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1.
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
2.
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
3.
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
4.
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
5.
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
6.
Saudi J Kidney Dis Transpl ; 30(3): 701-705, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31249236

RESUMO

In evaluating a patient with thrombotic microangiopathy (TMA), it is necessary to rule out thrombotic thrombocytopenic purpura before a diagnosis of atypical hemolytic uremic syndrome (aHUS) is made. There have been reports that mutations of complement factors can coexist with partial A Disintegrin and Metalloproteinase with a ThromboSpondin type 1 motif, member 13 deficiency. Here, we report the case of a 6-year-old girl who was initially diagnosed as nephrotic syndrome and developed TMA after five years of onset of illness. She had poor response to treatment and had multiple relapses due to associated complement factor mutation. Hence, genetic evaluation has to be considered in all children presenting with aHUS.


Assuntos
Proteína ADAMTS13/genética , Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Proteínas do Sistema Complemento/genética , Mutação , Púrpura Trombocitopênica Trombótica/diagnóstico , Proteína ADAMTS13/deficiência , Síndrome Hemolítico-Urêmica Atípica/genética , Síndrome Hemolítico-Urêmica Atípica/imunologia , Síndrome Hemolítico-Urêmica Atípica/terapia , Criança , Proteínas do Sistema Complemento/imunologia , Diagnóstico Diferencial , Evolução Fatal , Feminino , Predisposição Genética para Doença , Humanos , Fenótipo , Valor Preditivo dos Testes , Púrpura Trombocitopênica Trombótica/genética , Púrpura Trombocitopênica Trombótica/terapia , Resultado do Tratamento
7.
J Clin Apher ; 34(5): 555-562, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31173399

RESUMO

BACKGROUND: While complement blockade with eculizumab is recommended as first-line therapy of atypical hemolytic uremic syndrome (aHUS), plasma exchanges (PEX) remain the chief option for anti-factor H (FH) antibody associated disease and when access to eculizumab is limited. METHODS: We reviewed adverse events (AEs) and adverse outcomes (eGFR <30 mL/min/1.73 m2 or death), in all patients with aHUS managed with membrane-filtration based PEX at one tertiary care center over 5.5 years. RESULTS: During January 2013 to June 2018, 109 patients with aHUS (74 with antibodies to FH), aged median (range) 7.6 (0.5-18) year weighing 22.1 (6-90) kg, underwent 2024 sessions of PEX. AE, in 12.1% patients, were usually self-limiting and included chills (5.5%), vomiting/abdominal pain (3.3%), hypotension (1.6%), urticaria (1.5%), seizures (0.2%), hypocalcemia (0.2%), and hemorrhage (0.1%); plasma hypersensitivity and severe reactions were rare. Rate of catheter-related infections was 1.45/1000 catheter-days. Filter reuse (OR 1.69; 95% CI 1.26-2.26; P < .001) and >20 sessions of PEX/patient (OR 1.99; 95% CI 1.27-3.10; P = .002) were independently associated with adverse events; infusion of IV calcium gluconate during PEX was protective (OR 0.26; 95% CI 0.16-0.43; P < .001). Hematological remission was achieved in 96.3% patients after 6 (5-8) PEX sessions; 80.8% and 89.6% patients were dialysis independent by one and 3 months, respectively. CONCLUSIONS: PEX is safe and associated with satisfactory short-term outcomes in children with aHUS. Prolonged PEX and filter-reuse are associated with complications.


