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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
3.
Orphanet J Rare Dis ; 16(1): 240, 2021 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-34034793

RESUMO

BACKGROUND: Hemolytic uremic syndrome (HUS) is a rare condition which diagnosed with the triad of thrombocytopenia, microangiopathic hemolytic anemia, and acute renal injury. There is a high requirement for research to discover treatments. HUS registries can be used as an important information infrastructure. In this study, we identified and compared the different features of HUS registries to present a guide for the development and implementation of HUS registries. RESULTS: The purposes of registries were classified as clinical (9 registries), research (7 registries), and epidemiological (5 registries), and only 3 registries pursued all three types of purposes. The data set included demographic data, medical and family history, para-clinical and diagnostic measures, treatment and pharmacological data, complications, and outcomes. The assessment strategies of data quality included monthly evaluation and data audit, the participation of physicians to collect data, editing and correcting data errors, increasing the rate of data completion, following guidelines and data quality training, using specific data quality indicators, and real-time evaluation of data at the time of data entry. 8 registries include atypical HUS patients, and 7 registries include all patients regardless of age. Only two registries focused on children. 4 registries apply prospective and 4 applied both prospective, and retrospective data collection. Finally, specialized hospitals were the main data source for these registries. CONCLUSION: Based on the findings, we suggested a learning framework for developing and implementing an HUS registry. This framework includes lessons learned and suggestions for HUS registry purposes, minimum data set, data quality assurance, data collection methods, inclusion and exclusion criteria as well as data sources. This framework can help researchers develop HUS registries.


Assuntos
Síndrome Hemolítico-Urêmica Atípica , Púrpura Trombocitopênica Trombótica , Criança , Humanos , Estudos Prospectivos , Sistema de Registros , Estudos Retrospectivos
4.
Methods Mol Biol ; 2227: 1-20, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33847926

RESUMO

The complement cascade is an evolutionary ancient innate immune defense system, playing a major role in the defense against infections. Its function in maintaining host homeostasis on activated cells has been emphasized by the crucial role of its overactivation in ever growing number of diseases, such as atypical hemolytic uremic syndrome (aHUS), autoimmune diseases as systemic lupus erythematosus (SLE), C3 glomerulopathies (C3GN), age-related macular degeneration (AMD), graft rejection, Alzheimer disease, and cancer, to name just a few. The last decade of research on complement has extended its implication in many pathological processes, offering new insights to potential therapeutic targets and asserting the necessity of reliable, sensitive, specific, accurate, and reproducible biomarkers to decipher complement role in pathology. We need to evaluate accurately which pathway or role should be targeted pharmacologically, and optimize treatment efficacy versus toxicity. This chapter is an introduction to the role of complement in human diseases and the use of complement-related biomarkers in the clinical practice. It is a part of a book intending to give reliable and standardized methods to evaluate complement according to nowadays needs and knowledge.


Assuntos
Proteínas do Sistema Complemento/análise , Testes Diagnósticos de Rotina/métodos , Padrões de Prática Médica , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/imunologia , Doença de Alzheimer/metabolismo , Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Síndrome Hemolítico-Urêmica Atípica/imunologia , Síndrome Hemolítico-Urêmica Atípica/metabolismo , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/imunologia , Doenças Autoimunes/metabolismo , Ativação do Complemento/fisiologia , Proteínas do Sistema Complemento/metabolismo , Desenvolvimento de Medicamentos , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/metabolismo , Humanos , Nefropatias/diagnóstico , Nefropatias/imunologia , Nefropatias/metabolismo , Degeneração Macular/diagnóstico , Degeneração Macular/imunologia , Degeneração Macular/metabolismo , Neoplasias/diagnóstico , Neoplasias/imunologia , Neoplasias/metabolismo
5.
Methods Mol Biol ; 2227: 69-81, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33847932

RESUMO

Impairment of the complement regulatory protein Factor H (FH) is implicated in the physiopathological mechanisms of different diseases like atypical hemolytic and uremic syndrome and C3 glomerulopathies. It may be due to genetic abnormalities or acquired with the development of autoantibodies. FH has several ligands; therefore, the exploration of its functions requires to perform different tests. Among them, two hemolytic tests are very useful because they give specific and complementary information about FH functions. The first one is dedicated to explore the FH capacity to dissociate the alternative pathway C3 convertase, whereas the second one is designed to explore the capacity of FH to bind cell surfaces and to protect them from complement attack. This chapter describes the procedures to perform these two hemolytic tests, exploring in a complementary way the FH functionality.


