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1.
J Med Virol ; 96(6): e29742, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38874263

RESUMO

Polyomaviruses BK (BKPyV) and JC (JCPyV), belonging to the Polyomaviridae, are responsible for human pathologies. In kidney transplant recipients, BKPyV replication can lead to irreversible nephron damage whereas JCPyV replication remains asymptomatic. Concomitant replication is rare and potential competition between the infections has been described. The aim of this retrospective case-control study was to describe the molecular epidemiology and risk factors associated with BKPyV and JCPyV replication in a cohort of kidney transplant recipients. In total, 655 urine samples from 460 patients were tested for BKPyV and JCPyV DNA. Positive samples were submitted to strain genotyping. Demographic and clinical characteristics were also compared. Isolated JCPyV and BKPyV was found in 16.5% and 23.3% of patients, respectively; co-replication was rare (3.9%). BKPyV strains Ib-2, Ib-1, and IVc-2 were the most prevalent. JCPyV strains mostly belonged to genotypes 4 and 1B. During follow-up, JCPyV shedding significantly reduced the risk of BKPyV DNAuria, with an odds ratio of 0.57 (95% confidence interval: 0.35-0.99), and was associated with better prognosis than BKPyV replication, based on the estimated glomerular filtration rate. Molecular epidemiology of BKPyV and JCPyV strains in our region was similar to previous studies. This study suggests that JCPyV is benign and appears to limit damaging BKPyV replication. JCPyV DNAuria screening could thus be a useful strategy to predict BKPyV-related outcomes.


Assuntos
Vírus BK , Genótipo , Vírus JC , Transplante de Rim , Epidemiologia Molecular , Infecções por Polyomavirus , Humanos , Vírus BK/genética , Vírus BK/isolamento & purificação , Infecções por Polyomavirus/epidemiologia , Infecções por Polyomavirus/virologia , Infecções por Polyomavirus/urina , Transplante de Rim/efeitos adversos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Vírus JC/genética , Vírus JC/isolamento & purificação , Estudos de Casos e Controles , Adulto , Eliminação de Partículas Virais , Idoso , Transplantados/estatística & dados numéricos , Infecções Tumorais por Vírus/epidemiologia , Infecções Tumorais por Vírus/virologia , Infecções Tumorais por Vírus/urina , DNA Viral/urina , DNA Viral/genética , Aloenxertos/virologia
2.
Am J Transplant ; 23(3): 366-376, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36695682

RESUMO

Vitamin D sufficiency is associated with a reduced risk of fractures, diabetes mellitus, cardiovascular events, and cancers, which are frequent complications after renal transplantation. The VITALE (VITamin D supplementation in renAL transplant recipients) study is a multicenter double-blind randomized trial, including nondiabetic adult renal transplant recipients with serum 25-hydroxy vitamin D (25(OH) vitamin D) levels of <30 ng/mL, which is randomized 12 to 48 months after transplantation to receive high (100 000 IU) or low doses (12 000 IU) of cholecalciferol every 2 weeks for 2 months and then monthly for 22 months. The primary outcome was a composite endpoint, including diabetes mellitus, major cardiovascular events, cancer, and death. Of 536 inclusions (50.8 [13.7] years, 335 men), 269 and 267 inclusions were in the high-dose and low-dose groups, respectively. The serum 25(OH) vitamin D levels increased by 23 versus 6 ng/mL in the high-dose and low-dose groups, respectively (P < .0001). In the intent-to-treat analysis, 15% versus 16% of the patients in the high-dose and low-dose groups, respectively, experienced a first event of the composite endpoint (hazard ratio, 0.94 [0.60-1.48]; P = .78), whereas 1% and 4% of patients in the high-dose and low-dose groups, respectively, experienced an incident symptomatic fracture (odds ratio, 0.24 [0.07-0.86], P = .03). The incidence of adverse events was similar between the groups. After renal transplantation, high doses of cholecalciferol are safe but do not reduce extraskeletal complications (trial registration: ClinicalTrials.gov; identifier: NCT01431430).


Assuntos
Doenças Cardiovasculares , Transplante de Rim , Deficiência de Vitamina D , Masculino , Adulto , Humanos , Colecalciferol/efeitos adversos , Transplante de Rim/efeitos adversos , Vitamina D/uso terapêutico , Vitaminas/efeitos adversos , Método Duplo-Cego , Suplementos Nutricionais , Doenças Cardiovasculares/etiologia , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/tratamento farmacológico
3.
Blood ; 137(18): 2438-2449, 2021 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-33270832

