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1.
BMJ Case Rep ; 12(9)2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31519719

RESUMO

Atypical haemolytic uraemic syndrome (aHUS) is a disease of complement dysregulation and can be fatal if not treated in a timely manner. Although normally associated with triggers such as infection or pregnancy, this case demonstrates acute pancreatitis as the triggering event. The patient's initial presentation of thrombocytopaenia and acute renal failure was first attributed to a systemic inflammatory response syndrome due to pancreatitis, but with detailed history and further laboratory investigation, we were able to show that patient was having symptoms associated with aHUS. On early recognition of aHUS, this patient was able to receive the proper standard of care with eculizumab and had a full recovery while preventing renal failure. When patients present with thrombocytopaenia and renal failure in acute pancreatitis, we want to ensure physicians keep aHUS on the differential.


Assuntos
Síndrome Hemolítico-Urêmica Atípica/etiologia , Pancreatite/complicações , Insuficiência Renal/etiologia , Trombocitopenia/etiologia , Doença Aguda , Adulto , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Inativadores do Complemento/administração & dosagem , Inativadores do Complemento/uso terapêutico , Diagnóstico Diferencial , Humanos , Masculino , Pancreatite/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
2.
Transplant Proc ; 51(7): 2295-2297, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31400975

RESUMO

PURPOSE: Hemolytic uremic syndrome (HUS) is characterized by microangiopathic anemia, thrombocytopenia, and acute kidney injury. HUS is mostly associated with diarrhea (90%). However, 10% of cases are not associated with diarrhea and are thus called as atypical HUS (aHUS); these cases are usually caused by dysregulation of the complement system. Eculizumab, a monoclonal antibody against C5, is the drug of choice for treating aHUS. Herein we aimed to present 8 cases of renal transplantation performed on patients with aHUS. MATERIALS AND METHODS: A total of 8 patients who had been diagnosed with aHUS between the years 2012 to 2018 were enrolled and underwent transplantations. All patients received induction treatment, standard immunosuppresive treatment (tacrolimus, mycophenolic acid, prednisolone), and eculizumab. Eculizumab was administered at a dosage of 900 mg/wk for the first month and 1200 mg every 2 weeks thereafter. Patients were followed up and recorded in terms of demographic features, serum creatinine, lactate dehydrogenase, acute rejection episodes, and allograft outcomes. RESULTS: Mean age was 34 ± 8 years (Male/Female: 6/2). One of the patients had a second transplantation. Median hemodialysis vintage (25%-75% interquartile range) was 37 (9-63) months. Four patients had pretransplant plasmapheresis and 2 patients had posttransplant plasmapheresis. Induction treatment was ATG in 7 patients, and basiliximab was used only in 1 patient. The median follow-up period was 25 (13-59) months. Mean serum creatinine levels were 1.9 ± .6, 1.2 ± .7, and 1 ± .1 mg/dL for the first day, first month, and last values, respectively. Mean lactate dehydrogenase levels were 286 ± 203, 239 ± 27, and 218 ± 86 U/L for first day, first month, and last values, respectively. None of the patients had an acute rejection episode. Currently, all patients have functioning allografts. CONCLUSION: Patients with aHUS may be transplanted successfully with eculizumab with good allograft outcomes.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Síndrome Hemolítico-Urêmica Atípica/cirurgia , Inativadores do Complemento/uso terapêutico , Transplante de Rim , Adulto , Terapia Combinada , Creatinina/análise , Feminino , Humanos , Masculino , Ácido Micofenólico/uso terapêutico , Plasmaferese , Período Pós-Operatório , Prednisolona/uso terapêutico , Tacrolimo/uso terapêutico , Resultado do Tratamento
3.
Brain Nerve ; 71(6): 555-564, 2019 Jun.
Artigo em Japonês | MEDLINE | ID: mdl-31171752

RESUMO

The complement was named after "a complement", a protein molecule that supports an antibody. It was considered previously that the complement mainly participates in protecting against microbial infections. But later, as research on biological functions in complement activation advanced drastically, it was elucidated that the complement could be involved in the onset of various diseases. In 2007, eculizumab (ECZ), an anti-C5 (complement factor 5) monoclonal antibody, was approved as a drug for paroxysmal nocturnal hemoglobinuria (PNH) in the United States. In Japan, ECZ was approved for PNH and atypical hemolytic uremic syndrome (aHUS) in 2010 and 2013, respectively. The success of ECZ created an opportunity for drug companies to develop new therapeutics targeting the complement system; development of complement therapeutics is now a major venture of pharmaceutical companies worldwide. Here, I will provide an outline of the approved complement therapeutics and those that are in development and clinical trial phase currently.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Inativadores do Complemento/uso terapêutico , Proteínas do Sistema Complemento , Hemoglobinúria Paroxística/tratamento farmacológico , Ensaios Clínicos como Assunto , Complemento C5/antagonistas & inibidores , Humanos , Japão
5.
Drugs ; 79(3): 347-352, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30767127