Assuntos
Síndrome Hemolítico-Urêmica Atípica/terapia , Filtração/métodos , Troca Plasmática/métodos , Adolescente , Síndrome Hemolítico-Urêmica Atípica/complicações , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Auditoria Médica , Membranas Artificiais , Troca Plasmática/efeitos adversos , Fatores de Risco , Centros de Atenção Terciária , Resultado do Tratamento
8.
G Ital Nefrol ; 36(2)2019 Apr.
Artigo em Italiano | MEDLINE | ID: mdl-30983177

RESUMO

Thrombotic microangiopathies (TMA) are a group of diseases that can complicate pregnancy and threaten the lives of both the mother and the fetus. Several conditions can lead to TMA, including thrombotic thrombocytopenic purpura (TTP), HELLP syndrome and hemolytic uremic syndrome (HUS). We describe the case of a 39-year-old woman who presented a HELLP syndrome in the immediate postpartum period. The patient had acute kidney injury (AKI), increased LDH, unmeasurable haptoglobin levels and hypocomplementemia. Her ADAMTS13 value was normal, thus ruling out TTP. Shiga toxin tests were negative, so HUS associated with E. coli was also ruled out. HELLP syndrome and atypical hemolytic-uremic syndrome (aHUS) remained the most probable diagnosis. In the days following childbirth, the patient's transaminase and bilirubin levels normalized while the anemia persisted, as did the AKI, resulting in the institution of dialysis treatment. A diagnosis of aHUS was made and therapy with eculizumab was started. The patient's blood counts progressively improved, urine output was restored, her indices of renal function also concomitantly improved and dialysis was interrupted. A rash appeared after the third administration of eculizumab and the treatment was suspended. The patient is currently being followed up and has not relapsed. At thirteen months after delivery her renal function is normal as are her platelet counts, LDH, haptoglobin levels and proteinuria. Tests for mutations in the genes that regulate complement activity were negative. We believe that childbirth triggered the HELLP syndrome, which in turn brought about and sustained the HUS. In fact, the patient's liver function improved right after delivery, while her kidney injury and hemolysis persisted, and she also had an excellent response to eculizumab. To our knowledge, no other cases of HELLP syndrome associated with haemolytic uremic syndrome during pregnancy have been reported in literature, nor have cases in which treatment with eculizumab was limited to only three administrations.


Assuntos
Lesão Renal Aguda/complicações , Síndrome Hemolítico-Urêmica Atípica/etiologia , Síndrome HELLP/etiologia , Adulto , Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome Hemolítico-Urêmica Atípica/terapia , Inativadores do Complemento/uso terapêutico , Feminino , Síndrome HELLP/terapia , Humanos , Doenças do Sistema Imunitário/complicações , Período Pós-Parto , Gravidez , Diálise Renal
9.
Iran J Kidney Dis ; 13(2): 134-138, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30988252

RESUMO

While terminal complement blockade with Eculizumab is the first line therapy for atypical HUS (Haemolytic uremic syndrome), lack of its availability and cost limits its use. Plasma exchange becomes a first line modality in the current scenario. However, exposure to large volumes of allogenic plasma and lack of skilled manpower are the limiting factors associated with it. Moreover, there is a subset of patients who fail to respond to plasma exchange. Treatment and follow up records of the children with atypical HUS who did not respond to daily plasma exchange therapy and their course during follow up was reviewed. Three children with positive anti-complement factor H antibody atypical HUS did not respond to daily plasma exchange and were  Rituximab administered after completing five daily treatments. It was seen that these children, initially non-responsive to plasma therapy, attained remission after Rituximab and did not require further plasma exchanges. The remission was sustained in long term with a follow up of 7 years, 4 years and 6 months respectively. Rituximab might be a useful alternative in inducing haematological remission in children with poor or no response to plasma therapy. This abbreviates the duration of plasma exchange, which not only avoids complications due to prolonged plasma therapy but also helps reducing the cost of therapy.