RESUMO

The optimal duration of eculizumab treatment in patients with atypical hemolytic uremic syndrome (aHUS) remains poorly defined. We conducted a prospective national multicenter open-label study to assess eculizumab discontinuation in children and adults with aHUS. Fifty-five patients (including 19 children) discontinued eculizumab (mean treatment duration, 16.5 months). Twenty-eight patients (51%) had rare variants in complement genes, mostly in MCP (n = 12; 22%), CFH (n = 6; 11%), and CFI (n = 6; 10%). At eculizumab discontinuation, 17 (30%) and 4 patients (7%) had stage 3 and 4 chronic kidney disease, respectively. During follow-up, 13 patients (23%; 6 children and 7 adults) experienced aHUS relapse. In multivariable analysis, female sex and presence of a rare variant in a complement gene were associated with an increased risk of aHUS relapse, whereas requirement for dialysis during a previous episode of acute aHUS was not. In addition, increased sC5b-9 plasma level at eculizumab discontinuation was associated with a higher risk of aHUS relapse in all patients and in the subset of carriers with a complement gene rare variant, both by log-rank test and in multivariable analysis. Of the 13 relapsing patients, all of whom restarted eculizumab, 11 regained their baseline renal function and 2 had a worsening of their preexisting chronic kidney disease, including 1 patient who progressed to end-stage renal disease. A strategy of eculizumab discontinuation in aHUS patients based on complement genetics is reasonable and safe. It improves the management and quality of life of a sizeable proportion of aHUS patients while reducing the cost of treatment. This trial was registered at www.clinicaltrials.gov as #NCT02574403.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Inativadores do Complemento/uso terapêutico , Suspensão de Tratamento/estatística & dados numéricos , Adolescente , Adulto , Síndrome Hemolítico-Urêmica Atípica/metabolismo , Síndrome Hemolítico-Urêmica Atípica/patologia , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida , Adulto Jovem
4.
Blood ; 137(6): 733-742, 2021 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-33150928

RESUMO

The anti-von Willebrand factor nanobody caplacizumab was licensed for adults with immune-mediated thrombotic thrombocytopenic purpura (iTTP) based on prospective controlled trials. However, few data are available on postmarketing surveillance. We treated 90 iTTP patients with a compassionate frontline triplet regimen associating therapeutic plasma exchange (TPE), immunosuppression with corticosteroids and rituximab, and caplacizumab. Outcomes were compared with 180 historical patients treated with the standard frontline treatment (TPE and corticosteroids, with rituximab as salvage therapy). The primary outcome was a composite of refractoriness and death within 30 days since diagnosis. Key secondary outcomes were exacerbations, time to platelet count recovery, the number of TPE, and the volume of plasma required to achieve durable remission. The percentage of patients in the triplet regimen with the composite primary outcome was 2.2% vs 12.2% in historical patients (P = .01). One elderly patient in the triplet regimen died of pulmonary embolism. Patients from this cohort experienced less exacerbations (3.4% vs 44%, P < .01); they recovered durable platelet count 1.8 times faster than historical patients (95% confidence interval, 1.41-2.36; P < .01), with fewer TPE sessions and lower plasma volumes (P < .01 both). The number of days in hospital was 41% lower in the triplet regimen than in the historical cohort (13 vs 22 days; P < .01). Caplacizumab-related adverse events occurred in 46 patients (51%), including 13 major or clinically relevant nonmajor hemorrhagic events. Associating caplacizumab to TPE and immunosuppression, by addressing the 3 processes of iTTP pathophysiology, prevents unfavorable outcomes and alleviates the burden of care.


Assuntos
Corticosteroides/uso terapêutico , Troca Plasmática , Púrpura Trombocitopênica Trombótica/terapia , Rituximab/uso terapêutico , Anticorpos de Domínio Único/uso terapêutico , Proteína ADAMTS13/sangue , Adulto , Terapia Combinada , Ensaios de Uso Compassivo , Progressão da Doença , Quimioterapia Combinada , Feminino , Hemorragia/induzido quimicamente , Estudo Historicamente Controlado , Humanos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Estudos Prospectivos , Púrpura Trombocitopênica Trombótica/sangue , Púrpura Trombocitopênica Trombótica/tratamento farmacológico , Púrpura Trombocitopênica Trombótica/mortalidade , Índice de Gravidade de Doença , Anticorpos de Domínio Único/efeitos adversos , Anticorpos de Domínio Único/economia , Tromboembolia/etiologia , Resultado do Tratamento , Fator de von Willebrand/antagonistas & inibidores
5.
Nephrol Dial Transplant ; 37(4): 781-788, 2022 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-34586413

RESUMO

OBJECTIVES: BK polyomavirus-associated nephropathy is a troublesome disease caused by BK polyomavirus (BKPyV) infection in immunocompromised renal graft recipients. There are no effective treatments available, making immunosuppression reduction the only management option. Thus, pre-graft predictive BKPyV replication markers are needed for identification of patients at high risk of viraemia. METHODS: We conducted a retrospective study to assess the correlation between pre-transplantation BKPyV serostatus and post-transplantation incidence of BKPyV infection. Sera from 329 recipients and 222 matched donors were tested for anti-BKPyV antibodies against BKPyV serotypes I and IV by using a virus-like particle-based immunoglobulin G enzyme-linked immunosorbent assay, and BKPyV DNA load was monitored for at least 1 year post-transplantation. RESULTS: Eighty recipients were viruric and 59 recipients were viraemic post-transplantation. In the post-transplantation period, the probability of developing viraemia for serotype I increased from 4.3% for the D-/R+ group to 12.1% for the D+/R+ group, climbing to 37.5% for the D+/R- group (P < 0.05). When calculating recipient mean titres for serotypes I and IV, we observed a clear difference in the proportions of viraemia, decreasing from 50% for mean titres <400 to 13.5% for titres ≥400 (P < 0.001), as well as a higher proportion of presumptive nephropathy (50% versus 23.1%, respectively; P < 0.05). In univariate analysis, this parameter had an odds ratio of 6.41 for the risk of developing post-transplantation BKPyV viraemia (95% confidence interval 3.16-13.07; P < 0.0001). CONCLUSIONS: Determination of both donor and recipient BKPyV seropositivity before transplantation and antibody titre measurements may serve as a predictive tool to manage clinical BKPyV infection by identification of patients at high risk.


