproliferative glomerulonephritis (MPGN) type I, one MPGN type III, one C3-glomerulonephritis, and one rapidly progressive GN. Genetic screening was available in 6 patients and identified 2xCFHR5, 2xMCP, 1xADAMTS13/THBD, and 1xDGKE mutations. A total of 15 relapses were seen, of which 8 (72%) occurred in the 1 to 7 age group. The renal outcome was not significantly different regardless of age group. Conclusion. In our cohort, we observed a relatively high frequency of extrarenal involvement at first presentation represented by pulmonary manifestations. The renal prognosis at initial presentation was worse than in previous reports.

Síndrome hemolítico urémico secundario a Streptococcus pneumoniae. Reporte de un caso clínico / Streptococcus pneumoniae associated hemolytic uremic syndrome. Case report

El síndrome hemolítico urémico secundario a Streptococcus pneumoniae (SHU-Sp) es una complicación poco frecuente de las enfermedades invasoras por S. pneumoniae. Presenta una alta morbimortalidad, con requerimiento de transfusiones de glóbulos rojos y plaquetas, terapia de sustitución de la función renal de inicio precoz y más prolongada, así como mayores complicaciones a largo plazo, comparado con las formas secundarias a infección entérica por Escherichia coli productora de toxina Shiga. Presentamos el caso clínico de una preescolar de dos años, previamente sana, vacunada con tres dosis de PCV13, que desarrolló una insuficiencia renal aguda, anemia hemolítica y plaquetopenia, en el contexto de una neumonía con empiema y bacteriemia por S. pneumoniae.

Streptococcus pneumoniae associated hemolytic uremic syndrome (Sp-HUS) is an uncommon complication of invasive pneumococcal infections. Patients with Sp-HUS have a higher mortality and long term morbidity than those due to HUS from Shiga toxin-producing Escherichia coli infections (STEC-HUS). They often require more red blood cells and platelet transfusions, and early initiation of renal substitution therapy, presenting a higher rate of arterial hypertension and chronic renal disease in the long term, compared to STEC-HUS. We report a healthy 2 year-old infant, vaccinated with three doses PCV13, that developed acute renal failure, hemolytic anemia and thrombocytopenia in the course of a complicated pneumococcal pneumonia with empyema and bacteremia.

A comprehensive model for assessing and classifying patients with thrombotic microangiopathy: the TMA-INSIGHT score.

BACKGROUND: Thrombotic Microangiopathy (TMA) is a syndrome characterized by the presence of anemia, thrombocytopenia and organ damage and has multiple etiologies. The primary aim is to develop an algorithm to classify TMA (TMA-INSIGHT score). METHODS: This was a single-center retrospective cohort study including hospitalized patients with TMA at a single center. We included all consecutive patients diagnosed with TMA between 2012 and 2021. TMA was defined based on the presence of anemia (hemoglobin level < 10 g/dL) and thrombocytopenia (platelet count < 150,000/µL), signs of hemolysis, and organ damage. We classified patients in eight categories: infections; Malignant Hypertension; Transplant; Malignancy; Pregnancy; Thrombotic Thrombocytopenic Purpura (TTP); Shiga toxin-mediated hemolytic uremic syndrome (STEC-SHU) and Complement Mediated TMA (aHUS). We fitted a model to classify patients using clinical characteristics, biochemical exams, and mean arterial pressure at presentation. RESULTS: We retrospectively retrieved TMA phenotypes using automatic strategies in electronic health records in almost 10 years (n = 2407). Secondary TMA was found in 97.5% of the patients. Primary TMA was found in 2.47% of the patients (TTP and aHUS). The best model was LightGBM with accuracy of 0.979, and multiclass ROC-AUC of 0.966. The predictions had higher accuracy in most TMA classes, although the confidence was lower in aHUS and STEC-HUS cases. CONCLUSION: Secondary conditions were the most common etiologies of TMA. We retrieved comorbidities, associated conditions, and mean arterial pressure to fit a model to predict TMA and define TMA phenotypic characteristics. This is the first multiclass model to predict TMA including primary and secondary conditions.