RESUMO

Ravulizumab (ravulizumab-cwvz; ULTOMIRIS™), a humanized monoclonal antibody, is a complement C5 inhibitor developed by Alexion Pharmaceuticals for the treatment of paroxysmal nocturnal haemoglobinuria (PNH) and atypical haemolytic uraemic syndrome (aHUS). Like the first-generation C5 inhibitor, eculizumab, ravulizumab binds specifically and with high affinity to the complement protein C5, thereby preventing formation of the terminal complement complex C5b-9, which mediates cell lysis. In December 2018, intravenous ravulizumab received its first global approval in the USA for the treatment of adults with PNH, and is under regulatory review in the European Union and Japan in this indication. Phase 3 development of intravenous ravulizumab for the treatment of aHUS is underway worldwide. The use of ravulizumab in myasthenia gravis and IgA nephropathy is also being evaluated in the USA in early-phase and preclinical studies, respectively. Clinical development of a subcutaneous formulation for PNH and aHUS is also underway. Ravulizumab has been developed using Xencor's antibody half-life prolongation technology (Xtend™), which utilises antibody Fc variants to prolong half-life. Alexion is also evaluating the coadministration of subcutaneous ravulizumab with Halozyme's ENHANZE® drug-delivery technology (rHuPH20), which may have the potential to further extend the dosing interval. This article summarizes the milestones in the development of ravulizumab leading to this first approval for PNH.


Assuntos
Anticorpos Monoclonais Humanizados/farmacologia , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Complemento C5/antagonistas & inibidores , Hemoglobinúria Paroxística/tratamento farmacológico , Aprovação de Drogas , Combinação de Medicamentos , Sistemas de Liberação de Medicamentos , Desenvolvimento de Medicamentos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estados Unidos , United States Food and Drug Administration
7.
BMJ Case Rep ; 12(1)2019 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-30659006

RESUMO

Pregnancy-induced atypical haemolytic uremic syndrome (P-aHUS) is a rare condition characterised by microangiopathic haemolytic anaemia, thrombocytopenia and renal failure. It accounts for approximately 7% of total HUS cases. Here, we present a case of recurrent P-aHUS in a 25-year-old Hispanic woman. Pregnancy was the clear trigger in both instances, and the disease manifested in first week of the postpartum period. Because of her significant obstetric history, a multidisciplinary approach was adopted to monitor her second pregnancy antepartum and post partum. As the patient developed recurrence of P-aHUS 4 days after her delivery, she was immediately administered eculizumab within few hours of disease manifestation. The patient normalised her haematological parameters within 1 week but sustained dialysis-requiring renal failure for a total of 6 weeks. This case highlights the advances as well as the ongoing uncertainties, especially with respect to the use of eculizumab, in this rare but morbid disease.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Complicações na Gravidez/tratamento farmacológico , Adulto , Síndrome Hemolítico-Urêmica Atípica/etiologia , Feminino , Humanos , Período Pós-Parto , Gravidez , Resultado do Tratamento
9.
J Oncol Pharm Pract ; 25(4): 1011-1015, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29768958

RESUMO

Bevacizumab (Avastin) is a recombinant humanized monoclonal antibody used for the management of various solid malignancies including colorectal, lung, brain, renal, and ovarian cancers as well as age-related macular degeneration of the eye. It is a vascular endothelial growth factor inhibitor which exhibits its action by blocking the growth of blood vessels in cancerous tissue. Common side effects include hypertension, fatigue, headaches, and increased risk of infections. Atypical hemolytic uremic syndrome is a serious side effect associated with bevacizumab due to its anti-angiogenic effect. It encompasses the clinical triad of thrombocytopenia, microangiopathic hemolytic anemia, and acute renal failure, without any association with Shiga toxins. Eculizumab is a terminal complement inhibitor used in the treatment of atypical hemolytic uremic syndrome. Herein, we present three cases of bevacizumab-induced atypical hemolytic syndrome treated successfully with eculizumab.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/efeitos adversos , Síndrome Hemolítico-Urêmica Atípica/induzido quimicamente , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Bevacizumab/efeitos adversos , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Idoso , Feminino , Humanos , Pessoa de Meia-Idade
10.
J Matern Fetal Neonatal Med ; 32(17): 2853-2859, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29606012