Assuntos
Vírus BK , Transplante de Rim , Infecções por Polyomavirus , Infecções Tumorais por Vírus , Feminino , Humanos , Transplante de Rim/efeitos adversos , Masculino , Infecções por Polyomavirus/diagnóstico , Infecções por Polyomavirus/epidemiologia , Infecções por Polyomavirus/etiologia , Estudos Retrospectivos , Transplantados , Infecções Tumorais por Vírus/diagnóstico , Infecções Tumorais por Vírus/epidemiologia , Infecções Tumorais por Vírus/etiologia , Viremia/diagnóstico , Viremia/epidemiologia , Viremia/etiologia
6.
Emerg Infect Dis ; 27(7): 1876-1885, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34152955

RESUMO

We conducted a retrospective study on hemolytic uremic syndrome caused by Shiga toxin-producing Escherichia coli (STEC) in 96 adults enrolled in the cohort of the National Reference Center for Thrombotic Microangiopathies network in France during 2009-2017. Most infections were caused by STEC strains not belonging to the O157 or O104 serogroups. Thirty (31.3%) patients had multiple risk factors for thrombotic microangiopathy. In total, 61 (63.5%) patients required dialysis, 50 (52.1%) had a serious neurologic complication, 34 (35.4%) required mechanical ventilation, and 19 (19.8%) died during hospitalization. We used multivariate analysis to determine that the greatest risk factors for death were underlying immunodeficiency (hazard ratio 3.54) and severe neurologic events (hazard ratio 3.40). According to multivariate analysis and propensity score-matching, eculizumab treatment was not associated with survival. We found that underlying conditions, especially immunodeficiency, are strongly associated with decreased survival in adults who have hemolytic uremic syndrome caused by STEC.


Assuntos
Infecções por Escherichia coli , Síndrome Hemolítico-Urêmica , Escherichia coli Shiga Toxigênica , Adulto , França , Humanos , Estudos Retrospectivos , Toxina Shiga
7.
Blood ; 134(24): 2209-2217, 2019 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-31530564

RESUMO

Older age is associated with increased mortality in immune thrombotic thrombocytopenic purpura (iTTP). Yet, data are scarce regarding iTTP occurring among older patients. To assess clinical features and long-term impact of iTTP on mortality in older patients (>60 years old), characteristics and prognoses of adult iTTP patients enrolled in the French Reference Center for Thrombotic Microangiopathies registry between 2000 and 2016 were described according to age (<60 years old or ≥60 years old). Long-term mortality of iTTP older survivors was compared with that of non-iTTP geriatric subjects. Comparing, respectively, older iTTP patients (N = 71) with younger patients (N = 340), time from hospital admission to diagnosis was longer (P < .0001); at diagnosis, delirium (P = .034), behavior impairment (P = .045), renal involvement (P < .0001), and elevated troponin level (P = .025) were more important whereas cytopenias were less profound (platelet count, 22 × 103/mm3 [9-57] vs 13 × 103/mm3 [9-21], respectively [P = .002]; hemoglobin level, 9 g/dL [8-11] vs 8 g/dL [7-10], respectively [P = .0007]). Short- and mid-term mortalities were higher (P < .0001) and increased for every 10 years of age range. Age ≥60 years, cardiac involvement, increased plasma creatinine level, and total plasma exchange volume were independently associated with 1-month mortality. Compared with a non-iTTP geriatric population, older survivors showed an increased long-term mortality (hazard ratio = 3.44; P < .001). In conclusion, older iTTP patients have atypical neurological presentation delaying the diagnosis. Age negatively impacts short-term but also long-term mortality.