Assuntos
Fator H do Complemento/análise , Fator H do Complemento/fisiologia , Ensaio de Atividade Hemolítica de Complemento/métodos , Animais , Síndrome Hemolítico-Urêmica Atípica/sangue , Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Síndrome Hemolítico-Urêmica Atípica/imunologia , Complemento C3b/análise , Complemento C3b/metabolismo , Citaferese/métodos , Eritrócitos/citologia , Eritrócitos/metabolismo , Humanos , Nefropatias/sangue , Nefropatias/diagnóstico , Nefropatias/imunologia , Ratos , Ovinos
6.
Methods Mol Biol ; 2227: 83-96, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33847933

RESUMO

The complement system is a key part of innate immunity. However, if the system becomes dysregulated, damage to healthy host cells can occur, especially to the glomerular cells of the kidney. The convertases of the alternative pathway of the complement system play a crucial role in complement activation. In healthy conditions, their activity is strictly regulated. In patients with diseases caused by complement alternative pathway dysregulation, such as C3 glomerulopathy and atypical hemolytic uremic syndrome, factors can be present in the blood that disturb this delicate balance, leading to convertase overactivity. Such factors include C3 nephritic factors, which are autoantibodies against the C3 convertase that prolong its activity, or genetic variants resulting in a stabilized convertase complex. This chapter describes a method in which the activity and stability of the alternative pathway convertases can be measured to detect aberrant serum factors causing convertase overactivity.


Assuntos
Convertases de Complemento C3-C5/metabolismo , Ensaio de Atividade Hemolítica de Complemento/métodos , Via Alternativa do Complemento , Animais , Síndrome Hemolítico-Urêmica Atípica/sangue , Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Síndrome Hemolítico-Urêmica Atípica/imunologia , Ativação do Complemento , Complemento C3/imunologia , Fator Nefrítico do Complemento 3/análise , Fator Nefrítico do Complemento 3/imunologia , Convertases de Complemento C3-C5/análise , Via Alternativa do Complemento/imunologia , Glomerulonefrite/sangue , Glomerulonefrite/diagnóstico , Glomerulonefrite/imunologia , Cobaias , Humanos , Coelhos
7.
Methods Mol Biol ; 2227: 97-105, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33847934

RESUMO

The three pathways of the complement system converge toward the cleavage of the central complement component C3 into its activated fragments, with C3b being able to bind covalently to the activating surface. The endothelial cells are among the major targets for complement attack in pathological conditions, as the atypical hemolytic uremic syndrome. Therefore, study of complement C3 deposition on endothelial cells by flow cytometry is a sensitive test to measure complement activation. This test can be used as a research or clinical tool to test complement activation induced by patients' sera or to test the functional consequences of newly discovered complement mutations as well as different triggers of endothelial cells injury.


Assuntos
Complemento C3/metabolismo , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Citometria de Fluxo/métodos , Síndrome Hemolítico-Urêmica Atípica/sangue , Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Síndrome Hemolítico-Urêmica Atípica/imunologia , Células Cultivadas , Ativação do Complemento/fisiologia , Células Endoteliais/patologia , Humanos , Ligação Proteica
8.
Medicine (Baltimore) ; 100(11): e25069, 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33725982

