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1.
Transplant Proc ; 52(1): 146-152, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31924403

RESUMO

Atypical hemolytic uremic syndrome (aHUS) after kidney transplantation is rare and carries a grave outcome. We present a single-center experience of all aHUS cases since the program's inception. Six patients were diagnosed with aHUS, all after kidney transplants, except for 1 patient. All had nonreactive crossmatches. Delayed graft function (DGF) occurred in 2 patients. Five patients developed aHUS after transplant; 4 (80%) of these patients manifested aHUS ≤ 14 days. All were confirmed by allograft biopsy. Genetic testing was abnormal in all patients except for 1 patient. Actual patient and graft survival during the first year was 100% and 83.3%, respectively. A single graft was lost early in the study secondary to aHUS (eculizumab was not used in the treatment process). Prophylactic and therapeutic use of eculizumab salvaged all other cases. At 1 year, mean creatinine level was 1.9 mg/dL (range, 1.3-2.5). After 6 months of eculizumab treatment (halted in 2 cases) 1 patient had recurrence 2 months later and eculizumab was restarted. However, graft function continued to worsen, and the graft was ultimately lost at 20 months after kidney transplantation. High index of suspicion, prompt diagnosis, and utilization of eculizumab are key to successful salvage of allografts in cases of aHUS after kidney transplantation. aHUS can be prevented by prophylactic use of eculizumab. It still needs to be determined when and if eculizumab therapy can be safely discontinued.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Inativadores do Complemento/uso terapêutico , Transplante de Rim/efeitos adversos , Complicações Pós-Operatórias/tratamento farmacológico , Adulto , Síndrome Hemolítico-Urêmica Atípica/sangue , Síndrome Hemolítico-Urêmica Atípica/etiologia , Biópsia , Creatinina/sangue , Feminino , Sobrevivência de Enxerto , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/etiologia , Recidiva
2.
Obstet Gynecol ; 135(1): 46-58, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31809447

RESUMO

OBJECTIVE: To evaluate disease presentation, diagnosis, treatment, and clinical outcomes in pregnancy-associated atypical hemolytic uremic syndrome (aHUS). DATA SOURCES: We searched PubMed, MEDLINE, Cochrane Library, ClinicalTrials.gov, Web of Science, EMBASE and Google Scholar, from inception until March 2018. METHODS OF STUDY SELECTION: We included English-language articles describing aHUS in pregnancy or postpartum. The diagnosis of aHUS was characterized by hemolysis, thrombocytopenia, and renal failure and was distinguished from typical diarrhea-associated hemolytic uremic syndrome. Patients were excluded if individual data could not be obtained, the diagnosis was unclear, or an alternative etiology was more likely, such as thrombotic thrombocytopenic purpura or Shiga toxin-producing Escherichia coli. Reports were appraised by two reviewers, with disagreements adjudicated by a third reviewer. TABULATION, INTEGRATION, AND RESULTS: The search identified 796 articles. After review of titles, abstracts, and full text, we identified 48 reports describing 60 unique cases of pregnancy-associated aHUS, with 66 pregnancies. Twelve cases involved pregnancy in women with known aHUS, and 54 cases involved first-episode pregnancy-associated aHUS. Women with known aHUS, particularly those with baseline creatinine at or above 1.5 mg/dL, had a high rate of adverse pregnancy outcomes. For first-episode pregnancy-associated aHUS, diagnosis most often occurred postpartum (94%), after a cesarean delivery (70%), in nulliparous women (58%). Preceding obstetric complications were common and included fetal death, preeclampsia, and hemorrhage. Diagnosis was usually made clinically, based on the triad of microangiopathic hemolysis, thrombocytopenia, and renal failure. Additional testing included renal biopsy, complement genetic testing, and ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) testing. Treatment modalities included corticosteroids, plasma exchange, dialysis, and eculizumab. More women with first-episode pregnancy-associated aHUS achieved disease remission when treated with eculizumab, compared with those not treated with eculizumab (88% vs 57%, P=.02). CONCLUSION: Pregnancy-associated aHUS usually presents in the postpartum period, often after a pregnancy complication, and eculizumab is effective for achieving disease remission. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42019129266.