Assuntos
Síndrome Hemolítico-Urêmica Atípica/sangue , Síndrome Hemolítico-Urêmica Atípica/terapia , Imunossupressores/uso terapêutico , Troca Plasmática , Rituximab/uso terapêutico , Autoanticorpos/sangue , Criança , Terapia Combinada , Fator H do Complemento/imunologia , Feminino , Humanos , Masculino , Indução de Remissão
10.
G Ital Nefrol ; 36(1)2019 Feb.
Artigo em Italiano | MEDLINE | ID: mdl-30758152

RESUMO

Atypical hemolytic-uremic syndrome (aHUS) is a rare, potentially lethal (1-4) systemic disorder, capable of affecting both adults and children, causing thrombotic microangiopathy (TMA) (5) that leads to the formation of thrombus within small blood vessels with multiple organ failure. The pathogenesis of the aHUS is part of a sort of chronic and uncontrolled activation of the complement system by genetic mutation of some proteins usually responsible for its self-regulation (6,7). Today, the rapid diagnosis of the disease and the timely start of treatment with eculizumab, improve outcomes of renal failure, stroke and heart attack (8-10). Fabry disease is a rare tesaurismosis, X linked, due to the deficiency of the lysosomal enzyme alpha-galactosidase A (11-13), necessary for the physiological catabolism of glycosphingolipids. Multisystem clinical manifestations lead to a serious degenerative pathology. The diagnostic suspicion based on anamnesis and careful research of the symptoms and then confirmed by the enzymatic dosage of alpha galactosidase or by molecular analysis, allows the early treatment of the patient with enzyme replacement therapy, guaranteeing the resolution and/or slowing down the evolution of the disease, especially in the brain, heart and kidneys. In this report, we describe the clinical case of a patient who is a carrier of both rare diseases.


Assuntos
Síndrome Hemolítico-Urêmica Atípica/complicações , Doença de Fabry/complicações , Adulto , Anticorpos Monoclonais Humanizados/uso terapêutico , Insuficiência da Valva Aórtica/diagnóstico , Síndrome Hemolítico-Urêmica Atípica/genética , Síndrome Hemolítico-Urêmica Atípica/terapia , Terapia de Reposição de Enzimas , Doença de Fabry/diagnóstico , Doença de Fabry/genética , Doença de Fabry/terapia , Feminino , Humanos , Insuficiência da Valva Mitral/diagnóstico , Mutação , alfa-Galactosidase/análise , alfa-Galactosidase/fisiologia
11.
Blood Coagul Fibrinolysis ; 30(2): 68-70, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30676336

RESUMO

: We bring the case of a 38-year-old man who was presented to the emergency department with nausea, fever, and choluria, 4 days after the ingestion of raw oysters. Analytical study revealed thrombocytopenia and acute kidney injury that were associated to a possible thrombotic microangiopathy. Therapeutic plasma exchange was started and resolution of the manifestations was obtained. To identify the cause of the thrombotic microangiopathy a molecular study was performed and a pathogenic variant in the MCP gene, c.287-2A>G (splice acceptor) in heterozygous state with a concomitant presence of both risk haplotypes, MCPggaac and Complement factor H (CFH)-H3 were identified. These findings make the diagnosis of atypical hemolytic-uremic syndrome (aHUS), and despite a relatively benign course with a positive response to plasma exchange without an evolution to renal failure was evident a recurrent profile of aHUS when associated with an infectious trigger.


Assuntos
Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Proteína Cofatora de Membrana/genética , Mutação , Lesão Renal Aguda/etiologia , Adulto , Síndrome Hemolítico-Urêmica Atípica/terapia , Haplótipos , Humanos , Masculino , Fenótipo , Troca Plasmática , Recidiva , Risco , Microangiopatias Trombóticas/etiologia , Microangiopatias Trombóticas/genética
12.
Inflamm Bowel Dis ; 25(4): e27-e28, 2019 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-29931191

RESUMO

Hemolytic-uremic syndrome (HUS) is defined as the triad of nonimmune hemolytic anemia, thrombocytopenia, and acute renal failure, in which the underlying lesions are mediated by systemic thrombotic microangiopathy (TMA). The atypical HUS (aHUS) can be considered a subtype of HUS that is rare in childhood and has a worse prognosis. Recent findings have established that the TMA in aHUS are consequences of the disregulation of the complement activation, leading to endotelial damage mediated by the complement terminal pathway.1, 2 Likewise, previous research suggests an important role for the deregulation of the alternative complement cascade in the pathogenesis of inflammatory bowel disease (IBD).3, 4 We report the case of a patient with ulcerative colitis (UC) who developed aHUS during a flare-up of her chronic disease. This association is extremely infrequent and had been previously reported in only 1 patient.5.


