Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 130
Filtrar
1.
J Pak Med Assoc ; 71(5): 1496-1498, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34091644

RESUMO

Atypical Haemolytic Uraemic Syndrome (aHUS) is considered an uncommon pathology that usually affects young adults and causes acute kidney injury which can further lead to End Stage Renal Disease (ESRD). Here we present the case of a previously healthy young boy who was diagnosed as a case of atypical HUS on renal biopsy in Sheikh Zayed Hospital Lahore. His C3 was low, while ANA and C-ANCA P-ANCA were in normal range; multiple sessions of plasmapheresis were conducted, whereas IV Methylprednisolone was also given during both admissions (the patient had to be readmitted six months later after having been discharged on improvement). After that, his GFR improved along with other laboratory parameters. Rituximab was also offered but the family refused due to affordability issue.


Assuntos
Injúria Renal Aguda , Síndrome Hemolítico-Urêmica Atípica , Falência Renal Crônica , Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Síndrome Hemolítico-Urêmica Atípica/terapia , Humanos , Masculino , Nefrectomia , Plasmaferese
2.
Am J Case Rep ; 22: e929616, 2021 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-33678802

RESUMO

BACKGROUND Atypical hemolytic uremic syndrome (aHUS) is a set of heterogenous disorders of thrombotic microangiopathy defined by thrombocytopenia, hemolytic anemia, and acute renal failure that is not mediated by shiga toxin. Factor Eight Inhibitor Bypassing Activity (FEIBA) is a concentrate of inactivated and activated coagulation factors that is approved for use to establish hemostasis in patients with hemophilia or acquired factor inhibitors. However, it has recently been used off-label as an anticoagulant reversal therapy among the general population. Additionally, post-market surveillance has shown increased thromboembolic adverse events, whereas micro-thrombotic complications are rarely described. CASE REPORT A 58-year-old man with a history of hypertension and a single deep vein thrombosis on warfarin presented with right upper-quadrant tenderness extending to the right flank. He was found to have a hepatic hematoma and was given activated prothrombin complex concentrate (aPCC) of 14 150 units of anti-inhibitor coagulant complex at 100 units per kilogram due to concern for active hemorrhage. Subsequently, he developed anemia, thrombocytopenia, and renal failure consistent with atypical HUS. He was treated with hemodialysis, corticosteroids, plasma exchange, and 4 weekly doses of the anti-C5 antibody eculizumab. The patient subsequently recovered, demonstrating improved hemoglobin, creatinine, and platelets. He eventually achieved hemodialysis independence. Follow-up showed no evidence of recurrent atypical HUS and the patient has not needed maintenance eculizumab. CONCLUSIONS Herein, we report the first case of aHUS associated with administration of a single large dose of aPCC for anticoagulation reversal. We postulate a potential mechanism for FEIBA-induced aHUS and report the efficacy of a short trial of eculizumab.


Assuntos
Síndrome Hemolítico-Urêmica Atípica , Anticorpos Monoclonais Humanizados/efeitos adversos , Síndrome Hemolítico-Urêmica Atípica/terapia , Fatores de Coagulação Sanguínea , Humanos , Masculino , Pessoa de Meia-Idade , Troca Plasmática
3.
Clin Nephrol ; 95(3): 156-160, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33210998

RESUMO

INTRODUCTION: Atypical hemolytic uremic syndrome (aHUS) is characterized by hemolytic anemia, thrombocytopenia, and acute kidney injury. Uncontrolled activation of the complement system induced by single or combined complement gene mutations is one of the mechanisms leading to the pathogenesis of aHUS. CASE PRESENTATION: We report a case of a 26-year-old female with a C3 heterozygous gene mutation (p.Asn153Asn). The patient was found to have low complement H factor (CFH) but normal levels of anti-CFH autoantibody. She was treated primarily with plasma exchange and plasma infusion. The patient did not relapse during a 1-year follow-up. CONCLUSION: This is the first case of a novel C3 mutation (p.Asn153Asn) in a patient with aHUS. Further studies are needed to confirm the association between this mutation and the CFH level.