Assuntos
Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Síndrome Hemolítico-Urêmica Atípica/terapia , Complicações Hematológicas na Gravidez/diagnóstico , Complicações Hematológicas na Gravidez/terapia , Anticorpos Monoclonais Humanizados/uso terapêutico , Inativadores do Complemento/uso terapêutico , Feminino , Humanos , Troca Plasmática , Período Pós-Parto , Gravidez , Diálise Renal
3.
Eur J Ophthalmol ; 30(3): NP14-NP17, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-30841747

RESUMO

PURPOSE: To report a case of Purtscher-like retinopathy due to atypical hemolytic uremic syndrome and the changes seen in the optical coherence tomography angiography before and after treatment with eculizumab. CASE DESCRIPTION: A 22-year-old man with an unremarkable medical history presented with acute, bilateral blurred vision and headache of 1-week duration. Best corrected visual acuity of 20/50 and 20/40, respectively, in the patient's right eye and left eye. Funduscopy revealed multiple cotton-wool spots associated with intrarretinal fluid. Swept source optical coherence tomography revealed multifocal retinal detachments with increased choroidal thickness. Optical coherence tomography angiography showed areas of ischemia in both capillary plexus. Due to concurrent symptoms and laboratory analysis, he was diagnosed with atypical hemolytic uremic syndrome and secondary Purtscher-like retinopathy; therefore, treatment with eculizumab was initiated. After 2 months revascularization of the previous ischemic areas was seen in the optical coherence tomography angiography that were correlated with best corrected visual acuity improvement. CONCLUSION: Our findings suggest that evaluation of the macular capillary plexus revascularization by optical coherence tomography angiography during the disease could help to predict an improvement of best corrected visual acuity in these patients and the measurement of choroidal thickness could give us information about the resolution of the pathologic process.


Assuntos
Síndrome Hemolítico-Urêmica Atípica/complicações , Doenças Retinianas/diagnóstico , Doenças Retinianas/etiologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Inativadores do Complemento/uso terapêutico , Angiografia por Tomografia Computadorizada , Angiofluoresceinografia/métodos , Seguimentos , Humanos , Masculino , Doenças Retinianas/tratamento farmacológico , Tomografia de Coerência Óptica/métodos , Acuidade Visual , Adulto Jovem
5.
BMJ Case Rep ; 12(12)2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31811102

RESUMO

Atypical haemolytic uraemic syndrome (aHUS) is a rare, acquired thrombotic microangiopathy, mediated by complement activation, in very sick patients. Moyamoya is similarly a rare disease in which stenosis or occlusion of segment(s) of the anterior cerebral circulation leads to the formation of many thin collaterals. Other reports have described an association between HUS and Moyamoya disease in the paediatric population. However, this case study presents the exceptionally rare presentation of an adult with aHUS and Moyamoya disease in a patient who was treated with rituximab for marginal zone B-cell lymphoma.


Assuntos
Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Linfoma de Zona Marginal Tipo Células B/complicações , Doença de Moyamoya/complicações , Síndrome Hemolítico-Urêmica Atípica/diagnóstico por imagem , Síndrome Hemolítico-Urêmica Atípica/terapia , Terapia Combinada , Diagnóstico Diferencial , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade
6.
Iran J Kidney Dis ; 13(5): 316-321, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31705748

RESUMO

INTRODUCTION: Atypical hemolytic uremic syndrome (aHUS) is associated with mutations or antibodies that affect the regulation of the alternative complement pathway. In the recent years several studies have been published describing these mutations. In this study, the initial clinical findings, treatments and long-term follow-up results of 19 patients who were hospitalized with the diagnosis of aHUS were presented. MATERIALS AND METHODS: Nineteen patients who were diagnosed as aHUS were enrolled from January 2010 to March 2017. Initial clinical signs and clinical follow-up of patients with aHUS were evaluated. Disease causing complement factor H (CFH) mutations were determined.  Results. CFH mutations were detected in 5 of 19 aHUS cases. Of these, one was novel and 4 were previously reported. We reported here the clinical course of aHUS patients with CFH mutations (p.Glu936Asp, Val 1197Ala) and a novel mutation (Glu927Lys) which caused  previously defined aHUS. Two of the CFH mutation cases developed end stage kidney disease that required hemodialysis, 1 case developed chronic kidney disease. Two cases were in remission, one of them with supportive therapy and the other case was in remission with eculizumab treatment. CONCLUSIONS: Morbidity rate is higher in children with aHUS. The renal prognosis and morbidity rate is higher in children with CFH mutations than other children with aHUS. Poor prognosis in aHUS children with CFH mutation depends on the genetic background.