Assuntos
Síndrome Hemolítico-Urêmica Atípica/patologia , Colite Ulcerativa/complicações , Adolescente , Síndrome Hemolítico-Urêmica Atípica/etiologia , Síndrome Hemolítico-Urêmica Atípica/terapia , Feminino , Humanos , Prognóstico
13.
Ther Apher Dial ; 23(1): 4-21, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30294946

RESUMO

Atypical hemolytic uremic syndrome (aHUS), a rare variant of thrombotic microangiopathy, is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and renal impairment. The condition is associated with poor clinical outcomes with high morbidity and mortality. Atypical HUS predominantly affects the kidneys but has the potential to cause multi-organ system dysfunction. This uncommon disorder is caused by a genetic abnormality in the complement alternative pathway resulting in over-activation of the complement system and formation of microvascular thrombi. Abnormalities of the complement pathway may be in the form of mutations in key complement genes or autoantibodies against specific complement factors. We discuss the pathophysiology, clinical manifestations, diagnosis, complications, and management of aHUS. We also review the efficacy and safety of the novel therapeutic agent, eculizumab, in aHUS, pregnancy-associated aHUS, and aHUS in renal transplant patients.


Assuntos
Anticorpos Monoclonais Humanizados/farmacologia , Síndrome Hemolítico-Urêmica Atípica , Via Alternativa do Complemento , Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Síndrome Hemolítico-Urêmica Atípica/etiologia , Síndrome Hemolítico-Urêmica Atípica/fisiopatologia , Síndrome Hemolítico-Urêmica Atípica/terapia , Via Alternativa do Complemento/efeitos dos fármacos , Via Alternativa do Complemento/genética , Via Alternativa do Complemento/imunologia , Gerenciamento Clínico , Humanos , Fatores Imunológicos/farmacologia
14.
J Pediatr Hematol Oncol ; 41(1): e63-e67, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29702545

RESUMO

Atypical hemolytic uremic syndrome (aHUS) is characterized by uncontrolled complement activation leading to thrombotic microangiopathy and severe end-organ damage. The most common trigger for an episode of aHUS in the background of genetic deregulation of the alternative complement pathway is systemic infection. There are only 4 reported cases of aHUS triggered by influenza B thus far. Current accepted therapies for aHUS include plasma exchange and eculizumab. We describe a unique patient with aHUS with a rare membrane cofactor protein mutation triggered by influenza B infection, who achieved complete remission with treatment with high-dose corticosteroids after failure of plasmapheresis.


Assuntos
Corticosteroides/administração & dosagem , Anticorpos Monoclonais Humanizados/administração & dosagem , Síndrome Hemolítico-Urêmica Atípica , Vírus da Influenza B , Influenza Humana , Proteína Cofatora de Membrana/genética , Mutação , Troca Plasmática , Adolescente , Síndrome Hemolítico-Urêmica Atípica/etiologia , Síndrome Hemolítico-Urêmica Atípica/genética , Síndrome Hemolítico-Urêmica Atípica/terapia , Humanos , Influenza Humana/complicações , Influenza Humana/genética , Influenza Humana/terapia , Masculino
15.
Pediatr Nephrol ; 34(3): 533-537, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30560448