RESUMO

RATIONALE: Atypical hemolytic uremic syndrome (aHUS) is an uncommon and serious disease that manifests hemolytic anemia, thrombocytopenia, and acute kidney injury. Genetic complement abnormalities have been shown to be responsible. Compared with the aHUS caused by other mutated genes, aHUS secondary to CFB mutation in adults is extremely rare. We report an adult with CFB mutation developing aHUS. PATIENT CONCERNS: A 56-year-old man was admitted for 4-day history of nausea and fatigue, anuria for 2 days, and unconsciousness for 10 hours. DIAGNOSES: The patient presented with life-threatening anemia, thrombocytopenia, acute kidney injury, and nervous system abnormalities. The patient had schistocytes on the peripheral blood smear, increased lactate dehydrogenase (LDH), and plasma-free hemoglobin levels. The patient was later found to harbor a pathogenic variant in the CFB gene (C.1598A>G), and was diagnosed with aHUS and acute kidney injury. INTERVENTION: The patient was treated by plasmapheresis, continuous renal replacement therapy, blood transfusion, and anti-infective and antihypertensive treatment. OUTCOMES: After the treatment, the patient's consciousness returned to normal, and the hemoglobin, platelet, and serum creatinine recovered. The disease activity remained quiescent during the follow-up. LESSONS: A rare heterozygous variant c.1598A>G p.Lys 533Arg in the CFB gene, which was associated with adult-onset aHUS, was described and successfully treated. This case can help in understanding the early diagnosis and effective therapies of this rare disease.


Assuntos
Síndrome Hemolítico-Urêmica Atípica/genética , Fator B do Complemento/genética , Necrose Tubular Aguda/genética , Mutação/genética , Humanos , Masculino , Pessoa de Meia-Idade
9.
Blood Adv ; 5(5): 1504-1512, 2021 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-33683339

RESUMO

Terminal complement inhibition is the standard of care for atypical hemolytic uremic syndrome (aHUS). The optimal duration of complement inhibition is unknown, although indefinite therapy is common. Here, we present the outcomes of a physician-directed eculizumab discontinuation and monitoring protocol in a prospective cohort of 31 patients that started eculizumab for acute aHUS (and without a history of renal transplant). Twenty-five (80.6%) discontinued eculizumab therapy after a median duration on therapy of 2.37 (interquartile range: 1.06, 9.70) months. Eighteen patients discontinued per protocol and 7 because of nonadherence. Of these, 5 (20%) relapsed; however, relapse rate was higher in the case of nonadherence (42.8%) vs clinician-directed discontinuation and monitoring (11.1%). Four of 5 patients who relapsed were successfully retreated without a decline in renal function. One patient died because of recurrent aHUS and hypertensive emergency in the setting of nonadherence. Nonadherence to therapy (odds ratio, 8.25; 95% confidence interval, 1.02-66.19; P = .047) was associated with relapse, whereas the presence of complement gene variants (odds ratio, 1.39; 95% confidence interval, 0.39-4.87; P = .598) was not significantly associated with relapse. Relapse occurred in 40% (2 of 5) with a CFH or MCP variant, 33.3% (2 of 6) with other complement variants, and 0% (0 of 6) with no variants (P = .217). There was no decline in mean glomerular filtration rate from the date of stopping eculizumab until end of follow-up. In summary, eculizumab discontinuation with close monitoring is safe in most patients, with low rates of aHUS relapse and effective salvage with eculizumab retreatment in the event of recurrence.


Assuntos
Síndrome Hemolítico-Urêmica Atípica , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Síndrome Hemolítico-Urêmica Atípica/genética , Proteínas do Sistema Complemento , Taxa de Filtração Glomerular , Humanos , Estudos Prospectivos , Recidiva
10.
Cochrane Database Syst Rev ; 3: CD012862, 2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33783815