Características del síndrome urémico hemolítico en pacientes de un hospital pediátrico de Perú, 2010-2020 / Characteristics of hemolytic uremic syndrome in patients from a pediatric hospital in Peru, 2010-2020

RESUMEN El propósito del presente estudio fue describir las características clínicas, epidemiológicas, laboratoriales, tratamiento y seguimiento de pacientes con síndrome urémico hemolítico (SUH). Se revisaron las historias clínicas de los pacientes con SUH hospitalizados en el Instituto Nacional de Salud del Niño-Breña (INSN-B) de Lima, Perú. Se incluyeron a 83 pacientes. La mediana de edad fue de 22 meses. El 71,1% (n=59) registró uso previo de antibióticos. El 86,8% (n=72) tuvieron oligoanuria y el 74,6% (n=62) diarrea. Cinco cultivos fueron positivos (dos Escherichia coli enterohemorrágica). Cuarenta y nueve (59%) requirieron terapia de reemplazo renal. Ningún paciente falleció durante la hospitalización. Al año del seguimiento, siete pacientes presentaron nefropatía pos-SUH. En conclusión, en el INSN-B, la mediana de edad fue similar que años anteriores y hubo una mayor frecuencia de oligoanuria y terapia de reemplazo renal en comparación con reportes previos.

ABSTRACT This study aimed to describe the clinical-epidemiological, laboratory, treatment, and follow-up characteristics of patients with hemolytic uremic syndrome (HUS). The medical records of patients with HUS hospitalized at the Instituto Nacional de Salud del Niño-Breña (INSN-B) (Lima, Peru) were reviewed. We evaluated 83 patients. The median age was 22 months (interquartile range: 14 to 30 months). Of the sample, 71.1% (59) registered previous use of antibiotics. Seventy-two (86.8%) had oligoanuria and 62 (74.6%) had diarrhea. Five cultures were positive (two enterohaemorrhagic Escherichia coli). Forty-nine (59%) required renal replacement therapy. No patient died during hospitalization. At one year of follow-up, seven patients developed post-HUS nephropathy. In conclusion, in INSN-B, the median age was like previous years and there was a higher frequency of oligoanuria, and renal replacement therapy compared to previous reports.

The challenges of the pandemic and the vaccination against covid-19 in pediatric patients with kidney disease / Os desafios da pandemia e a vacinação covid-19 na população pediátrica com doenças renais

ABSTRACT The covid-19 vaccine confers direct protection and reduces transmission rates of the virus and new variants. Vaccines from Pfizer/BioNTech and CoronaVac have been cleared for children in Brazil. They are safe, effective, and immunogenic. There are no known complications associated with the use of steroids or vaccines in pediatric patients with covid-19 and nephrotic syndrome. With or without immunosuppression, these patients are not at increased risk of severe covid-19, and steroids are safe for them. A milder form of covid-19 occurs in patients with chronic kidney disease without the need for hospitalization. The vaccine response may be reduced and/or the duration of antibodies after vaccination may be shorter than in the general population. However, considering risk of exposure, vaccination against covid-19 is recommended. It is believed that patients with hemolytic-uremic syndrome are at higher risk of severe covid-19. Vaccination is recommended, although specific data on the safety and efficacy of the covid-19 vaccine are limited. There is agreement that the benefits of induced immunity outweigh the risks of immunization. Vaccination against covid-19 is recommended for children and adolescents needing kidney transplantation or who have undergone transplantation. These patients present decreased immune response after vaccination, but immunization is recommended because the benefits outweigh the risks of vaccination. Current recommendations in Brazil stipulate the use of the messenger RNA vaccine. This paper aims to provide pediatric nephrologists with the latest knowledge about vaccination against covid-19 for children with kidney disease.