Assuntos
Síndrome Hemolítico-Urêmica Atípica , Complemento C3/genética , Adulto , Síndrome Hemolítico-Urêmica Atípica/sangue , Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Síndrome Hemolítico-Urêmica Atípica/terapia , Autoanticorpos/sangue , Fator H do Complemento/análise , Fator H do Complemento/imunologia , Feminino , Humanos , Mutação/genética , Troca Plasmática
5.
BMC Pregnancy Childbirth ; 20(1): 495, 2020 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-32854648

RESUMO

BACKGROUND: Thrombotic microangiopathy is associated with HELLP syndrome, thrombotic thrombocytopenic purpura, or atypical hemolytic uremic syndrome (aHUS) during pregnancy. Standard laboratory and physical examinations can help distinguish between these three diseases promptly and guide their management. This is critical because their managements and prognoses differ considerably. The ADAMTS13 test, complement tests, and biopsies can help ascertain the diagnosis; however, they take time, and are not widely available. In this case report, we present a case that highlights the diagnostic and therapeutic dilemmas associated with the aforementioned diseases. CASE PRESENTATION: A 31-year old P3G3 patient presented at 38 weeks with high blood pressure, bilateral pitting edema, and a low fetal heart rate. A cesarean section was performed to extract the fetus. On postoperative day 2, the suites were marked by anemia, low platelet count, acute kidney injury, declining liver function, and the presence of schistocytes on the peripheral thin smear. The patient was lucid, coherent, and presented no neurological deficits. The ADAMTS13 test and anti-complement therapy were not readily available, so the team made a presumptive diagnosis of aHUS based on the history, clinical presentation, and standard laboratory results. Due to a lack of anticomplement therapy, the patient was prescribed four sessions of hemodialysis. The renal function and platelet count gradually increased, and the patient was discharged on postoperative day 18. The patient was followed for over a year and did not present relapses of thrombocytopenia or microangiopathic hemolytic anemia. CONCLUSIONS: The prompt diagnosis and management of aHUS lead to favorable outcomes. Healthcare providers should be able to rapidly differentiate between pregnancy-associated thrombotic microangiopathies and prescribe appropriate management. Here, we highlighted the challenges of diagnosing and managing postpartum associated aHUS in a low-resource setting.


Assuntos
Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Transtornos Puerperais/diagnóstico , Adulto , Síndrome Hemolítico-Urêmica Atípica/terapia , Congo , Diagnóstico Diferencial , Feminino , Humanos , Gravidez , Transtornos Puerperais/terapia
6.
Eur J Pediatr ; 179(11): 1739-1750, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32424742

RESUMO

Atypical haemolytic uraemic syndrome is an ultra-rare, life-threatening disease. Causative variants in genes that encode complement factors can be identified in 40-70% of cases. We performed genetic analysis of 21 Czech children with atypical haemolytic uraemic syndrome. Genetic or acquired predisposition to the disease was identified in the majority of our patients: CFHR1 and CFHR3 deletions in 14/21 (67%; 13 of them were positive for anti-complement factor H antibodies), variants in complement genes or DGKE in 13/21 (62%). Multiple genetic findings were identified in eight patients (38%). The incidence of atypical haemolytic uraemic syndrome in the Czech paediatric population was estimated to be 0.092 (CI 0.053-0.131) cases per million inhabitants and 0.92 (CI 0.53-1.32) cases per 100,000 births for the entire reporting period. Ten patients were initially treated with plasma exchange and eight with eculizumab or with a combination of eculizumab and plasma exchange. At the last follow-up, 20 patients were alive and one patient had end-stage renal disease.Conclusion: The incidence of atypical haemolytic uraemic syndrome in the Czech paediatric population corresponds to the reported incidence in Europe. We detected the unusually high rate of CFHR1/CFHR3 deletions associated with anti-complement factor H antibodies in Czech paediatric patients. Treatment by eculizumab led to superior outcomes and prevention of the disease relapses compared with plasma exchange therapy. Our results may help to understand the polygenic nature of atypical haemolytic uraemic syndrome as a disease that results from a combination of various risk factors. What is Known: • Atypical haemolytic uraemic syndrome (aHUS) is considered a polygenic and multifactorial disease. Genetic predisposition to aHUS is identified in 40-70% of children. • Anti-complement factor H antibodies are usually found in 6-25% of affected children. What is New: • Potentially causative genetic or acquired factors were confirmed in the majority of patients. The prevailing finding was the unusually high rate of CFHR1/CFHR3 deletions associated with anti-complement factor H antibodies (62% of patients). • The incidence of aHUS in Czech children is 0.092 (CI 0.053-0.131) cases per million inhabitants and 0.92 (CI 0.53-1.32) cases per 100,000 births for the entire reporting period.