Assuntos
Púrpura Trombocitopênica Idiopática/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Terapia Combinada , Comorbidade , Gerenciamento Clínico , Feminino , França/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Prognóstico , Vigilância em Saúde Pública , Púrpura Trombocitopênica Idiopática/diagnóstico , Púrpura Trombocitopênica Idiopática/mortalidade , Púrpura Trombocitopênica Idiopática/terapia , Sistema de Registros , Análise de Sobrevida , Avaliação de Sintomas
8.
BMC Nephrol ; 22(1): 267, 2021 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-34284729

RESUMO

BACKGROUND: Gemcitabine is a broadly prescribed chemotherapy, the use of which can be limited by renal adverse events, including thrombotic microangiopathy (TMA). METHODS: This study evaluated the efficacy of eculizumab, a monoclonal antibody targeting the terminal complement pathway, in patients with gemcitabine-induced TMA (G-TMA). We conducted an observational, retrospective, multicenter study in 5 French centres, between 2011 and 2016. RESULTS: Twelve patients with a G-TMA treated by eculizumab were included. The main characteristics were acute renal failure (100%), including stage 3 acute kidney injury (AKI, 58%) and renal replacement therapy (17%), hypertension (92%) and diffuse oedema (83%). Eculizumab was started after a median of 15 days (range 4-44) following TMA diagnosis. A median of 4 injections of eculizumab was performed (range 2-22). Complete hematological remission was achieved in 10 patients (83%) and blood transfusion significantly decreased after only one injection of eculizumab (median of 3 packed red blood cells (range 0-10) before treatment vs 0 (range 0-1) after one injection, P < 0.001). Two patients recovered completely renal function (17%), and 8 achieved a partial remission (67%). Compared to a control group of G-TMA without use of eculizumab, renal outcome was more favourable. At the end of the follow up, median eGFR was 45 vs 33 ml/min/1.73m2 respectively in the eculizumab group and in the control group. CONCLUSIONS: These results suggest that eculizumab is efficient on haemolysis and reduces transfusion requirement in G-TMA. Moreover, eculizumab may improve renal function recovery.


Assuntos
Injúria Renal Aguda , Anticorpos Monoclonais Humanizados/administração & dosagem , Microangiopatias Trombóticas , Injúria Renal Aguda/complicações , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/terapia , Antimetabólitos Antineoplásicos/efeitos adversos , Antimetabólitos Antineoplásicos/uso terapêutico , Transfusão de Sangue/métodos , Transfusão de Sangue/estatística & dados numéricos , Inativadores do Complemento/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Feminino , França/epidemiologia , Humanos , Testes de Função Renal/métodos , Masculino , Pessoa de Meia-Idade , Recuperação de Função Fisiológica , Indução de Remissão/métodos , Terapia de Substituição Renal/métodos , Microangiopatias Trombóticas/diagnóstico , Microangiopatias Trombóticas/etiologia , Microangiopatias Trombóticas/terapia , Resultado do Tratamento , Gencitabina
9.
Blood ; 132(20): 2143-2153, 2018 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-30201758

RESUMO

Preemptive rituximab infusions prevent relapses in immune thrombotic thrombocytopenic purpura (iTTP) by maintaining normal ADAMTS13 activity. However, the long-term outcome of these patients and the potential adverse events of this strategy need to be determined. We report the long-term outcome of 92 patients with iTTP in clinical remission who received preemptive rituximab after identification of severe ADAMTS13 deficiency (activity <10%) during the follow-up. Thirty-seven patients had >1 iTTP episode, and the median cumulative relapse incidence before preemptive rituximab was 0.33 episode per year (interquartile range [IQR], 0.23-0.66). After preemptive rituximab, the median cumulative relapse incidence in the whole population decreased to 0 episodes per year (IQR, 0-1.32; P < .001). After preemptive rituximab, ADAMTS13 activity recovery was sustained in 34 patients (37%) during a follow-up of 31.5 months (IQR, 18-65), and severe ADAMTS13 deficiency recurred in 45 patients (49%) after the initial improvement. ADAMTS13 activity usually improved with additional courses of preemptive rituximab. In 13 patients (14%), ADAMTS13 activity remained undetectable after the first rituximab course, but retreatment was efficient in 6 of 10 cases. In total, 14 patients (15%) clinically relapsed, and 19 patients (20.7%) experienced benign adverse effects. Preemptive rituximab treatment was associated with a change in ADAMTS13 conformation in respondent patients. Finally, in the group of 23 historical patients with iTTP and persistently undetectable ADAMTS13 activity, 74% clinically relapsed after a 7-year follow-up (IQR, 5-11). In conclusion, persistently undetectable ADAMTS13 activity in iTTP during remission is associated with a higher relapse rate. Preemptive rituximab reduces clinical relapses by maintaining a detectable ADAMTS13 activity with an advantageous risk-benefit balance.


Assuntos
Fatores Imunológicos/uso terapêutico , Púrpura Trombocitopênica Trombótica/tratamento farmacológico , Rituximab/uso terapêutico , Prevenção Secundária/métodos , Proteína ADAMTS13/química , Proteína ADAMTS13/deficiência , Proteína ADAMTS13/metabolismo , Adulto , Feminino , Humanos , Fatores Imunológicos/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Conformação Proteica/efeitos dos fármacos , Púrpura Trombocitopênica Trombótica/metabolismo , Rituximab/efeitos adversos , Resultado do Tratamento
10.
Am J Hematol ; 92(4): 381-387, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28133771