Resumo A vacina covid-19 confere proteção direta, reduz as taxas de transmissão do vírus e de novas variantes. No Brasil, estão liberadas para a população pediátrica as vacinas Pfizer/BioNTech e a CoronaVac, ambas seguras, eficazes e imunogênicas. Pacientes pediátricos com síndrome nefrótica e covid-19 têm curso clínico regular sem complicações relacionadas ao uso de esteroides ou vacinas. Esses pacientes, com ou sem imunossupressão, não apresentam maior risco de covid-19 grave e o tratamento com esteroides é seguro. Os pacientes com doença renal crônica têm covid-19 mais leve, sem necessidade de hospitalização. A resposta vacinal pode ser reduzida e/ou a duração dos anticorpos pós-vacinação pode ser menor do que na população geral. Entretanto, a vacina covid-19 está recomendada, considerando o risco de exposição. Acredita-se que pacientes com síndrome hemolítico-urêmica teriam maior risco de covid-19 grave. A vacina é recomendada, embora dados específicos sobre segurança e eficácia da vacina covid-19 sejam limitados. Há concordância que os benefícios da imunidade induzida superam quaisquer riscos da imunização. A vacina covid-19 é recomendada para crianças e adolescentes candidatos ao transplante renal ou já transplantados. Esses pacientes têm resposta imunológica reduzida após a vacina, entretanto ela é recomendada porque os benefícios superam qualquer risco dessa vacinação. A recomendação atual no Brasil é a vacina de tecnologia RNA mensageiro. O objetivo deste documento é levar aos nefrologistas pediátricos os conhecimentos mais recentes sobre a vacinação contra contra-19 em crianças com doenças renais.

Frecuencia de hospitalizaciones por síndrome urémico hemolítico en niños de 0 a 14 años en el Perú, periodo 2015 a 2022

Introducción. Existen limitados reportes epidemiológicos del síndrome urémico hemolítico (SUH) en Latinoamérica. Objetivo. Describir la frecuencia y características de las hospitalizaciones por SUH en niños de 0 a 14 años. Métodos. Se realizó un estudio descriptivo de análisis secundario con datos de hospitalizaciones por SUH de instituciones de salud de Perú en el periodo 2015-2022. Resultados. Se registraron 228 hospitalizaciones. El 52,2% fueron varones. El 88,6% fue menor de cinco años y el 11% menor de un año. Los departamentos con más hospitalizaciones fueron Lima y Arequipa con 133 y 46 casos. Las instituciones del Ministerio de Salud (MINSA) y del Seguro Social (EsSalud) reportaron el 42,5% y 27,6% de las hospitalizaciones. Del 2015 al 2022, la incidencia varió de 0,42 a 1,13 casos/100 000 niños menores de cinco años. Conclusiones. Las hospitalizaciones por SUH fueron más frecuentes en menores de cinco años y en las instituciones del MINSA.

Introduction. There are limited epidemiological reports of hemolytic uremic syndrome (HUS) in Latin America. Objective. To describe the frequency and characteristics of hospitalizations due to HUS in children aged 0 to 14 years. Methods. Descriptive study of secondary analysis was performed with data on hospitalizations due to HUS from healthcare institutions from Peru, 2015-2022. Results. Two hundred twenty-eight hospitalizations were registered, 52.2% were male, 88.6% were under five years old, and 11% were under one year old. The departments with more hospitalizations were Lima (133 cases) and Arequipa (46 cases). The institutions of the Ministry of Health (MINSA) and Social Security (EsSalud) reported 42.5% and 27.6% of hospitalizations. From 2015 to 2022, the incidence ranged from 0.42 to 1.13 cases/100,000 children under five years of age. Conclusions. Hospitalizations due to HUS were more frequent in children under five years of age and MINSA institutions.

Detection and analysis of Shiga toxin producing and enteropathogenic Escherichia coli in cattle from Tierra del Fuego, Argentina.

Shiga toxin producing Escherichia coli (STEC) and enteropathogenic E. coli (EPEC) are pathovars that affect mainly infants' health. Cattle are the main reservoir of STEC. Uremic hemolytic syndrome and diarrheas can be found at high rates in Tierra del Fuego (TDF). This study aimed to establish the prevalence of STEC and EPEC in cattle at slaughterhouses in TDF and to analyze the isolated strains. Out of 194 samples from two slaughterhouses, STEC prevalence was 15%, and EPEC prevalence was 5%. Twenty-seven STEC strains and one EPEC were isolated. The most prevalent STEC serotypes were O185:H19 (7), O185:H7 (6), and O178:H19 (5). There were no STEC eae + strains (AE-STEC) or serogroup O157 detected in this study. The prevalent genotype was stx2c (10/27) followed by stx1a/stx2hb (4/27). Fourteen percent of the strains presented at least one stx non-typeable subtype (4/27). Shiga toxin production was detected in 25/27 STEC strains. The prevalent module for the Locus of Adhesion and Autoaggregation (LAA) island was module III (7/27). EPEC strain was categorized as atypical and with the ability to cause A/E lesion. The ehxA gene was present in 16/28 strains, 12 of which were capable of producing hemolysis. No hybrid strains were detected in this work. Antimicrobial susceptibility tests showed that all strains were resistant to ampicillin and 20/28 were resistant to aminoglycosides. No statistical differences could be seen in the detection of STEC or EPEC either by slaughterhouse location or by production system (extensive grass or feedlot). The rate of STEC detection was lower than the one reported for the rest of Argentina. STEC/EPEC relation was 3 to 1. This is the first study on cattle from TDF as reservoir for strains that are potentially pathogenic to humans.