RESUMO

Objective: The aim of this case series is to raise awareness of obstetric-related atypical haemolytic uraemic syndrome (aHUS) amongst obstetricians and gynaecologists. Study design: Data from 20 consecutive patients, aged 19-38, with obstetric-aHUS manifestation during or immediately after pregnancy are reported. Patients were diagnosed and treatment was initiated between 2012 and 2016. Results: Presentation of aHUS was mainly preceded by preeclampsia and/or haemolysis, elevated liver enzymes and low platelet count syndrome, other obstetric complications, or by diarrhoea. Thrombotic microangiopathy (TMA) was evident in all patients with signs of microangiopathic haemolysis (sharp decline in haemoglobin; mean 67 g/L), elevated lactate dehydrogenase (LDH; mean 2953.1 U/L), schistocytosis, thrombocytopenia (mean platelet count 52.5 × 109/µL), and acute kidney injury (AKI) (hypercreatininaemia, mean 456.4 µmol/L; oliguria or anuria). The majority of patients (80%) initially presented with arterial hypertension. Diagnosis of obstetric-aHUS was complicated, as multiple organs were affected. Time taken to make the diagnosis of aHUS delayed the initiation of fresh-frozen plasma infusions and plasma exchange (80% of patients) and subsequent eculizumab treatment (40% of patients). Maternal mortality was high (35%) as was foetal mortality (25%). Conclusions: Obstetric-aHUS is a serious condition characterized by multiple organ failure (MOF) and a high mortality rate. Presentation of obstetric-aHUS is preceded by various precipitating factors, suggesting pregnancy complications, and not the pregnancy per se, often induce aHUS in women with a genetic predisposition to its development. A delay in the correct diagnosis and initiation of the most effective treatment can have serious consequences, reinforcing the need to raise awareness of obstetric-aHUS.


Assuntos
Síndrome Hemolítico-Urêmica Atípica/mortalidade , Insuficiência de Múltiplos Órgãos/etiologia , Complicações na Gravidez/mortalidade , Lesão Renal Aguda/etiologia , Lesão Renal Aguda/mortalidade , Adulto , Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome Hemolítico-Urêmica Atípica/sangue , Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Inativadores do Complemento/uso terapêutico , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Insuficiência de Múltiplos Órgãos/mortalidade , Morte Perinatal , Gravidez , Complicações na Gravidez/sangue , Complicações na Gravidez/diagnóstico , Complicações na Gravidez/tratamento farmacológico , Adulto Jovem
11.
J Pediatr Hematol Oncol ; 41(2): e111-e113, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-29750742

RESUMO

We present the case of a 2-month-old infant presenting with pallor and laboratory results showing: hemoglobin 5.1 (10 to 1.5) g/dL, MCV 94.7 (75 to 105) fL, leukocytes 17.4 (7 to 15) ×10/µL, platelets 259 (150 to 450) ×10/µL, hyperbilirubinemia and renal dysfunction. A hemolytic anemia with tubular injury secondary to hemoglobinuria was suspected. Hyperhydration and packed cells were given but she deteriorated. Fluid overload with anuria further complicated the course necessating hemodialysis. Atypical hemolytic uremic syndrome was suspected and eculizumab was administered resulting in rapid improvement. Genetic analysis revealed a mutation in the gene encoding complement factor H and atypical hemolytic uremic syndrome was confirmed.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Síndrome Hemolítico-Urêmica Atípica , Mutação , Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Síndrome Hemolítico-Urêmica Atípica/genética , Síndrome Hemolítico-Urêmica Atípica/patologia , Fator H do Complemento/genética , Feminino , Humanos , Lactente
12.
Clin Exp Nephrol ; 23(1): 65-75, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29959568