RESUMO

Thrombotic thrombocytopenic purpura (TTP) has a devastating prognosis without adapted management. Sources of misdiagnosis need to be identified to avoid delayed treatment. We studied 84 patients with a final diagnosis of severe (<10%) acquired ADAMTS13 deficiency-associated TTP from our National database that included 423 patients, who had an initial misdiagnosis (20% of all TTP). Main diagnostic errors were attributed to autoimmune thrombocytopenia, associated (51%) or not (37%) with autoimmune hemolytic anemia. At admission, misdiagnosed patients were more frequently females (P = .034) with a history of autoimmune disorder (P = .017) and had organ involvement in 67% of cases; they had more frequently antinuclear antibodies (P = .035), a low/undetectable schistocyte count (P = .001), a less profound anemia (P = .008), and a positive direct antiglobulin test (DAT) (P = .008). In multivariate analysis, female gender (P = .022), hemoglobin level (P = .028), a positive DAT (P = .004), and a low schistocytes count on diagnosis (P < .001) were retained as risk factors of misdiagnosis. Platelet count recovery was significantly longer in the misdiagnosed group (P = .041) without consequence on mortality, exacerbation and relapse. However, patients in the misdiagnosed group had a less severe disease than those in the accurately diagnosed group, as evidenced by less organ involvement at TTP diagnosis (P = .006). TTP is frequently misdiagnosed with autoimmune cytopenias. A low schistocyte count and a positive DAT should not systematically rule out TTP, especially when associated with organ failure.


Assuntos
Erros de Diagnóstico , Púrpura Trombocitopênica Idiopática/diagnóstico , Púrpura Trombocitopênica Trombótica/diagnóstico , Proteína ADAMTS13/deficiência , Adulto , Anemia Hemolítica Autoimune/diagnóstico , Anticorpos Antinucleares/análise , Teste de Coombs , Diagnóstico Diferencial , Feminino , Hemoglobinas/análise , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Fatores Sexuais
11.
Blood ; 124(2): 204-10, 2014 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-24869941

RESUMO

In acquired thrombotic thrombocytopenic purpura (TTP), the persistence of severe ADAMTS13 deficiency (<10%) during remission is associated with more relapse. Preemptive (ie, after remission) administration of rituximab in these patients to prevent relapses remains controversial. We performed a cross-sectional analysis of 12-year follow-up data to compare the relapse incidence with or without preemptive rituximab infusion. Among 48 patients who experienced at least one episode of acquired TTP followed by severe ADAMTS13 deficiency during remission, 30 received preemptive rituximab (group 1); the other 18 did not (group 2). After a median of 17 months (interquartile range [IQR], 11-29) following rituximab, the relapse incidence decreased from 0.57 episodes/year (IQR, 0.46-0.7) to 0 episodes/year (IQR, 0-0.81) (P < .01) in group 1. ADAMTS13 activity 3 months after the first rituximab infusion increased to 46% (IQR, 30%-68%). Nine patients required additional courses of rituximab. In 5 patients, ADAMTS13 activity failed to increase durably. Four patients experienced manageable adverse effects. In group 2, the relapse incidence was higher (0.5 relapses/year; IQR, 0.12-0.5; P < .01). Relapse-free survival was longer in group 1 (P = .049). A persistent severe ADAMTS13 deficiency during TTP remission should prompt consideration of preemptive rituximab to prevent relapses.


Assuntos
Anticorpos Monoclonais Murinos/administração & dosagem , Púrpura Trombocitopênica Trombótica/prevenção & controle , Proteínas ADAM/sangue , Proteínas ADAM/deficiência , Proteínas ADAM/imunologia , Proteína ADAMTS13 , Adulto , Autoanticorpos/sangue , Quimioprevenção/métodos , Estudos Transversais , Feminino , Humanos , Infusões Intravenosas , Masculino , Púrpura Trombocitopênica Trombótica/sangue , Indução de Remissão , Estudos Retrospectivos , Rituximab , Prevenção Secundária , Resultado do Tratamento
12.
Eur J Haematol ; 97(2): 183-91, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26608617

RESUMO

BACKGROUND: Daily therapeutic plasma exchange (TPE) and rituximab improved thrombotic thrombocytopenic purpura (TTP) prognosis. In the more severe cases, salvage therapies including twice-daily TPE and/or cyclophosphamide may be proposed and require evaluation. METHODS: TTP was defined as a thrombotic microangiopathy (TMA) with severe (<10%) acquired ADAMTS13 deficiency. Among patients included in the French Reference Center for TMA registry, we considered those with a severe disease (i.e., unresponsive to daily TPE and rituximab) who received twice-daily TPE. RESULTS: Nineteen of 289 (6.6%) patients with TTP were treated by twice-daily TPE between 2008 and 2014. Twice-daily TPE was associated with rituximab in 16 cases. The median duration of twice-daily TPE treatment was 3 d (2-22 d). In 6 patients (31.6%), additional treatments (mainly pulses of cyclophosphamide) were performed because of a persistently refractory disease (4 cases) or an exacerbation (2 cases), despite twice-daily TPE. Only one patient (5.3%) died. The other 18 achieved a durable complete remission 25.5 d (13-68 d) after the first TPE. The median follow-up was 14.4 months (7 d-45 months). CONCLUSIONS: Twice-daily TPE may be an efficient strategy in the more severe TTP patients with a short-term life-threatening disease that could overcome their poor prognosis.