Assuntos
Síndrome Hemolítico-Urêmica Atípica , Síndrome Hemolítico-Urêmica Atípica/epidemiologia , Síndrome Hemolítico-Urêmica Atípica/genética , Síndrome Hemolítico-Urêmica Atípica/terapia , Criança , República Tcheca/epidemiologia , Europa (Continente) , Humanos , Troca Plasmática , Fatores de Risco
7.
Crit Care Clin ; 36(2): 333-356, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32172817

RESUMO

Hemolytic uremic syndrome is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. Disseminated intravascular coagulation, thrombotic thrombocytopenic purpura, and hemolytic uremic syndrome have a similar clinical presentation. Diagnostic needs to be prompt to decrease mortality, because identifying the different disorders can help to tailor specific, effective therapies. However, diagnosis is challenging and morbidity and mortality remain high, especially in the critically ill population. Development of clinical prediction scores and rapid diagnostic tests for hemolytic uremic syndrome based on mechanistic knowledge are needed to facilitate early diagnosis and assign timely specific treatments to patients with hemolytic uremic syndrome variants.


Assuntos
Estado Terminal , Síndrome Hemolítico-Urêmica/diagnóstico , Síndrome Hemolítico-Urêmica/etiologia , Algoritmos , Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Síndrome Hemolítico-Urêmica Atípica/etiologia , Síndrome Hemolítico-Urêmica Atípica/genética , Síndrome Hemolítico-Urêmica Atípica/terapia , Diagnóstico Diferencial , Diagnóstico Precoce , Síndrome Hemolítico-Urêmica/genética , Síndrome Hemolítico-Urêmica/terapia , Humanos , Prognóstico , Fatores de Risco , Toxina Shiga/toxicidade
8.
Korean J Intern Med ; 35(1): 25-40, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31935318

RESUMO

Thrombotic microangiopathy (TMA) is defined by specific clinical characteristics, including microangiopathic hemolytic anemia, thrombocytopenia, and pathologic evidence of endothelial cell damage, as well as the resulting ischemic end-organ injuries. A variety of clinical scenarios have features of TMA, including infection, pregnancy, malignancy, autoimmune disease, and medications. These overlapping manifestations hamper differential diagnosis of the underlying pathogenesis, despite recent advances in understanding the mechanisms of several types of TMA syndrome. Atypical hemolytic uremic syndrome (aHUS) is caused by a genetic or acquired defect in regulation of the alternative complement pathway. It is important to consider the possibility of aHUS in all patients who exhibit TMA with triggering conditions because of the incomplete genetic penetrance of aHUS. Therapeutic strategies for aHUS are based on functional restoration of the complement system. Eculizumab, a monoclonal antibody against the terminal complement component 5 inhibitor, yields good outcomes that include prevention of organ damage and premature death. However, there remain unresolved challenges in terms of treatment duration, cost, and infectious complications. A consensus regarding diagnosis and management of TMA syndrome would enhance understanding of the disease and enable treatment decision-making.


Assuntos
Síndrome Hemolítico-Urêmica Atípica , Microangiopatias Trombóticas , Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Síndrome Hemolítico-Urêmica Atípica/terapia , Inativadores do Complemento/uso terapêutico , Consenso , Diagnóstico Diferencial , Feminino , Humanos , Gravidez , Microangiopatias Trombóticas/diagnóstico
9.
Nephrology (Carlton) ; 25(7): 518-521, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31900968

RESUMO

Atypical haemolytic uraemic syndrome (aHUS) is a severe, life-threatening condition that requires early recognition and urgent treatment. In aHUS rare genetic variants in CFH, CFI, CD46, C3 and CFB predispose to complement over activation. This case describes a case of aHUS in which there was a strong temporal association between disease onset and the use of smoked cocaine. The patient was found to have a rare genetic variant in the CFI gene which may have been unmasked by first-time exposure to cocaine. The patient stabilized and improved with early administration of eculizumab, supporting the notion of an underlying immunological pathogenesis and the importance of early intervention.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Síndrome Hemolítico-Urêmica Atípica , Fumar Cocaína , Fator I do Complemento/genética , Insuficiência Renal , Trombocitopenia , Síndrome Hemolítico-Urêmica Atípica/genética , Síndrome Hemolítico-Urêmica Atípica/fisiopatologia , Síndrome Hemolítico-Urêmica Atípica/terapia , Biópsia/métodos , Fumar Cocaína/efeitos adversos , Fumar Cocaína/prevenção & controle , Humanos , Rim/patologia , Rim/fisiopatologia , Testes de Função Renal/métodos , Masculino , Pessoa de Meia-Idade , Mutação , Prognóstico , Diálise Renal/métodos , Insuficiência Renal/diagnóstico , Insuficiência Renal/terapia , Trombocitopenia/diagnóstico , Trombocitopenia/etiologia , Trombocitopenia/terapia , Microangiopatias Trombóticas/etiologia , Microangiopatias Trombóticas/patologia , Resultado do Tratamento
10.
J Med Case Rep ; 14(1): 11, 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31928535