Hemolytic-uremic syndrome: 24 years' experience of a pediatric nephrology unit / Síndrome hemolítico-urêmica: 24 anos de experiência de uma unidade de nefrologia pediátrica

Abstract Introduction: A better understanding of hemolytic-uremic syndrome (HUS) pathophysiology significantly changed its treatment and prognosis. The aim of this study is to characterize the clinical features, severity, management, and outcomes of HUS patients. Materials and Methods: Retrospective study of HUS patients admitted to a Pediatric Nephrology Unit between 1996 and 2020. Demographic and clinical data regarding etiology, severity, treatment strategies, and patient outcome were collected. Results: Twenty-nine patients with HUS were admitted to our unit, but four were excluded. Median age at diagnosis was two years (2 months - 17 years). Clinical manifestations included diarrhea, vomiting, oliguria, hypertension, and fever. During the acute phase, 14 patients (56%) required renal replacement therapy. Infectious etiology was identified in seven patients (five Escherichia coli and two Streptococcus pneumoniae). Since 2015, 2/7 patients were diagnosed with complement pathway dysregulation HUS and there were no cases of infectious etiology detected. Six of these patients received eculizumab. The global median follow-up was 6.5 years [3 months-19.8 years]. One patient died, seven had chronic kidney disease, four of whom underwent kidney transplantation, one relapsed, and seven had no sequelae. Conclusion: These results reflect the lack of infectious outbreaks in Portugal and the improvement on etiological identification since genetic testing was introduced. The majority of patients developed sequels and mortality was similar to that of other countries. HUS patients should be managed in centers with intensive care and pediatric nephrology with capacity for diagnosis, etiological investigation, and adequate treatment. Long-term follow-up is essential.

Resumo Introdução: Um melhor entendimento da fisiopatologia da síndrome hemolítico-urêmica (SHU) mudou significativamente seu tratamento e prognóstico. Este estudo teve como objetivo caracterizar condições clínicas, gravidade, manejo e desfechos de pacientes com SHU. Materiais e Métodos: Estudo retrospectivo de pacientes com SHU admitidos numa Unidade de Nefrologia Pediátrica entre 1996-2020. Foram coletados dados demográficos e clínicos sobre etiologia, gravidade, estratégias de tratamento, desfechos de pacientes. Resultados: 29 pacientes com SHU foram admitidos em nossa unidade, mas quatro foram excluídos. A idade mediana ao diagnóstico foi dois anos (2 meses-17 anos). Manifestações clínicas incluíram diarreia, vômitos, oligúria, hipertensão e febre. Durante a fase aguda, 14 pacientes (56%) necessitaram de terapia renal substitutiva. Identificou-se a etiologia infecciosa em sete pacientes (cinco Escherichia coli; dois Streptococcus pneumoniae). Desde 2015, 2/7 pacientes foram diagnosticados com SHU por desregulação da via do complemento e não foram detectados casos de etiologia infecciosa. Seis desses pacientes receberam eculizumab. A mediana global de acompanhamento foi 6,5 anos [3 meses-19,8 anos]. Um paciente faleceu, sete apresentaram doença renal crônica, sendo quatro submetidos a transplante renal, uma recidiva e sete sem sequelas. Conclusão: Estes resultados refletem a ausência de surtos infecciosos em Portugal e a melhoria na identificação etiológica desde que os testes genéticos foram introduzidos. A maioria dos pacientes desenvolveu sequelas e a mortalidade foi semelhante à de outros países. Pacientes com SHU devem ser manejados em centros com cuidados intensivos e nefrologia pediátrica com capacidade para diagnóstico, investigação etiológica e tratamento adequado. O acompanhamento alongo prazo é essencial.