Assuntos
Troca Plasmática , Púrpura Trombocitopênica Trombótica/diagnóstico , Púrpura Trombocitopênica Trombótica/terapia , Adolescente , Adulto , Criança , Feminino , França , Humanos , Masculino , Pessoa de Meia-Idade , Troca Plasmática/métodos , Púrpura Trombocitopênica Trombótica/imunologia , Terapia de Salvação , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto Jovem
13.
Am J Hematol ; 91(12): 1246-1251, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27643485

RESUMO

The standard four-rituximab infusions treatment in acquired thrombotic thrombocytopenic purpura (TTP) remains empirical. Peripheral B cell depletion is correlated with the decrease in serum concentrations of anti-ADAMTS13 and associated with clinical response. To assess the efficacy of a rituximab regimen based on B cell depletion, 24 TTP patients were enrolled in this prospective multicentre single arm phase II study and then compared to patients from a previous study. Patients with a suboptimal response to a plasma exchange-based regimen received two infusions of rituximab 375 mg m-2 within 4 days, and a third dose at day +15 of the first infusion if peripheral B cells were still detectable. Primary endpoint was the assessment of the time required to platelet count recovery from the first plasma exchange. Three patients died after the first rituximab administration. In the remaining patients, the B cell-driven treatment hastened remission and ADAMTS13 activity recovery as a result of rapid anti-ADAMTS13 depletion in a similar manner to the standard four-rituximab infusions schedule. The 1-year relapse-free survival was also comparable between both groups. A rituximab regimen based on B cell depletion is feasible and provides comparable results than with the four-rituximab infusions schedule. This regimen could represent a new standard in TTP. This trial was registered at www.clinicaltrials.gov (NCT00907751). Am. J. Hematol. 91:1246-1251, 2016. © 2016 Wiley Periodicals, Inc.


Assuntos
Linfócitos B/efeitos dos fármacos , Púrpura Trombocitopênica Trombótica/tratamento farmacológico , Rituximab/administração & dosagem , Proteína ADAMTS13/sangue , Adulto , Linfócitos B/patologia , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Estudo Historicamente Controlado , Humanos , Depleção Linfocítica , Masculino , Pessoa de Meia-Idade , Troca Plasmática , Contagem de Plaquetas , Púrpura Trombocitopênica Trombótica/mortalidade , Púrpura Trombocitopênica Trombótica/terapia
14.
Transpl Int ; 29(11): 1168-1175, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27516136

RESUMO

BK virus is a common opportunistic post-transplantation viral infection. Although some risk factors have been studied in this context, the contribution of NK cells has not been assessed in detail. In a group of kidney transplant recipients, we studied the association between (i) the likelihood of BK virus replication during the two-year period after kidney transplantation and (ii) the genotypes of the killer cell immunoglobulin-like receptor (KIR) repertoire and their human leukocyte antigen (HLA) ligands. Other clinical factors (such as defective organ recovery and immunosuppressive treatment) were also assessed. BK virus replication was observed in 43 of the 103 recipients (41%). Patients with BK virus replication in the plasma were more likely to display defective organ recovery in the first seven days post-transplantation. BK virus replication was not associated with Missing KIR ligands. However, BK virus replication was more frequent in patients with responsive NK cells (i.e. when a ligand for activating KIRs was not homozygous in the recipient and present in the donor). Our results suggest that defective organ recovery and the recipient's activating KIR repertoire may be related (depending on HLA ligands present in the couple recipient / donor) to the reactivation of BK virus replication after kidney transplantation.


Assuntos
Transplante de Rim , Infecções por Polyomavirus/virologia , Receptores KIR/genética , Insuficiência Renal/imunologia , Infecções Tumorais por Vírus/virologia , Adulto , Idoso , Vírus BK/imunologia , Vírus BK/fisiologia , Biópsia , Feminino , Genótipo , Rejeição de Enxerto/imunologia , Antígenos HLA/química , Histocompatibilidade , Humanos , Células Matadoras Naturais/imunologia , Masculino , Pessoa de Meia-Idade , Ácidos Nucleicos/metabolismo , Infecções por Polyomavirus/imunologia , Insuficiência Renal/cirurgia , Estudos Retrospectivos , Infecções Tumorais por Vírus/imunologia , Replicação Viral , Adulto Jovem
15.
Transfusion ; 54(2): 389-97, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23711330