RESUMO

BACKGROUND: Thrombotic microangiopathy is a pathological condition comprised of microvascular thrombosis involving any organ of the body leading to thrombocytopenia, Coombs-negative hemolytic anemia, and end-organ damage. The most common forms of thrombotic microangiopathies are Shiga toxin-producing Escherichia coli-mediated hemolytic uremic syndrome, thrombotic thrombocytopenic purpura, and atypical hemolytic uremic syndrome. The atypical hemolytic uremic syndrome occurs due to genetic and acquired mutations in complement regulatory factors and to complement activation factors in the immune system, mainly the alternative pathway. Clinical manifestations and outcomes differ with the prevalent mutations of the patient. Currently, available treatment modalities are therapeutic plasma exchange and a monoclonal antibody against C5, eculizumab. We report a case of a Sri Lankan girl diagnosed with atypical hemolytic uremic syndrome complicated with septicemia, hemolytic anemia, acute kidney injury, pulmonary hemorrhage with respiratory failure, and hypertension who had a complete remission following long-term (30 months) therapeutic plasma exchange. CASE PRESENTATION: A 15-year-old Sri Lankan girl was transferred from a local hospital with the features of septicemia and acute kidney injury for specialized management. She had high blood pressure (180/100 mmHg) on admission. She underwent appendicectomy based on suspicion of acute appendicitis as the cause of sepsis. Following surgery, her condition deteriorated, and intensive care unit management was warranted because she developed pulmonary hemorrhages and respiratory failure requiring mechanical ventilation and renal replacement therapy in the form of hemodialysis. Her blood investigations showed microangiopathic hemolytic anemia, thrombocytopenia, elevated lactate dehydrogenase, and reduced human complement C3 levels, together with a normal coagulation profile. She was diagnosed with atypical hemolytic uremic syndrome and was initiated on therapeutic plasma exchange and other supportive therapy, including corticosteroids. Following a lengthy course of plasma exchange, complete recovery was achieved. CONCLUSION: The atypical hemolytic uremic syndrome is a rare disease entity requiring a high index of suspicion to diagnose. It is a diagnosis of exclusion. Early diagnosis with prompt treatment will render a better outcome. The atypical hemolytic uremic syndrome needs to be considered in all patients with thrombotic microangiopathy.


Assuntos
Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Síndrome Hemolítico-Urêmica Atípica/terapia , Troca Plasmática , Injúria Renal Aguda/etiologia , Adolescente , Corticosteroides/uso terapêutico , Anemia Hemolítica/etiologia , Síndrome Hemolítico-Urêmica Atípica/complicações , Feminino , Hemorragia/etiologia , Humanos , Hipertensão/etiologia , Diálise Renal , Respiração Artificial , Insuficiência Respiratória/etiologia , Sepse/etiologia , Resultado do Tratamento
11.
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
12.
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 , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade
13.
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
15.
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 , Injúria Renal Aguda/classificação , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/terapia , Adulto , Anemia Hemolítica/etiologia , Anemia Hemolítica/terapia , Cesárea , Feminino , Humanos , Troca Plasmática , Gravidez , Recidiva
16.
Kidney Int ; 96(4): 995-1004, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31420192

RESUMO

Malignant hypertension is listed among the causes of secondary thrombotic microangiopathy, but pathogenic mutations in complement genes have been reported in patients with hypertension-induced thrombotic microangiopathy. Here we investigated the frequency and severity of hypertension in 55 patients with primary atypical hemolytic uremic syndrome (aHUS). A genetic analysis was performed in all patients, and funduscopic examination was performed in all the patients with Grades 2 and 3 hypertension. A cohort of 110 patients with malignant hypertension caused by diseases other than aHUS served as control. Thirty-six patients with aHUS presented Grade 2 or Grade 3 hypertension and funduscopic examination showed malignant hypertension in 19. Genetic abnormalities in complement were found in 19 patients (37% among patients with malignant hypertension). Plasmapheresis was performed in 46 patients and 26 received eculizumab. Renal and hematological responses were significantly lower after plasmapheresis (24%) than after eculizumab (81%). Renal survival was significantly higher in patients treated with eculizumab (85% at one, three and five years) compared to patients who did not receive this treatment (54%, 46% and 41%), respectively. Response to eculizumab was independent of hypertension severity and the presence of complement genetic abnormalities. Among patients with malignant hypertension caused by other diseases the prevalence of thrombotic microangiopathy was very low (5%). Thus, severe and malignant hypertension are common among patients with aHUS and eculizumab treatment leads to a higher renal survival when compared to plasmapheresis. However, thrombotic microangiopathy is uncommon among patients presenting with malignant hypertension caused by diseases other than aHUS.