Síndrome urémico hemolítico del adulto / Adult hemolytic uremic syndrome

El síndrome urémico hemolítico (SUH), descripto en 1955, se caracteriza por la tríada de anemia hemolítica no inmunomediada, trombocitopenia y lesión renal aguda. En su patogenia interviene la toxina Shiga, producida con mayor frecuencia por E. coli O157:H. Puede manifestarse a cualquier edad, aunque es infrecuente en adultos, y se desarrolla en forma esporádica o en brote. Se presenta con un cuadro de dolor abdominal, diarrea, fiebre y vómitos. Puede afectar el sistema nervioso central, pulmones, páncreas y corazón. En adultos, el síndrome evoluciona tras un período de incubación de 1 semana posterior a la diarrea y tiene alta morbimortalidad, a diferencia de los casos pediátricos. Presentamos el caso de una paciente adulta, que cursó internación por síndrome urémico hemolítico. (AU)

Hemolytic uremic syndrome (HUS), described in 1955, is characterized by the triad of non-immune mediated hemolytic anemia, thrombocytopenia, and acute kidney injury. Shiga toxin, produced most frequently by E coli O157:H, is involved in its pathogenesis. Hus can manifest at any age, although it is rare in adults and develops sporadically or in outbreaks. HUS presents with a picture of abdominal pain, diarrhea, fever and vomiting. It can affect the central nervous system, lungs, pancreas, and heart.In adults, the syndrome evolves after an incubation period of 1 week after diarrhea, with high morbidity and mortality, unlike pediatric cases.We present the case of an adult patient who was hospitalized for hemolytic uremic syndrome. (AU)

Atypical hemolytic uremic syndrome in a patient with HIV treated with eculizumab: A case report.

Thrombotic microangiopathy defines a group of pathologies characterized by microvascular dysfunction with the concurrence of microangiopathic hemolytic anemia, thrombocytopenia, and organ damage. It represents the most frequent microvascular manifestation of human immunodeficiency virus (HIV) infection. We report the case of a man in the seventh decade of life with a recent diagnosis of infection by HIV, who develops hemolytic uremic syndrome, requiring continuous renal replacement therapy and plasma replacement therapy, without response, ADAMTS13 with preserved activity, ruling out other etiologies (infectious, metabolic, and genetic) with successful response to eculizumab.

Hyperuricemia: an unrecognized risk factor for kidney-related sequelae in children with hemolytic uremic syndrome.

BACKGROUND: Chronic kidney-related sequelae after STEC-HUS occur in 20-40% of patients. Hyperuricemia (HU) may cause acute and chronic toxicity involving the kidneys. We retrospectively assessed if there was an association between the presence of HU during the acute illness and that of kidney-related sequelae in children with STEC-HUS. METHODS: Children with STEC-HUS who had clinical and laboratory data at 2 years of follow-up were included in this case-control study. Univariate and multivariate analyses were performed between patients with (cases) or without (controls) kidney-related sequelae to identify factors associated with outcomes, including different measures of serum uric acid (sUA) (baseline level, peak, and duration of HU). HU was defined as sUA > 8 mg/dL. RESULTS: Of 86 patients included, 77.9% had HU. Patients with sequelae (n = 41) had a higher prevalence of HU (41/41 vs. 26/45, p < 0.01), higher baseline leukocyte count, serum creatinine (sCr), and sUA levels as well as lower sodium than controls. During hospitalization, cases also had higher sCr peak, sUA peak and duration of HU, requirement and duration of dialysis, extrarenal complications, and hypertension. By multivariate analysis, after adjusting for length of dialysis, only duration of HU (p = 0.0005; OR 1.7, 95% CI 1.27-2.36) remained as an independent predictor of sequelae, with a best cutoff of 5.5 days (AUC 0.95, specificity 80%, sensitivity 100%). CONCLUSIONS: The presence of HU is a common finding in children with STEC-HUS and its duration during the acute stage was associated with kidney-related sequelae, regardless of the duration of dialysis. A higher resolution version of the Graphical abstract is available as Supplementary Information.

HUS with mutations in CFH and STEC infection treated with eculizumab in a 4-year-old girl.