RESUMO

BACKGROUND: Hemolytic uremic syndrome (HUS) has been associated with a number of infectious agents. We report here the case of an infant with severe Bordetella pertussis infection who developed HUS. CASE DIAGNOSIS/TREATMENT: A 2-month-old preterm male was admitted for severe Bordetella pertussis infection. Symptoms leading to a diagnosis of hemolytic uremic syndrome (HUS) rapidly appeared: hemolytic anemia, thrombocytopenia, and acute kidney injury. He was treated with 25 days of peritoneal dialysis and received complement-targeting therapy with eculizumab (five injections over 2 months), in addition to blood transfusions, antibiotics, and respiratory support. The outcome was favorable. The genetic workup found a complement factor H gene variant which has been associated with atypical HUS. This variant was located in the C3b-binding site and functional tests revealed that it perturbed the regulatory activity of factor H. CONCLUSION: This case suggests that pertussis is a strong trigger of HUS and that complement investigations are necessary to guide treatment and understand the pathophysiology.


Assuntos
Síndrome Hemolítico-Urêmica Atípica/microbiologia , Bordetella pertussis/imunologia , Complemento C3b/metabolismo , Fator H do Complemento/genética , Coqueluche/complicações , Antibacterianos/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome Hemolítico-Urêmica Atípica/genética , Síndrome Hemolítico-Urêmica Atípica/imunologia , Síndrome Hemolítico-Urêmica Atípica/terapia , Sítios de Ligação/genética , Transfusão de Sangue , Bordetella pertussis/isolamento & purificação , Ativação do Complemento/genética , Ativação do Complemento/imunologia , Complemento C3b/imunologia , Fator H do Complemento/metabolismo , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Diálise Peritoneal , Polimorfismo de Nucleotídeo Único , Coqueluche/imunologia , Coqueluche/microbiologia
16.
Transplant Proc ; 50(10): 3483-3486, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30577225

RESUMO

OBJECTIVE: There are no specific recommendations for therapeutic plasma exchange (TPE) in children after renal transplantation. The purpose of this study was to report the experience with TPE in a pediatric transplant setting. MATERIALS AND METHODS: 59 patients (mean age 12.5 ± 4.5 years) undergoing renal transplantation. Indications for TPE included the recurrence of nephrotic syndrome (NS; n = 30) and atypical hemolytic uremic syndrome (n = 6), chronic antibody-mediated rejection (cAMR; n = 20), sensitization (n = 2), and immune thrombocytopenia (n = 1). The single-filtration TPE was performed in all cases. In 74.7% of patients, fresh frozen plasma was used as a replacement fluid. In 25.3% of patients, 4% albumin solution was used as a replacement fluid. Criteria for TPE efficacy included a decrease of proteinuria and normalization of renal function in NS; a normalization of platelet count, C3, and hemoglobin concentration in aHUS; improvement in renal function; and reduction of donor-specific antibodies in cAMR; and removal of antiplatelet antibodies in immune thrombocytopenia. RESULTS: Efficacy results for patients with NS: 59.3% achieved remission, 25.9% achieved partial remission, and 14.8% achieved no remission, respectively. For patients with atypical hemolytic uremic syndrome there was remission in 66.6% and no remission in 33.4%. For patients with cAMR there was remission in 75% and no remission in 25%. Antiplatelet antibodies disappeared after TPE in 1 patient. In 9% of TPE procedures, minor complications were noted. All patients were on posttransplant maintenance immunosuppression and several children received additional treatment (intravenous immunoglobulin therapy or rituximab) during TPE therapy. CONCLUSION: TPE therapy (combined with immunosuppression) was an effective tool in most pediatric cases after renal transplantation with low incidence of minor adverse events.