Assuntos
Síndrome Hemolítico-Urêmica Atípica/genética , Adolescente , Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome Hemolítico-Urêmica Atípica/etnologia , Síndrome Hemolítico-Urêmica Atípica/terapia , Criança , Pré-Escolar , Fator H do Complemento/genética , Inativadores do Complemento/uso terapêutico , Feminino , Humanos , Lactente , Falência Renal Crônica/etnologia , Falência Renal Crônica/genética , Falência Renal Crônica/terapia , Masculino , Diálise Renal , Estudos Retrospectivos , Resultado do Tratamento , Turquia/etnologia
7.
Obstet Gynecol ; 134(6): 1215-1218, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31764731

RESUMO

BACKGROUND: Untreated microangiopathic hemolytic anemia in pregnancy is associated with adverse maternal and perinatal outcomes. Accurate diagnosis is challenging owing to nonspecific clinical features and pathologic findings. Timely initiation of appropriate management is essential to optimize maternal and perinatal outcomes. CASE: A 26-year-old primiparous woman presented at 20 weeks of gestation with new-onset microangiopathic hemolytic anemia on a background of poorly controlled type 1 diabetes. She received eculizumab for presumed atypical hemolytic uremic syndrome. At 24 weeks of gestation, she developed superimposed early-onset preeclampsia; she delivered at 27 weeks of gestation after continuing eculizumab. CONCLUSION: Eculizumab may prolong pregnancy in early-onset preeclampsia. Additional research is needed to assess short-term and long-term maternal and newborn outcomes.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Diabetes Mellitus , Pré-Eclâmpsia/diagnóstico , Complicações na Gravidez , Diagnóstico Pré-Natal , Adulto , Anticorpos Monoclonais Humanizados/administração & dosagem , Síndrome Hemolítico-Urêmica Atípica/complicações , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Diagnóstico Diferencial , Feminino , Humanos , Pré-Eclâmpsia/tratamento farmacológico , Gravidez , Segundo Trimestre da Gravidez , Gravidez Prolongada
8.
Acta Med Port ; 32(10): 673-675, 2019 Oct 01.
Artigo em Português | MEDLINE | ID: mdl-31625881

RESUMO

The atypical hemolytic uremic syndrome comprises a thrombotic microangiopathy resulting from the complement alternate pathway hyperactivation. Its severity requires early diagnosis and treatment. The differential diagnosis includes typical hemolytic uremic syndrome (associated with Shiga toxin) and thrombotic thrombocytopenic purpura (associated with deficient activity of ADAMTS13). The only specific treatment currently available for atypical hemolytic uremic syndrome is eculizumab. We describe the case of a child with atypical hemolytic uremic syndrome diagnosed in the context of bloody diarrhea, complicated by neurological involvement that posed several diagnostic and therapeutic challenges.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Inativadores do Complemento/uso terapêutico , Criança , Diagnóstico Diferencial , Feminino , Síndrome Hemolítico-Urêmica/diagnóstico , Humanos , Púrpura Trombocitopênica Trombótica/diagnóstico , Púrpura Trombocitopênica Trombótica/etiologia
10.
Thromb Haemost ; 119(11): 1767-1772, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31587247

RESUMO

Thrombotic thrombocytopenic purpura (TTP) is a rare thrombotic microangiopathy (TMA) characterized by the severe deficiency of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) activity (< 10%). Rapid ADAMTS13 testing is crucial for an early diagnosis and optimal management of acute TTP. We evaluated the performance of the HemosIL AcuStar ADAMTS13 activity assay (Instrumentation Laboratory, Bedford, Massachusetts, United States), a fully automated chemiluminescent immunoassay with an analytical time of 33 minutes. A method comparison study was performed on 176 samples from 49 healthy donors and 127 TMA patients (109 TTP, 7 atypical hemolytic uremic syndrome, 11 other TMAs), comparing this new assay with an in-house FRETS-VWF73 assay and a commercial enzyme-linked immunosorbent assay (ELISA) (TECHNOZYM ADAMTS-13 Activity, Technoclone GmbH, Vienna, Austria). Agreement between methods was assessed with focus on ADAMTS13 activity less than 10%, the medical decision level relevant for TTP diagnosis. The HemosIL AcuStar ADAMTS13 Activity showed good correlation with both the FRETS-VWF73 (r = 0.96) and ELISA (r = 0.96) methods. Slope of the Passing-Bablok regression was 1.05 for FRETS-VWF73 and 1.02 for ELISA, and absolute bias at the medical decision level was +0.1 and +0.3%, respectively. The study also revealed high agreement with FRETS-VWF73 (kappa 0.97) and ELISA (kappa 0.98) methods in classifying TTP patients with a severe deficiency of ADAMTS13 activity. Because of its short turnaround time and full automation, the HemosIL AcuStar ADAMTS13 activity assay might become the assay of choice to rapidly test ADAMTS13 activity in plasma and thus establish the diagnosis of acute TTP in emergency settings.