RESUMO

BACKGROUND: Atypical haemolytic uraemic syndrome (aHUS) is a rare disorder characterised by thrombocytopenia, microangiopathic haemolytic anaemia, and acute kidney injury. The condition is primarily caused by inherited or acquired dysregulation of complement regulatory proteins with ~40% of those affected aged < 18 years. Historically, kidney failure and death were common outcomes, however, improved understanding of the condition has led to discovery of novel therapies. OBJECTIVES: To evaluate the benefits and harms of interventions for aHUS. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies for randomised controlled studies (RCTs) up to 3 September 2020 using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. MEDLINE(OVID) 1946 to 27 July 2020 and EMBASE (OVID) 1974 to 27 July 2020 were searched for non-RCTs. SELECTION CRITERIA: All randomised and non-randomised clinical trials comparing an intervention with placebo, an intervention with supportive therapy, or two or more interventions for aHUS were included. Given the rare nature of the condition in question, prospective single-arm studies of any intervention for aHUS were also included. DATA COLLECTION AND ANALYSIS: Two authors independently extracted pre-specified data from eligible studies and evaluated risk of bias using a newly developed tool based on existing Cochrane criteria. As statistical meta-analysis was not appropriate, qualitative analysis of data was then performed. MAIN RESULTS: We included five single-arm studies, all of which evaluated terminal complement inhibition for the treatment of aHUS. Four studies evaluated the short-acting C5 inhibitor eculizumab and one study evaluated the longer-acting C5 inhibitor ravulizumab. All included studies within the review were of non-randomised, single-arm design. Thus, risk of bias is high, and it is challenging to draw firm conclusions from this low-quality evidence. One hundred patients were included within three primary studies evaluating eculizumab, with further data reported from 37 patients in a secondary study. Fifty-eight patients were included in the ravulizumab study. After 26 weeks of eculizumab therapy there were no deaths and a 70% reduction in the number of patients requiring dialysis. Complete thrombotic microangiopathic (TMA) response was observed in 60% of patients at 26 weeks and 65% at two years. After 26 weeks of ravulizumab therapy four patients had died (7%) and complete TMA response was observed in 54% of patients. Substantial improvements were seen in estimated glomerular filtration rate and health-related quality of life in both eculizumab and ravulizumab studies. Serious adverse events occurred in 42% of patients, and meningococcal infection occurred in two patients, both treated with eculizumab. AUTHORS' CONCLUSIONS: When compared with historical data, terminal complement inhibition appears to offer favourable outcomes in patients with aHUS, based upon very low-quality evidence drawn from five single-arm studies. It is unlikely that an RCT will be conducted in aHUS and therefore careful consideration of future single-arm data as well as longer term follow-up data will be required to better understand treatment duration, adverse outcomes and risk of disease recurrence associated with terminal complement inhibition.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Inativadores do Complemento/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Síndrome Hemolítico-Urêmica Atípica/mortalidade , Viés , Inativadores do Complemento/efeitos adversos , Taxa de Filtração Glomerular , Humanos , Ensaios Clínicos Controlados não Aleatórios como Assunto , Qualidade de Vida , Microangiopatias Trombóticas/tratamento farmacológico
11.
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
12.
Clin Chim Acta ; 518: 78-82, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33741360

RESUMO

BACKGROUND: The DGKE gene encodes the diacylglycerol kinase epsilon (DGKε). Loss-of-function mutations of DGKE caused a group of rare renal diseases, which are called DGKE nephropathy. We report the clinical manifestations and therapeutic effects of a patient diagnosed with DGKE nephropathy. CASE REPORT: The patient's initial symptoms were fever, diarrhea, eyelid edema, acute anemia, acute thrombocytopenia, an elevation of plasm D-dimer, proteinuria, microscopic hematuria, without oliguria or renal insufficiency at the age of 7.6 months. Hemolytic uremic syndrome was diagnosed. His proteinuria and hematuria turned out negative 2 months later. Proteinuria was noticed again at the age of 5.5-year old when he was brought to the hospital because of failure to thrive. Since then, he had been noticed with persistent proteinuria. RESULTS: Genetic analysis revealed 2 novel heterozygous mutations on DGKE of the patient. Renal pathology mimicked membrane proliferative glomerulonephritis (MPGN). CONCLUSIONS: After a 5-month treatment of cyclosporine A (CsA), proteinuria and hypoproteinemia have relieved apparently. We also observed an improvement of his growth.


Assuntos
Síndrome Hemolítico-Urêmica Atípica , Hipoproteinemia , Pré-Escolar , Ciclosporina/uso terapêutico , Diacilglicerol Quinase , Humanos , Lactente , Masculino , Proteinúria/tratamento farmacológico
13.
Biomolecules ; 11(2)2021 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-33671302

RESUMO

The complement system is part of the innate immune response, where it provides immediate protection from infectious agents and plays a fundamental role in homeostasis. Complement dysregulation occurs in several diseases, where the tightly regulated proteolytic cascade turns offensive. Prominent examples are atypical hemolytic uremic syndrome, paroxysmal nocturnal hemoglobinuria and Alzheimer's disease. Therapeutic intervention targeting complement activation may allow treatment of such debilitating diseases. In this review, we describe a panel of complement targeting nanobodies that allow modulation at different steps of the proteolytic cascade, from the activation of the C1 complex in the classical pathway to formation of the C5 convertase in the terminal pathway. Thorough structural and functional characterization has provided a deep mechanistic understanding of the mode of inhibition for each of the nanobodies. These complement specific nanobodies are novel powerful probes for basic research and offer new opportunities for in vivo complement modulation.