RESUMO

BACKGROUND: Infectious events have been reported as major environmental triggers of thrombotic thrombocytopenic purpura (TTP). We detail here the potential association between infections and TTP. STUDY DESIGN AND METHODS: We recruited randomly and prospectively a cohort of 280 consecutive TTP patients during a 9-year period. Features of infection were systematically recorded. RESULTS: Features consistent with an infectious event were observed in 114 patients (41%) at time of TTP diagnosis. Infectious agents were documented in 34 cases and were mainly Gram-negative bacilli. At time of diagnosis infected patients more frequently had fever (p < 0.001). Infections at diagnosis did not impact prognosis and outcome. Thirty-six percent of patients experienced an infectious event during hospitalization, which resulted in more exacerbation of TTP (p = 0.02). Infections were not overrepresented during treatment in patients who received steroids and/or rituximab. Further genetic analysis of toll-like receptor (TLR)-9 functionally relevant polymorphisms revealed that TLR-9 +2848 G and TLR-9 +1174 A genotypes were more frequent in TTP patients than in controls (p = 0.04 and p = 0.026, respectively) and more particularly in patients negative for the Class II human leukocyte antigen system susceptibility allele DRB1*11 (p = 0.001 and p = 0.002, respectively). Haplotypes estimation showed that 1174A-2848G haplotype was significantly more frequent in TTP (p = 0.004), suggesting a primary role for this haplotype variation in conferring a predisposition for acquired TTP. CONCLUSION: Infections should be considered as an aggravating factor during the course of TTP. Particular polymorphisms in TLR-9 gene may represent risk factors for TTP.


Assuntos
Infecções/complicações , Púrpura Trombocitopênica Trombótica/genética , Receptor Toll-Like 9/genética , Adulto , Feminino , França/epidemiologia , Predisposição Genética para Doença , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Prevalência , Estudos Prospectivos , Púrpura Trombocitopênica Trombótica/etiologia , Sistema de Registros , Fatores de Risco , Microangiopatias Trombóticas/epidemiologia , Microangiopatias Trombóticas/genética
16.
Nephrol Dial Transplant ; 29(11): 2084-91, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24920841

RESUMO

BACKGROUND: Minimal-change nephrotic syndrome (MCNS) is a common cause of steroid sensitive nephrotic syndrome (NS) with frequent relapse. Although steroids and calcineurin inhibitors (CNIs) are the cornerstone treatments, the use of rituximab (RTX), a monoclonal antibody targeting B cells, is an efficient and safe alternative in childhood. METHODS: Because data from adults remain sparse, we conducted a large retrospective and multicentric study that included 41 adults with MCNS and receiving RTX. RESULTS: Complete (NS remission and withdrawal of all immunosuppressants) and partial (NS remission and withdrawal of at least one immunosuppressants) clinical responses were obtained for 25 and 7 patients, respectively (overall response 78%), including 3 patients that only received RTX and had a complete clinical response. After a follow-up time of 39 months (6-71), relapses occurred in 18 responder patients [56%, median time 18 months (3-36)]. Seventeen of these received a second course of RTX and then had a complete (n = 13) or partial (n = 4) clinical response. From multivariate analysis, on-going mycophenolate mofetil (MMF) therapy at the time of RTX was the only predictive factor for RTX failure [HR = 0.07 95% CI (0.01-0.04), P = 0.003]. Interestingly, nine patients were still in remission at 14 months (3-36) after B-cell recovery. No significant early or late adverse event occurred after RTX therapy. CONCLUSIONS: RTX is safe and effective in adult patients with MCNS and could be an alternative to steroids or CNIs in patients with a long history of relapsing MCNS.


Assuntos
Anticorpos Monoclonais Murinos/administração & dosagem , Tolerância a Medicamentos , Glucocorticoides/farmacologia , Nefrose Lipoide/tratamento farmacológico , Adolescente , Adulto , Idoso , Antígenos CD20 , Linfócitos B/efeitos dos fármacos , Linfócitos B/imunologia , Biópsia , Criança , Pré-Escolar , Feminino , Humanos , Imunidade Celular/efeitos dos fármacos , Fatores Imunológicos/administração & dosagem , Lactente , Masculino , Pessoa de Meia-Idade , Nefrose Lipoide/imunologia , Nefrose Lipoide/patologia , Indução de Remissão , Estudos Retrospectivos , Rituximab , Fatores de Tempo , Resultado do Tratamento
17.
Clin Nephrol ; 81(3): 210-5, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23073062

RESUMO

CONTEXT: Thrombotic thrombocytopenic purpura (TTP) is a particularly serious form of thrombotic microangiopathy (TMA) due to the risk of multiple organ dysfunction. Several etiological factors such as infection, auto-immune disease, certain medications and cancers have been associated with TTP. CLINICAL CASES: A 74-year-old hypertensive woman with a history of thromboembolic disease was hospitalized for acute kidney injury (AKI) associated with pneumonia. Initial investigations were suggestive of Pneumocystis jirovecii infection and myeloma cast nephropathy. Several days later, the patient presented features of TTP. Von Willebrand factor-cleaving protease activity was less than 5% with a high level of IgG antibody directed against ADAMTS13. Treatment consisted of monthly 4-day cycles of dexamethasone and melphalan in combination with plasmapheresis and resulted in a favorable outcome. Three years after ceasing treatment, the patient presented no signs of hemolysis, but required chronic hemodialysis. CONCLUSION: The association of TMA, especially TTP, and multiple myeloma is exceptional. The authors report such a case that induced irreversible renal damage, but with stable clinical and laboratory parameters with a follow-up of 4 years.