RESUMO

BACKGROUND: Eculizumab has been available for the treatment of atypical hemolytic-uremic syndrome (aHUS) in Japan since 2013. To assess safety and effectiveness of eculizumab in adult aHUS patients in the real-life setting, we performed interim analysis of a post-marketing surveillance mandated by Japanese regulations. METHODS: This study enrolled any patient who was diagnosed with TMA excluding Shiga toxin-producing Escherichia coli-HUS or thrombotic thrombocytopenic purpura based on Japanese clinical guide published in 2013 as inclusion criteria and treated with eculizumab. Although the term aHUS was redefined to denote only complement-mediated HUS in the guide revised in 2016, the patients with TMA caused by other causes (secondary TMA) were included. Patient outcomes and safety were evaluated at 6 months, 12 months, and annually thereafter. RESULTS: Thirty-three patients with aHUS and 27 patients with secondary TMA were enrolled. Median treatment duration of aHUS was 24weeks. Complement genes variants were detected in 11 of 18 patients with aHUS (61.1%). Among the 29 aHUS patients with available baseline data, platelet count (PLT), lactic dehydrogenase and serum creatinine (SCr) improved within 1-month after eculizumab initiation. TMA event-free status, complete TMA response, PLT normalization, and SCr decrease were achieved in 67.9% (19/28), 27.8% (5/18), 56.5% (13/23), and 57.1% (16/28) of patients, respectively. Thirty-three and 11 adverse reactions were observed in patients with aHUS (13/33 patients) and secondary TMA (6/27 patients), respectively. CONCLUSIONS: This interim analysis confirmed the acceptable safety profile and effectiveness of eculizumab for Japanese adult aHUS patients in real-world settings.


Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Inativadores do Complemento/efeitos adversos , Inativadores do Complemento/uso terapêutico , Adulto , Idoso , Síndrome Hemolítico-Urêmica Atípica/genética , Complemento C5/antagonistas & inibidores , Proteínas do Sistema Complemento/genética , Feminino , Variação Genética/genética , Humanos , Japão , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Segurança do Paciente , Vigilância de Produtos Comercializados , Resultado do Tratamento , Adulto Jovem
13.
Clin Exp Nephrol ; 23(1): 112-121, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30039480

RESUMO

BACKGROUND: In 2013, eculizumab was approved for treatment of the atypical hemolytic-uremic syndrome (aHUS) in Japan, which was defined as a thrombotic microangiopathy (TMA) excluding Shiga toxin-producing Escherichia coli-HUS and thrombotic thrombocytopenic purpura. Simultaneously, post-marketing surveillance was started to assess its safety and effectiveness. In 2016, Japanese clinical guide redefined terms to limit the use of "aHUS" to complement-mediated HUS only. Accordingly, TMA with other causes was defined as secondary TMA. Here we report the interim analysis of post-marketing surveillance of pediatric patients with aHUS and secondary TMA. METHODS: Pediatric patients treated with eculizumab from approval to 15 March 2017 were included in this observational real-world study. Clinical endpoints of effectiveness were TMA event-free status, complete TMA response, platelet count normalization, and improvement of estimated glomerular filtration rate (eGFR). Adverse reactions to eculizumab were also analyzed. RESULTS: In 27 pediatric patients with aHUS, median age at diagnosis was 4 years. Complement genes' variants were detected in 14 of 21 patients (66.7%). Median time from diagnosis to eculizumab initiation was 2.0 days. TMA event-free status, complete TMA response, platelet normalization, and improvement in eGFR were achieved in 85.2, 36.4, 78.3, and 75.0% of patients, respectively. Three patients with aHUS died. Twenty-four and 10 adverse reactions were reported in 31 aHUS patients and 17 secondary TMA patients, respectively; however, no eculizumab-related death or meningococcal infection was reported. CONCLUSIONS: This interim analysis confirmed that eculizumab is well-tolerated and effective for Japanese pediatric patients with aHUS in a real-world setting.


Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Inativadores do Complemento/efeitos adversos , Inativadores do Complemento/uso terapêutico , Adolescente , Síndrome Hemolítico-Urêmica Atípica/genética , Criança , Pré-Escolar , Complemento C5/antagonistas & inibidores , Proteínas do Sistema Complemento/genética , Feminino , Variação Genética/genética , Taxa de Filtração Glomerular , Humanos , Lactente , Recém-Nascido , Japão , Testes de Função Renal , Masculino , Segurança do Paciente , Contagem de Plaquetas , Vigilância de Produtos Comercializados , Resultado do Tratamento
14.
Hematology Am Soc Hematol Educ Program ; 2018(1): 371-376, 2018 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-30504334