Assuntos
Ativação do Complemento , Proteínas do Sistema Complemento , Nanomedicina/métodos , Anticorpos de Domínio Único/química , Animais , Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Síndrome Hemolítico-Urêmica Atípica/imunologia , Complemento C1/química , Convertases de Complemento C3-C5/química , Epitopos/química , Hemoglobinúria Paroxística/tratamento farmacológico , Hemoglobinúria Paroxística/imunologia , Humanos , Imunidade Inata , Imunoglobulina G/imunologia , Inflamação , Conformação Molecular , Ligação Proteica , Proteólise
14.
BMJ Case Rep ; 14(2)2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33637496

RESUMO

Haemolytic uraemic syndrome (HUS) is a thrombotic microangiopathy (TMA) that presents with renal insufficiency, thrombocytopaenia and microangiopathic haemolytic anaemia. Typical HUS is associated with Shiga toxin while atypical HUS (aHUS) is due to overactivation of the alternative complement pathway. aHUS has numerous causes, including drugs, with rare reports of carfilzomib, a proteasome inhibitor used in multiple myeloma, as causative agent. Cases vary in presentation, presenting a diagnostic challenge. Historically, TMAs were treated with plasma exchange. aHUS, however, is considered refractory to plasma exchange and best treated with eculizumab, a monoclonal antibody targeting C5, a terminal complement protein. We report a patient with history of multiple myeloma who presented with headaches, elevated blood pressure, petechiae, ecchymosis and haemolytic anaemia. His condition was determined to be carfilzomib-induced aHUS and he was successfully treated with eculizumab. Early detection and treatment of drug-induced aHUS is vital in reducing morbidity and mortality related to the condition.


Assuntos
Síndrome Hemolítico-Urêmica Atípica , Púrpura Trombocitopênica Trombótica , Microangiopatias Trombóticas , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Humanos , Masculino , Oligopeptídeos/efeitos adversos
15.
BMC Ophthalmol ; 21(1): 65, 2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-33516177

RESUMO

BACKGROUND: Hemolytic Uremic Syndrome (HUS) is a rare disorder characterized by the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure, considered within the group of thrombocytic microangiopathies. Ocular complications in HUS are very rare. Here, we report an adult patient who suffered from acute onset of paracentral scotoma, caused by branch retinal artery occlusion (BRAO), as a leading symptom of atypical HUS. CASE PRESENTATION: A 39-year-old healthy male was lately diagnosed with essential hypertension and mild renal impairment. He complained about acute onset of central scotoma in his left eye. Fundus examination revealed marked narrowing of retinal vessels, cotton wool spots and few retinal hemorrhages in both eyes. The patient was diagnosed with bilateral ischemic retinal vasculopathy and acute macular BRAO in his left eye. Workup revealed thrombocytopenia, worsening renal failure. Renal biopsy showed signs of chronic thrombotic microangiopathy. The patient was diagnosed with atypical HUS (aHUS) and started on plasmapheresis, together with eculizumab. As his condition continued to worsen, he was put on renal replacement therapy. Due to a persistent monoclone of IgG1, the patient underwent bone marrow biopsy which revealed Monoclonal Gammopathy of renal significance, triggering a HUS and treatment was initiated accordingly. Two months after initial presentation, the patient developed neovascularization of the optic disc (NVD) in his left eye, and was treated with 3 monthly intravitreal bevacizumab injections with complete regression of the NVD. The patient suffered from myocardial infarction in the later course and was lost for follow-up. He returned 11 months after the last bevacizumab injection because of sudden loss of vision in his left eye caused by a dense vitreous hemorrhage. Biomicroscopy revealed a new NVD in his right eye. The patient underwent panretinal photocoagulation in both eyes with regression of neovascularization. Vision improved and remained 20/20 in both eyes. CONCLUSION: We present a case report showing retinal ischemia can be linked with aHUS. As clinal diagnosis might be challenging, physicians should be aware of the rare ocular manifestations of this devastating multi-organ disease. In case of retinal ischemia, panretinal photocoagulation should be initiated soon to avoid blinding complications.