BACKGROUND: Hemolytic uremic syndrome secondary to Shiga-toxin-producing Escherichia coli infection (STEC-HUS) generally shows a favorable outcome. Few cases develop extra-renal complications, since neurological involvement is an important cause of morbidity and mortality. The role of complement in STEC-HUS has been recently highlighted, and the use of eculizumab in severe cases has been communicated. HUS results from environmental and genetic factors, but the simultaneous occurrence of STEC and complement mutations remains undetermined. METHODS: A pediatric case with severe STEC-HUS carrying CFH mutations, with favorable response to eculizumab is analyzed. RESULTS: STEC-HUS was diagnosed in a 4-year-old girl with classic HUS, including low C3. Peritoneal dialysis was started due to hypertension, oligoanuria, and pleural effusion. She evolved with generalized tonic-clonic seizures and required mechanical ventilation. MRI reported multiple supra- and infratentorial ischemic lesions with laminar/striatal cortical necrosis and leukoencephalopathy. After two eculizumab doses, a significative stabilization in diuresis, blood pressure, creatinine, and C3 was achieved. At the third week, episodes of massive digestive bleeding and a life-threatening condition required a colectomy thus preserving the ileocecal valve. Due to atypical evolution, a genetic study was considered, identifying two heterozygous variants (CFH S1191L/V1197A). CONCLUSION: STEC-HUS in patients with a genetic predisposition has been previously reported, but the low frequency of occurrence makes it a rare disease. As in the present case, patients with atypical course might benefit from genetic analysis to evaluate early eculizumab initiation and to better understand its phenotype. A higher resolution version of the Graphical abstract is available as Supplementary information.

Síndrome urémico hemolítico: reporte de dos casos pediátricos con nexo epidemiológico / Hemolytic uremic syndrome: report of two pediatric clinical cases with epidemiologic link / Síndrome urémico hemolítico: reporte de casos pediátricos con nexo epidemiológico

Introducción: el síndrome hemolítico urémico (SHU) es en muchos países, de las causas más frecuentes de insuficiencia renal aguda. La mayoría de los casos ocurre luego de un episodio de gastroenteritis aguda (GEA) por Escherichia coli productora de toxina Shiga (STEC). En Uruguay a pesar de ser una enfermedad de notificación obligatoria, existe subregistro. Objetivo: describir dos casos clínicos de SHU asociados a GEA con nexo epidemiológico. Casos clínicos: se trata de dos varones de 4 y 5 años, sanos. En los días previos, ingesta de carne en el mismo local comercial. Consultaron por dolor abdominal, deposiciones líquidas y vómitos reiterados. El niño de 4 años presentaba fiebre y deposiciones líquidas con sangre. El niño de 5 años dolor abdominal. El estado de hidratación y las constantes vitales eran normales en ambos. Fueron admitidos a cuidados moderados. A las 48 horas y a los 5 días, respectivamente, agregan palidez cutáneo-mucosa intensa, edemas y oliguria. Estudios complementarios: anemia, plaquetopenia e insuficiencia renal. Ingresaron a cuidados intensivos y se realizó diálisis peritoneal. La investigación de STEC fue negativa y la evolución favorable. Conclusiones: en menores de 5 años el SHU asociado a GEA es la forma de enfermedad más frecuente. En Uruguay predominan las cepas STEC no-O157. En estos casos no se pudo identificar el agente. La existencia de un nexo epidemiológico alerta sobre la necesidad de extremar los cuidados en la preparación y cocción de la carne. Debido a la asociación con una enfermedad prevalente, es necesario tener presente esta complicación para poder sospecharla e iniciar el tratamiento en forma precoz y oportuna.

Introduction: hemolytic uremic syndrome (HUS) is one of the most frequent causes of acute renal failure in many countries. Most cases occur after an episode of acute gastroenteritis (GEA) due to the Shiga toxin producing Escherichia Soli (STEC). In Uruguay, despite being a disease that requires mandatory notification, it is under reported. Objective: to describe two clinical cases of HUS associated with GEA with an epidemiological link. Clinical cases: these are two healthy boys aged 4 and 5 years. In the previous days, they reported meat intake in the same commercial premises. They consulted for abdominal pain, liquid stools and repeated vomiting. The 4 year old boy had a fever and bloody stools. The 5 year old boy had abdominal pain. They both showed normal hydration levels and vital signs. They were admitted to moderate care. At 48 hours and 5 days, respectively, they showed intense skin and mucosal paleness, edema and oliguria. Complementary studies: anemia, thrombocytopenia and renal failure. They were admitted to intensive care and peritoneal dialysis was performed. The STEC's investigation was negative and the evolution favorable. Conclusions: in children under 5 years of age, HUS associated with GEA is the most frequent form of the disease. In Uruguay, non-O157 STEC strains predominate. In these cases, the agent could not be identified. The existence of an epidemiological link warns us about the need for extreme care in the preparation and cooking of meat. Due to the association with a prevalent disease, it is necessary to keep this complication in mind in order to suspect it and initiate early and timely treatment.