RESUMO

Atypical hemolytic uremic syndrome (aHUS); hemolysis, elevated liver function tests, and low platelets syndrome; and transplant-associated thrombotic microangiopathy are related conditions, in that many patients harbor germline heterozygous mutations in genes that regulate the alternative pathway of complement (APC). Penetrance is variable because development of clinically significant disease appears to require supervention of a process such as inflammation. Complement activation on the endothelial surfaces leads to endothelial damage, platelet consumption, microthrombi, and a mechanical hemolytic anemia with schistocytes. Paroxysmal nocturnal hemoglobinuria (PNH) is a clonal hematopoietic disease caused by expansion of a stem cell that harbors a somatic mutation in PIGA PIGA mutant blood cells are deficient in the complement regulator proteins CD55 and CD59, making them susceptible to intravascular hemolysis due to a failure to regulate the APC on erythrocytes. Eculizumab is a monoclonal antibody that binds to C5 and inhibits terminal complement by interfering with the cleavage of C5 by the C5 convertases. The drug is approved by the US Food and Drug Administration for the treatment of aHUS and PNH; however, a new generation of complement inhibitors that block C5 and other components of the complement cascade is showing promise in preclinical and clinical trials.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome Hemolítico-Urêmica Atípica , Hemoglobinúria Paroxística , Mutação , Síndrome Hemolítico-Urêmica Atípica/sangue , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Síndrome Hemolítico-Urêmica Atípica/genética , Antígenos CD55/sangue , Antígenos CD55/genética , Antígenos CD59/sangue , Antígenos CD59/genética , Complemento C5/antagonistas & inibidores , Complemento C5/genética , Complemento C5/metabolismo , C5 Convertase da Via Alternativa do Complemento/antagonistas & inibidores , C5 Convertase da Via Alternativa do Complemento/genética , C5 Convertase da Via Alternativa do Complemento/metabolismo , Via Alternativa do Complemento/efeitos dos fármacos , Via Alternativa do Complemento/genética , Hemoglobinúria Paroxística/sangue , Hemoglobinúria Paroxística/tratamento farmacológico , Hemoglobinúria Paroxística/genética , Hemólise/efeitos dos fármacos , Hemólise/genética , Humanos , Proteínas de Membrana/sangue , Proteínas de Membrana/genética , Penetrância
15.
Pol Merkur Lekarski ; 45(267): 119-121, 2018 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-30240381

RESUMO

Atypical hemolytic uremic syndrome (aHUS) is an extremely rare disease characterized by acute kidney injury, thrombocytopenia, and microangiopathic hemolytic anemia. Majority of patients have an underlying complement abnormality what makes aHUS possible to treat using eculizumab, antibody against the complement protein C5. Up to 2018, Polish adult patients were treated using glucocorticosteroids, plasma exchange or plasma infusion. Unfortunately, such protocols/ interventions were associated with poor prognosis; about 67% of adult patients with aHUS had been progressing to end-stage renal disease or had died within three years after diagnosis. Release of eculizumab significantly improve the prognosis of aHUS. We describe new drug program and case of first included adult patient: after ineffective nonspecific treatment of aHUS with plasma infusions (10 units), plasma exchanges (7 sessions) and glucocorticosteroids, we decided to introduce eculizumab. The clinical and laboratory tests showed effectiveness of the therapy after sixth infusion; no adverse effects were observed.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Adulto , Feminino , Humanos , Polônia , Resultado do Tratamento
16.
Saudi J Kidney Dis Transpl ; 29(4): 967-970, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30152436

RESUMO

Atypical hemolytic-uremic syndrome (aHUS) can pose a diagnostic challenge due to the multisystem involvement and varied manifestations. Early diagnosis and initiation of Eculizumab have been reported to have favorable renal outcomes. We report a case of 11-month-old male infant who presented at the age of two months with anemia, acute kidney injury, hypertension, and nephromegaly. Renal biopsy confirmed the diagnosis of aHUS and Eculizumab was started. Thrombotic microangiopathy markers showed the resolution. Kidney sizes improved after nine months of Eculizumab therapy. The successful resolution of nephromegaly in an infant with aHUS has not been reported so far in literature. Renal sizes should be monitored in all children with aHUS.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome Hemolítico-Urêmica Atípica , Nefropatias , Rim/patologia , Síndrome Hemolítico-Urêmica Atípica/complicações , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Humanos , Hipertensão/complicações , Lactente , Nefropatias/complicações , Nefropatias/diagnóstico , Masculino
17.
Am J Nephrol ; 48(2): 96-107, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30110670