Assuntos
Síndrome Hemolítico-Urêmica Atípica , Oclusão da Artéria Retiniana , Doenças Retinianas , Adulto , Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Humanos , Masculino , Oclusão da Artéria Retiniana/diagnóstico , Oclusão da Artéria Retiniana/etiologia , Hemorragia Retiniana/diagnóstico , Hemorragia Retiniana/etiologia , Hemorragia Vítrea
17.
Kidney Int ; 100(1): 225-237, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33307104

RESUMO

Ravulizumab, a long-acting complement C5 inhibitor engineered from eculizumab, allows extending maintenance dosing from every 2-3 weeks to every 4-8 weeks depending on bodyweight. Here, we evaluated the efficacy and safety of ravulizumab in complement inhibitor-naïve children (under 18 years) with atypical hemolytic uremic syndrome. In this phase III, single-arm trial, ravulizumab was administered every eight weeks in patients 20 kg and over, and four weeks in patients under 20 kg. The primary endpoint was a complete thrombotic microangiopathy response (normalization of platelet count and lactate dehydrogenase, and a 25% or more improvement in serum creatinine) through 26 weeks. Secondary endpoints included change in hematologic parameters and kidney function. 18 patients with a median age of 5.2 years were evaluated. At baseline, symptoms of atypical hemolytic uremic syndrome outside the kidney were present in 72.2% of patients and 38.9% had been in intensive care. Baseline estimated glomerular filtration rate was 22 mL/min/1.73 m2. By week 26, 77.8% of patients achieved a complete thrombotic microangiopathy response; 94.4%, 88.9% and 83.3% of patients achieved platelet normalization, lactate dehydrogenase normalization and a 25% or more improvement in serum creatinine, respectively. By week 50, 94.4% patients had achieved a complete thrombotic microangiopathy response. Median improvement in platelet count was 246 and 213 x109/L through week 26 and week 50, respectively. The median increase above baseline in estimated glomerular filtration rate was 80 and 94 mL/min/1.73m2 through week 26 and week 50, respectively. No unexpected adverse events, deaths, or meningococcal infections occurred. Thus, ravulizumab rapidly improved hematologic and kidney parameters with no unexpected safety concerns in complement inhibitor-naïve children with atypical hemolytic uremic syndrome.


Assuntos
Síndrome Hemolítico-Urêmica Atípica , Microangiopatias Trombóticas , Adolescente , Anticorpos Monoclonais Humanizados , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Criança , Pré-Escolar , Complemento C5 , Inativadores do Complemento/efeitos adversos , Humanos , Microangiopatias Trombóticas/diagnóstico , Microangiopatias Trombóticas/tratamento farmacológico
18.
Intern Med ; 60(6): 917-922, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33087669

RESUMO

Patients with atypical hemolytic uremic syndrome (aHUS) associated with a C3 p.Ile1157Thr mutation show a relatively high renal survival and low mortality rates, but renal histopathological findings after recurrence have been rarely reported. A 30-year-old man with a C3 p.Ile1157Thr mutation experienced a third recurrence of thrombotic microangiopathies with neurological and gastrointestinal disorders. A renal biopsy performed during the recovery phase of acute kidney injury revealed collapsed glomeruli and arteriolar vacuolization. Approximately 10% of glomeruli were globally sclerotic, despite the absence of arterio-/arteriolo-sclerosis. These findings suggest substantial progression of irreversible injuries in multiple organs, including kidneys, which occurs in aHUS patients with repeated thrombotic microangiopathies.