Assuntos
Imunossupressão/métodos , Transplante de Rim/efeitos adversos , Troca Plasmática/métodos , Complicações Pós-Operatórias/terapia , Adolescente , Síndrome Hemolítico-Urêmica Atípica/etiologia , Síndrome Hemolítico-Urêmica Atípica/terapia , Criança , Feminino , Rejeição de Enxerto/terapia , Humanos , Masculino , Síndrome Nefrótica/etiologia , Síndrome Nefrótica/terapia , Púrpura Trombocitopênica Idiopática/etiologia , Recidiva , Estudos Retrospectivos , Resultado do Tratamento
19.
Am J Nephrol ; 48(3): 225-233, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30205388

RESUMO

BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is a rare disease associated with congenital or acquired genetic abnormalities that result in uncontrolled complement activation, leading to thrombotic microangiopathy and kidney failure. Until recently, the only treatment was plasma exchange or plasma infusion (PE/PI), but 60% of patients died or had permanent kidney damage despite treatment. Eculizumab, a complement inhibitor, has shown promising results in aHUS. However, data are mainly extracted from case reports or studies of heterogeneous cohorts, and no direct comparison with PE/PI is available. METHODS: An observational retrospective study of adult, dialysis-dependent aHUS patients with acute kidney injury (AKI) who were treated with either PE/PI alone or with second-line eculizumab in our center. We compared the effect of PE/PI and eculizumab on kidney function, hypertension, proteinuria, hematologic values, relapse, and death. RESULTS: Thirty-one patients were included (females, 18; sporadic aHUS, 29; mean age, 46 ± 20 years). Twenty-six patients were treated with PE/PI alone, and 5 were deemed to be plasma-resistant and received eculizumab after stopping PE/PI. Among patients receiving eculizumab, 80% attained complete recovery of kidney function, 100% stopped dialysis, 20% had decreased proteinuria, and no patient relapsed (vs. 38.5, 50, 15.4, and 11.5%, respectively, of patients receiving only PE/PI). At 1-year of follow-up, no deaths had occurred in either group. CONCLUSION: Eculizumab shows greater efficacy than PE/PI alone for the treatment of adult aHUS patients with AKI. Prospective studies and meta-analyses are warranted to confirm our findings and set guidelines for treatment, monitoring, and maintenance.


Assuntos
Lesão Renal Aguda/terapia , Anticorpos Monoclonais Humanizados/administração & dosagem , Síndrome Hemolítico-Urêmica Atípica/complicações , Inativadores do Complemento/administração & dosagem , Troca Plasmática , Lesão Renal Aguda/etiologia , Lesão Renal Aguda/fisiopatologia , Adulto , Idoso , Síndrome Hemolítico-Urêmica Atípica/terapia , Feminino , Seguimentos , Humanos , Rim/efeitos dos fármacos , Rim/fisiologia , Masculino , Pessoa de Meia-Idade , Diálise Renal , Estudos Retrospectivos , Prevenção Secundária/métodos , Resultado do Tratamento
20.
Rev Med Chil ; 146(6): 770-779, 2018 Jun.
Artigo em Espanhol | MEDLINE | ID: mdl-30148909

RESUMO

Atypical hemolytic uremic syndrome (aHUS) is a rare thrombotic microangiopathy, characterized by microangiopathic hemolytic anemia, thrombocytopenia and renal involvement. It causes end stage renal disease requiring dialysis in most affected patients. It mainly affects young adults (contrary to what was thought years ago). When aHUS is primary, the cause is a genetic mutation in the alternative complement pathway. Instead, secondary aHUS is caused by external factors that trigger the disease by themselves or in combination with a genetic vulnerability. The type of mutation determines the severity of the disease, prognosis, response to therapy and renal transplantation. Advances in the understanding of renal diseases associated with complement defects and the development of specific biologic therapies changed the course of this disease. Eculizumab is internationally approved for the treatment of primary aHUS. Its inhibitory action on the complement cascade leads to hematologic remission and restoration of renal function. We present a review of aHUS detailing its etiology, pathogenesis, clinical presentation, diagnosis and treatment.


Assuntos
Síndrome Hemolítico-Urêmica Atípica/etiologia , Síndrome Hemolítico-Urêmica Atípica/terapia , Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Humanos , Transplante de Rim , Mutação
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