Assuntos
Proteína ADAMTS13/sangue , Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Imunoensaio/métodos , Púrpura Trombocitopênica Trombótica/diagnóstico , Proteína ADAMTS13/deficiência , Síndrome Hemolítico-Urêmica Atípica/sangue , Síndrome Hemolítico-Urêmica Atípica/enzimologia , Automação Laboratorial , Biomarcadores/sangue , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Humanos , Medições Luminescentes , Valor Preditivo dos Testes , Púrpura Trombocitopênica Trombótica/sangue , Púrpura Trombocitopênica Trombótica/enzimologia , Reprodutibilidade dos Testes , Fatores de Tempo , Fluxo de Trabalho
11.
Am J Case Rep ; 20: 1460-1465, 2019 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-31582717

RESUMO

BACKGROUND Atypical hemolytic uremic syndrome (aHUS) is a genetic disorder with uncontrolled complement activation leading to systemic thrombotic microangiopathy; kidneys are almost invariably involved. Eculizumab has dramatically improved the prognosis of aHUS and affected women in the childbearing age are more likely to consider pregnancy, even if this could represent a risk for disease reactivation. Pregnancies in women with aHUS during Eculizumab treatment have been reported, with no cases of aHUS relapse. CASE REPORT We report the case of a female patient affected by aHUS with no specific gene mutations who had a pregnancy-associated aHUS relapse at 26-weeks of gestation during maintenance Eculizumab treatment. The patient developed stage II acute kidney injury and microangiopathic hemolytic anemia. Delivery by cesarean section at week 27, plasma exchange sessions and several supplemental Eculizumab administrations were required. After appropriate treatment, the patient partially recovered kidney function; the baby had a prolonged stay in the intensive care unit and showed no signs of neurologic damage. CONCLUSIONS Previous reports indicated that pregnancy-related aHUS relapses were unlikely in women undergoing Eculizumab treatment. Based on our case, we suggest caution in counselling pregnancy in women with aHUS treated with Eculizumab, especially in the absence of pathogenic mutations in complement-regulating genes. Clinicians should be aware of possible aHUS relapse in pregnancy during Eculizumab treatment.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome Hemolítico-Urêmica Atípica/complicações , Síndrome Hemolítico-Urêmica Atípica/terapia , Inativadores do Complemento/uso terapêutico , Complicações na Gravidez , Lesão Renal Aguda/classificação , Lesão Renal Aguda/etiologia , Lesão Renal Aguda/terapia , Adulto , Anemia Hemolítica/etiologia , Anemia Hemolítica/terapia , Cesárea , Feminino , Humanos , Troca Plasmática , Gravidez , Recidiva
12.
Medicine (Baltimore) ; 98(39): e17232, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31574834

RESUMO

RATIONALE: To report a rare case of severe atypical hemolytic-uremic syndrome (HUS) in a patient who presented with vitreous hemorrhage and tractional retinal detachment (TRD) in both eyes. To our knowledge, this is the first reported case of atypical HUS complicated with bilateral TRD in the literature. PATIENT CONCERNS: A 20-year-old man with atypical HUS demonstrated bilateral visual acuity of hand motion at 30 cm. DIAGNOSES: Dilated fundus examination revealed diffuse intraretinal hemorrhage with vascular engorgement, neovascularization of the disc, and neovascularization elsewhere bilaterally. Fluorescein angiography revealed bilateral proliferative retinopathy, retinal hemorrhage, and a large nonperfusion area with extensive neovascularization. Intravitreal antivascular endothelial growth factor (ranibizumab) injection was administered in both eyes, but his ophthalmic condition did not improve, and TRD developed bilaterally. Therefore atypical HUS complicated with bilateral TRD was diagnosed. INTERVENTIONS: Pars plana vitrectomy was performed with panretinal photocoagulation and silicone oil tamponade in the right eye. OUTCOMES: After the pars plana vitrectomy of right eye, the retina was well-attached after surgery, but visual acuity remained poor. Visual evoked potential examination showed poor waveforms bilaterally, which suggested ischemic optic neuropathy. LESSONS: Atypical HUS can cause systemic thrombotic microangiopathy, resulting in ischemic retinal changes. These ischemic retinal changes can then cause hypoxia, which triggers production of angiogenic factors and subsequently causes retinal vascular hyperpermeability, retinal and vitreous neovascularization, fibrovascular proliferation, vitreous hemorrhage, and TRD, in a manner similar to that of other ischemia-induced proliferative retinopathies. Despite successful surgery in the right eye, our patient's visual acuity did not improve, possibly because of severe and generalized ischemia of intraocular tissue, which resulted in ischemic optic neuropathy.