Assuntos
Injúria Renal Aguda , Síndrome Hemolítico-Urêmica Atípica , Microangiopatias Trombóticas , Injúria Renal Aguda/genética , Adulto , Síndrome Hemolítico-Urêmica Atípica/genética , Humanos , Rim , Masculino , Mutação
19.
Eur J Ophthalmol ; 31(2): NP63-NP66, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31875682

RESUMO

PURPOSE: We present the case of a 22-year-old woman, diagnosed as having atypical hemolytic uremic syndrome with a hypertensive crisis, who presented a bilateral serous retinal detachment. CASE DESCRIPTION: A 22-year-old woman, diagnosed as having atypical hemolytic uremic syndrome, was referred for blurred vision in both eyes, evolving over 7 days. Treatment including hemodialysis, plasma exchange, systemic steroids, antihypertensive medications and eculizumab was started 1 month prior to referral. At presentation, best-corrected visual acuity was 20/40 in the right eye and 20/25 in the left eye. Retinal examination revealed bilateral serous retinal detachment in the posterior pole and some small, flat, variably pigmented lesions. Optical coherence tomography confirmed marked serous retinal detachment in both eyes. Fluorescein and indocyanine green angiography was performed. Treatment for systemic hypertension was changed. Seven days later, dilated fundus examination and optical coherence tomography demonstrated a significant regression of the serous retinal detachment. Her visual acuity improves in both eyes at the last control, showing at fundus examination a complete resolution of the exudative detachment but a persistence of variable flat pigmented lesion. CONCLUSION: Although multiple organ systems are commonly affected in hemolytic uremic syndrome, ocular involvement has only been described in very few cases. Ocular manifestations in atypical hemolytic uremic syndrome include retinal, choroidal and vitreal hemorrhages, retina and/or ischemic signs. Bilateral serous retinal detachment may also be a sign of atypical hemolytic uremic syndrome or even the first manifestation of a hypertensive event.


Assuntos
Síndrome Hemolítico-Urêmica Atípica/complicações , Doenças da Coroide/etiologia , Hipertensão/diagnóstico , Hipertensão/etiologia , Descolamento Retiniano/etiologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Doenças da Coroide/diagnóstico , Doenças da Coroide/tratamento farmacológico , Corantes/administração & dosagem , Inativadores do Complemento/uso terapêutico , Feminino , Angiofluoresceinografia , Glucocorticoides/uso terapêutico , Humanos , Hipertensão/tratamento farmacológico , Verde de Indocianina/administração & dosagem , Troca Plasmática , Diálise Renal , Descolamento Retiniano/diagnóstico por imagem , Tomografia de Coerência Óptica , Acuidade Visual/fisiologia , Adulto Jovem
20.
Pediatrics ; 147(2)2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33037119

RESUMO

This is a novel case of a 16-month-old boy with a history of prematurity with intrauterine growth restriction, severe failure to thrive, microcephaly, pachygyria, agenesis of the corpus callosum, and postnatal embolic stroke, who presented with new-onset diabetes mellitus with diabetic ketoacidosis in the setting of severe acute respiratory syndrome coronavirus 2 infection, with a course complicated by atypical hemolytic syndrome (aHUS). This patient demonstrated remarkable insulin resistance in the period before aHUS diagnosis, which resolved with the first dose of eculizumab therapy. There is increasing evidence that COVID-19 is associated with thrombotic disorders and that microangiopathic processes and complement-mediated inflammation may be implicated. In this case report, we describe a pediatric patient with COVID-19 and a new complement-mediated microangiopathic thrombotic disease. Because whole-exome sequencing and extensive workup returned without a clear etiology for aHUS, this is likely a COVID-19 triggered case of aHUS versus an idiopathic case that was unmasked by the infection.


Assuntos
Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Síndrome Hemolítico-Urêmica Atípica/etiologia , COVID-19/complicações , Diabetes Mellitus Tipo 1/diagnóstico , Cetoacidose Diabética/diagnóstico , Anormalidades Múltiplas , Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , COVID-19/diagnóstico , Pré-Escolar , Diabetes Mellitus Tipo 1/complicações , Cetoacidose Diabética/complicações , Humanos , Recém-Nascido Prematuro , Resistência à Insulina , Masculino , Fatores de Risco , SARS-CoV-2
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