RESUMO

The terminal complement-inhibitor eculizumab has dramatically changed the management of patients with atypical hemolytic uremic syndrome (aHUS), and has also shown promise for treating certain forms of secondary HUS (sHUS), including that caused by drugs and solid-organ/hematopoietic stem cell transplant. While effective, eculizumab is costly and inconvenient. In this review, we evaluate the literature on eculizumab cessation in these diseases to better inform clinicians who consider stopping therapy. Reported relapse rates in aHUS after stopping eculizumab are as high as 30%, suggesting indefinite therapy is reasonable and that patients who choose to stop should be closely monitored. In sHUS, relapse is rare, justifying short courses of eculizumab.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Inativadores do Complemento/uso terapêutico , Guias de Prática Clínica como Assunto , Suspensão de Tratamento/normas , Anticorpos Monoclonais Humanizados/economia , Síndrome Hemolítico-Urêmica Atípica/economia , Inativadores do Complemento/economia , Inativadores do Complemento/normas , Humanos , Recidiva , Fatores de Tempo , Suspensão de Tratamento/economia
18.
Rev Med Chil ; 146(2): 254-259, 2018 Feb.
Artigo em Espanhol | MEDLINE | ID: mdl-29999163

RESUMO

Hemolytic uremic syndrome (HUS) is a type of thrombotic microangiopathy where organic damage predominates in the kidney. Atypical HUS (aHUS) is a rare disease that affects young adults and causes terminal chronic renal failure ending in dialysis, in most cases. It also recurs after kidney transplantation. aHUS is associated with genetic defects of the alternative complement pathway or its activation by other factors such as drugs, autoimmune diseases, infections, malignant hypertension and ischemia-reperfusion. We report two women aged 17 and 25 years old with catastrophic aHUS. In both cases, complement amplifying factors (drugs and infections) were added and acted on a genetic vulnerability to precipitate complement activation and produce aHUS. Both patients developed terminal renal failure and had to undergo hemodialysis. Fortunately, after a broad etiological study, it was possible to make the diagnosis of aHUS and start treatment with Eculizumab, a monoclonal antibody that changed the natural history of aHUS. It inhibits complement activity controlling microangiopathy and preventing the development of end-stage renal disease. It also improves the success rate in kidney transplantation. In the case of our patients, both discontinued dialysis after chronic treatment with Eculizumab.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Adolescente , Adulto , Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Feminino , Seguimentos , Humanos
19.
Internist (Berl) ; 59(8): 799-804, 2018 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-29995248

RESUMO

The atypical hemolytic uremic syndrome (aHUS), one of the three major forms of thrombotic microangiopathy, is characterized by genetic alterations in the area of the complement cascade, which can be detected in 40%-60% of all patients with aHUS. Mutations in over 10 different genes have now been identified. The most frequent and clinically relevant of these are mutations that result in a decreased or absent function of factor H, the formation of hybrid genes, or the formation of autoantibodies against factor H. Although genetics are not required for the diagnosis of aHUS, it is of great importance for the decision on how long to treat with the C5 inhibitor eculizumab. Also, knowledge of genetic alterations is absolutely essential if a living related donor is considered, in order to protect the living donor and recipient from developing aHUS.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Complemento C5/uso terapêutico , Mutação/genética , Síndrome Hemolítico-Urêmica Atípica/genética , Complemento C5/antagonistas & inibidores , Fator H do Complemento/imunologia , Genética Humana , Humanos
20.
Semin Hematol ; 55(3): 150-158, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-30032752

RESUMO

The dissection of the pathogenic mechanisms of the various forms of the hemolytic uremic syndrome (HUS) has paved the way for the design of specific efficacious treatments. Such mechanistic approach led to a revolution in the management of atypical HUS with the use of the first-in class C5 blocker, eculizumab. The availability of this anticomplement drug has also raised unsettled questions regarding the cost or burden and optimal duration of therapy and its use in secondary HUS. The efficacy of eculizumab in Shiga toxin producing Escherichia coli-associated HUS is not to date established and the results of ongoing prospective studies are eagerly awaited. Nevertheless, the emergence of anticomplement therapies (eculizumab and other drugs in development) has transformed our approach of HUS.


Assuntos
Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Proteínas Inativadoras do Complemento/uso terapêutico , Síndrome Hemolítico-Urêmica Atípica/patologia , Proteínas Inativadoras do Complemento/farmacologia , Humanos , Resultado do Tratamento
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