Introdução: a síndrome hemolítico urêmica (SHU) é uma das causas mais frequentes de insuficiência renal aguda em muitos países. A maioria dos casos ocorre após um episódio de gastroenterite aguda (GEA) devido à Escherichia Coli, a toxina produtora de Shiga (STEC). No Uruguai, apesar de ser uma doença de notificação compulsória, há subnotificação. Objetivo: descrever dois casos clínicos de SHU associada à AGE com vínculo epidemiológico. Casos clínicos: dois meninos saudáveis com idades entre 4 e 5 anos. Nos dias anteriores, eles reportaram consumo de carne nos mesmos estabe- lecimentos comerciais. Eles consultaram para dor abdominal, fezes líquidas e vômitos repetidos. O menino de 4 anos teve febre e fezes com sangue. O menino de 5 anos teve dores abdominais. O estado de hidratação e os sinais vitais foram normais em ambos meninos. Foram internados em cuidados moderados. Às 48 horas e 5 dias, respectivamente, apresentaram aliás palidez intensa da pele e mucosas, edema e oligúria. Realizaramse estudos complementares: anemia, trombocitopenia e insuficiência renal. Eles foram internados em terapia intensiva e realizouse diálise peritoneal. A investigação do STEC foi negativa e a evolução favorável. Conclusões: em crianças menores de 5 anos, a SHU associada à GEA é a forma mais frequente da doença. No Uruguai, predominam cepas STEC não-O157. Nesses casos, o agente não pôde ser identificado. A existência de um nexo epidemiológico alerta para a necessidade de extremo cuidado no preparo e cozimento da carne. Devido à associação com doença prevalente, é necessário considerar essa complicação para suspeitar e iniciar o tratamento precoce e oportunamente.

Manifestaciones hepatopancreáticas en síndrome hemolítico urémico atípico

Introducción: el síndrome hemolítico urémico atípico es una enfermedad severa y huérfana, la cual en su variedad atípica se presenta con manifestaciones clínicas extrarrenales y sistémicas. La presencia de afectación gastrointestinal es infrecuente, pero en los pacientes en los que se manifiesta el pronóstico desfavorable, dado que estos cursan con más recaídas y mayor mortalidad, por lo cual se hace indispensable que el personal de salud esté entrenado en detectar y reconocer las manifestaciones menos frecuentes de esta patología, para así impactar positivamente en el desenlace de estos pacientes. Objetivo: se busca ilustrar un caso singular en cuanto a la sintomatología presentada infrecuente por el paciente y sobre una etiología no descrita previamente en la literatura. Presentación del caso: se reporta el caso de un escolar masculino de 8 años que presentó fiebre, ictericia, dolor abdominal y lumbar, diarrea, hematemesis y hematuria, al cual se le diagnosticó síndrome hemolítico urémico atípico. El paciente presentó un rápido deterioro clínico con compromiso multiorgánico, documentándose hipertensión arterial y lesión renal aguda, que recibió manejo con cristaloides y diurético de asa sin mejoría, por lo que requirió inicio de terapia de reemplazo renal e incluso múltiple soporte transfusional; sin embargo, continuó sin mejoría clínica, por lo que se indicó inicio de anticuerpo monoclonal IgG humanizado recombinante con buenos resultados. Discusión y conclusión: este caso es un claro ejemplo de que la afectación extrarrenal y multiorgánica puede ser la manifestación principal de esta enfermedad, por lo que es importante que el clínico se encuentre sensibilizado y conozca los signos y los síntomas de la presentación atípica de esta patología, con el fin de evitar retrasos diagnósticos y terapéuticos. Asimismo, el abordaje etiológico es de suma importancia para brindar un pronóstico más preciso al paciente y su familia.