Assuntos
Síndrome Hemolítico-Urêmica Atípica/complicações , Proteínas do Sistema Complemento/genética , Hipertensão Maligna/epidemiologia , Índice de Gravidade de Doença , Adulto , Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome Hemolítico-Urêmica Atípica/genética , Síndrome Hemolítico-Urêmica Atípica/terapia , Inativadores do Complemento/uso terapêutico , Feminino , Humanos , Hipertensão Maligna/diagnóstico , Hipertensão Maligna/genética , Hipertensão Maligna/terapia , Incidência , Masculino , Pessoa de Meia-Idade , Plasmaferese , Estudos Retrospectivos , Adulto Jovem
17.
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
18.
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
19.
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
20.
Front Immunol ; 10: 1282, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31231391

RESUMO

Background: Atypical hemolytic uremic syndrome (aHUS), an important cause of acute kidney injury (AKI), is characterized by dysregulation of the alternative complement pathway. Autoantibodies to factor H (FH), a chief regulator of this pathway, account for a distinct subgroup. While high anti-FH titers predict relapse, they do not correlate well with disease activity and their functional characterization is required. Methods: Of 781 patients <18-year-old of aHUS in the nationwide database from 2007 to 2018, 436 (55.8%) had anti-FH antibodies. Clinical features and outcome of patients managed in the last 6-year (n = 317) were compared to before (n = 119). In plasma samples of 44 patients, levels of serial circulating FH immune complexes (CIC), free FH, soluble terminal complement complex (sC5b-9), sheep red blood cell (SRBC) lysis and epitope specificity (n = 8) were examined. Functional renal reserve, ambulatory hypertension, left ventricular hypertrophy (LVH), and proteinuria were evaluated in a subset. Results: Patients presented with markedly elevated anti-FH titers (10,633.2 ± 998.5 AU/ml). Management varied by center, comprising plasma exchange (PEX; 77.5%) and immunosuppression (73.9%). Patients managed in the last 6-year showed better renal survival at mean 28.5 ± 27.3 months (log rank P = 0.022). Mean anti-FH titers stayed 700-1,164 AU/ml during prolonged follow-up, correlating with CIC. Patients with relapse had lower free-FH during remission [Generalized estimating equations (GEE), P = 0.001]; anti-FH levels ≥1,330 AU/ml and free FH ≤440 mg/l predicted relapse (hazards ratio, HR 6.3; P = 0.018). Epitope specificity was similar during onset, remission and relapse. Antibody titer ≥8,000 AU/ml (HR 2.23; P = 0.024), time to PEX ≥14 days (HR 2.09; P = 0.071) and PEX for <14 days (HR 2.60; P = 0.017) predicted adverse renal outcomes. Combined PEX and immunosuppression improved long-term outcomes (HR 0.37; P = 0.026); maintenance therapy reduced risk of relapses (HR 0.11; P < 0.001). At 4.4±2.5 year, median renal reserve was 15.9%; severe ambulatory, masked and pre-hypertension were found in 38, 30, and 18%, respectively. Proteinuria and LVH occurred in 58 and 28% patients, respectively. Conclusion: Prompt recognition and therapy with PEX and immunosuppression, is associated with satisfactory outcomes. Free-FH predicts early relapses in patients with high anti-FH titers. A significant proportion of impaired functional reserve, ambulatory hypertension, proteinuria and LVH highlight the need for vigilant long-term follow-up.


Assuntos
Síndrome Hemolítico-Urêmica Atípica/imunologia , Adolescente , Síndrome Hemolítico-Urêmica Atípica/patologia , Síndrome Hemolítico-Urêmica Atípica/terapia , Autoanticorpos/imunologia , Autoantígenos/imunologia , Criança , Pré-Escolar , Fator H do Complemento/imunologia , Bases de Dados Factuais , Feminino , Humanos , Imunossupressores/uso terapêutico , Lactente , Masculino
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...