Assuntos
Síndrome Hemolítico-Urêmica Atípica/complicações , Descolamento Retiniano/etiologia , Hemorragia Vítrea/etiologia , Humanos , Masculino , Adulto Jovem
13.
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
14.
Kidney Blood Press Res ; 44(5): 1300-1305, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31522186

RESUMO

BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is a rare, life-threatening disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, and renal impairment caused by uncontrolled activation of the complement system. About 20% of patients show extrarenal manifestations, with central nervous system involvement being the most frequent. We described the clinical course and management of aHUS in an infant, that was caused by a complement 3 (C3) gene mutation with severe extrarenal manifestations. CASE PRESENTATION: A 4-month-old girl visited our hospital for jaundice and petechiae. Laboratory tests revealed microangiopathic hemolytic anemia, thrombocytopenia, and hyperazotemia. She was diagnosed with aHUS with a C3 p.E1160K mutation. Daily fresh-frozen plasma (FFP) therapy was administered; however, she experienced the severe extrarenal manifestations of pulmonary hemorrhage and gastrointestinal bleeding. With aggressive treatment, supportive care, and daily FFP transfusion, the patient recovered and was discharged after 72 days of hospital stay, on a regular FFP transfusion. Four months after diagnosis, she was switched to eculizumab treatment. Twenty months have passed since then and she has been relapse-free until now. CONCLUSION: aHUS is rare but has a devastating course if not properly treated. Severe extrarenal manifestations, such as pulmonary hemorrhage and gastrointestinal bleeding, can develop in aHUS caused by a C3 mutation. In our case, long-term management with eculizumab resulted in relapse-free survival.


Assuntos
Síndrome Hemolítico-Urêmica Atípica/complicações , Complemento C3/genética , Feminino , Humanos , Lactente , Mutação
15.
Adv Exp Med Biol ; 1165: 423-441, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31399977

RESUMO

Chronic kidney disease (CKD) is a public health problem worldwide, with increasing incidence and prevalence. The mechanisms underlying the progression to end-stage renal disease (ESRD) is not fully understood. The complement system was traditionally regarded as an important part of innate immunity required for host protection against infection and for maintaining host hemostasis. However, compelling evidence from both clinical and experimental studies has strongly incriminated complement activation as a pivotal pathogenic mediator of the development of multiple renal diseases and progressive replacement of functioning nephrons by fibrosis. Both anaphylatoxins, i.e., C3a and C5a, and membrane attack complex (MAC) contribute to the damage that occurs during chronic renal progression through various mechanisms including direct proinflammatory and fibrogenic activity, chemotactic effect, activation of the renal renin-angiotensin system, and enhancement of T-cell immunity. Evolving understanding of the mechanisms of complement-mediated renal injury has led to the emergence of complement-targeting therapeutics. A variety of specific antibodies and inhibitors targeting complement components have shown efficacy in reducing disease in animal models. Moreover, building on these advances, targeting complement has gained encouraging success in treating patients with renal diseases such as atypical hemolytic uremic syndrome (aHUS). Nevertheless, it still requires a great deal of effort to develop inhibitors that can be applied to treat more patients effectively in routine clinical practice.


Assuntos
Ativação do Complemento , Nefropatias/imunologia , Animais , Síndrome Hemolítico-Urêmica Atípica , Proteínas do Sistema Complemento , Fibrose , Humanos , Rim/patologia
16.
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
19.
BMJ Case Rep ; 12(6)2019 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-31253663

RESUMO

A 72-year-old woman was admitted to the hospital because of dorsal, lumbar and lower abdomen pain that had started 4 days before. She had a history of age-related macular degeneration (treated with intraocular bevacizumab). Blood tests showed anaemia, thrombocytopaenia, acute kidney injury, elevated liver enzymes and total bilirubin (mainly because of the indirect fraction). Viral serologies and ADAMTS13 activity levels were normal, and stool testing was negative for Escherichia coli-producing Shiga toxins. E. coli was isolated in urine. Atypical haemolytic uremic syndrome triggered by a urinary tract infection or by the vascular endothelial growth factor-inhibitor bevacizumab were the most likely hypothesis. The patient started urgent plasmapheresis and dialysis that lasted for a total of 18 days. There was complete remission and recovery of kidney function allowing for treatment discontinuation, and she was discharged home. After 6 months of follow-up, she shows no signs of relapse.


Assuntos
Síndrome Hemolítico-Urêmica Atípica/complicações , Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Infecções Urinárias/complicações , Idoso , Síndrome Hemolítico-Urêmica Atípica/terapia , Diagnóstico Diferencial , Feminino , Humanos , Plasmaferese/métodos , Diálise Renal/métodos , Infecções Urinárias/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/uso terapêutico
20.
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
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