Introduction: Atypical hemolytic uremic syndrome is a severe and orphan disease, in its atypical variety courses with extrarenal clinical manifestations. The presence of gastrointestinal compromise is infrequent, but the prognosis is unfavorable, since they have more relapses and higher mortality. Therefore, it is important that physicians are trained in recognizing the rare manifestations of this pathology, in order to improve the outcome in these patients. Purpose: This case illustrates a unique case in terms of symptoms and etiology not previously described. Case presentation: We report the case of an 8-year-old male who presented with fever, jaundice, abdominal and lumbar pain, diarrhea, hematemesis, and hematuria. Atypical hemolytic uremic syndrome was diagnosed. He presented clinical deterioration with multiple organ involvement, documenting high blood pressure and acute kidney injury, who received management with crystalloids and diuretics without improvement, requiring renal replacement therapy and multiple transfusional support. However, there was still no clinical improvement, so the start of recombinant humanized IgG monoclonal antibody was indicated, with satisfactory outcomes. Discussion and conclusions: This case is a clear example that extrarenal and multi-organ involvement can be the main manifestation of this disease, so it is important that clinicians are aware of the clinical course that may develop a patient with atypical presentations, in order to avoid diagnostic and therapeutic delays. Likewise, the etiological approach is important in order to provide an accurate prognosis to the patient and his family.

Intestinal mucus-derived metabolites modulate virulence of a clade 8 enterohemorrhagic Escherichia coli O157:H7.

The human colonic mucus is mainly composed of mucins, which are highly glycosylated proteins. The normal commensal colonic microbiota has mucolytic activity and is capable of releasing the monosaccharides contained in mucins, which can then be used as carbon sources by pathogens such as Enterohemorrhagic Escherichia coli (EHEC). EHEC can regulate the expression of some of its virulence factors through environmental sensing of mucus-derived sugars, but its implications regarding its main virulence factor, Shiga toxin type 2 (Stx2), among others, remain unknown. In the present work, we have studied the effects of five of the most abundant mucolytic activity-derived sugars, Fucose (L-Fucose), Galactose (D-Galactose), N-Gal (N-acetyl-galactosamine), NANA (N-Acetyl-Neuraminic Acid) and NAG (N-Acetyl-D-Glucosamine) on EHEC growth, adhesion to epithelial colonic cells (HCT-8), and Stx2 production and translocation across a polarized HCT-8 monolayer. We found that bacterial growth was maximum when using NAG and NANA compared to Galactose, Fucose or N-Gal, and that EHEC adhesion was inhibited regardless of the metabolite used. On the other hand, Stx2 production was enhanced when using NAG and inhibited with the rest of the metabolites, whilst Stx2 translocation was only enhanced when using NANA, and this increase occurred only through the transcellular route. Overall, this study provides insights on the influence of the commensal microbiota on the pathogenicity of E. coli O157:H7, helping to identify favorable intestinal environments for the development of severe disease.

Text Mining of Biomedical Articles Using the Konstanz Information Miner (KNIME) Platform: Hemolytic Uremic Syndrome as a Case Study.

OBJECTIVES: Automated systems for information extraction are becoming very useful due to the enormous scale of the existing literature and the increasing number of scientific articles published worldwide in the field of medicine. We aimed to develop an accessible method using the open-source platform KNIME to perform text mining (TM) on indexed publications. Material from scientific publications in the field of life sciences was obtained and integrated by mining information on hemolytic uremic syndrome (HUS) as a case study. METHODS: Text retrieved from Europe PubMed Central (PMC) was processed using specific KNIME nodes. The results were presented in the form of tables or graphical representations. Data could also be compared with those from other sources. RESULTS: By applying TM to the scientific literature on HUS as a case study, and by selecting various fields from scientific articles, it was possible to obtain a list of individual authors of publications, build bags of words and study their frequency and temporal use, discriminate topics (HUS vs. atypical HUS) in an unsupervised manner, and cross-reference information with a list of FDA-approved drugs. CONCLUSIONS: Following the instructions in the tutorial, researchers without programming skills can successfully perform TM on the indexed scientific literature. This methodology, using KNIME, could become a useful tool for performing statistics, analyzing behaviors, following trends, and making forecast related to medical issues. The advantages of TM using KNIME include enabling the integration of scientific information, helping to carry out reviews, and optimizing the management of resources dedicated to basic and clinical research.