Assuntos
Proteínas ADAM/imunologia , Autoanticorpos/sangue , Imunoglobulina G/sangue , Mieloma Múltiplo/imunologia , Púrpura Trombocitopênica Trombótica/imunologia , Proteína ADAMTS13 , Injúria Renal Aguda/imunologia , Injúria Renal Aguda/terapia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Dexametasona/administração & dosagem , Feminino , Humanos , Melfalan/administração & dosagem , Mieloma Múltiplo/sangue , Mieloma Múltiplo/complicações , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/terapia , Plasmaferese , Púrpura Trombocitopênica Trombótica/sangue , Púrpura Trombocitopênica Trombótica/diagnóstico , Púrpura Trombocitopênica Trombótica/terapia , Diálise Renal , Fatores de Tempo , Resultado do Tratamento
18.
Pathogens ; 13(4)2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38668270

RESUMO

BACKGROUND/OBJECTIVES: In the absence of an effective antiviral treatment for BK polyomavirus (BKPyV), a better understanding of the epidemiology and time course of BKPyV replication after kidney transplantation is needed to limit the virus's impact on the graft outcome. METHODS: In a 7-year study, we screened more than 430 kidney transplant recipients and analyzed the time course and virological characteristics of BKPyV replication. RESULTS: Urinary viral replication was observed in 116 (27%) of the 430 patients, and 90 of the 116 (78%) had viral DNAemia. Thirty-eight patients (8.8%) were presumed to have nephropathy (DNAemia > 4 log10 copies/mL). Of the patients with BKPyV replication, 48%, 60%, 71%, and 80% were first found to be positive one, two, three, and four months post-transplantation. The initial viral load in the urine was below 7 log10 copies/mL in 100% of the patients with viral replication first detected before the first month, and this proportion was 57% when viral replication was first detected after the first month. When the BKPyV replication was first detected in a urine sample at month 3 or later, 81.5% of patients had concomitant BKPyV DNAemia. The predominant viral subtype was Ib2 (60%), and there was no apparent relationship between the subtype and the time course of BKPyV replication. CONCLUSIONS: Urinary BKPyV replication occurs early after renal transplantation and in most patients will increase to a level requiring therapeutic intervention. Close monitoring for BKPyV in the early post-transplantation period would enable the pre-emptive adjustment of the immunosuppression regimen.

19.
Adv Ther ; 40(9): 3956-3970, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37392339

RESUMO

INTRODUCTION: Kidney transplant recipients (KTRs) produce a weak humoral response to coronavirus disease 2019 (COVID-19) vaccines. However, the factors associated with the quality of the serological response to three doses of COVID-19 vaccine have not been unambiguously identified. METHODS: We included KTRs followed in the Nephrology Department at Amiens University Hospital (Amiens, France) between June and December 2021 who had received three doses of a COVID-19 mRNA vaccine (or two doses plus an episode of polymerase chain reaction-confirmed COVID-19). The lack of a humoral response was defined as an antibody titer below 7.1 binding antibody units (BAU)/mL, and an optimal response was defined as an antibody titer above 264 BAU/mL. RESULTS: Of the 371 patients included, 246 (66.3%) were seropositive, and 97 (26.1%) had an optimal response. In a multivariate analysis, the only factor associated with seropositivity was a history of COVID-19 [odds ratio (OR) 87.2; 95% confidence interval (CI) (7.88-965.0); p < 0.0001], while the main factors associated with non-response were female sex [OR 0.28; 95%CI (0.15-0.51); p < 0.0001], less than 36 months between kidney transplantation and vaccination [OR 0.26; 95%CI (0.13-0.52); p < 0.0001], a higher creatinine level [OR 0.33; 95%CI (0.19-0.56); p < 0.0001], the use of tacrolimus [OR 0.23; 95%CI (0.12-0.45); p < 0.0001], the use of belatacept [OR 0.01; 95%CI (0.001-0.20); p = 0.002] and three-drug immunosuppression [OR 0.39; 95%CI (0.19-0.78); p = 0.015]. A history of COVID-19 was associated with an optimal response [OR 4.03; 95%CI (2.09-7.79); p < 0.0001], while an older age at vaccination [OR 0.97; 95%CI (0.95-0.99); p = 0.002], less than 36 months between kidney transplantation and vaccination [OR 0.35; 95%CI (0.18-0.69); p = 0.002], a higher creatinine level [OR 0.60; 95%CI (0.38-0.93); p = 0.02], three-drug immunosuppression [OR 0.45; 95%CI (0.27-0.76); p = 0.003] were associated with a poorer response. CONCLUSION: We identified factors associated with a humoral response to a COVID-19 mRNA vaccine in KTRs. These findings might help physicians to optimize vaccination in KTRs.


Assuntos
COVID-19 , Transplante de Rim , Humanos , Feminino , Masculino , Vacinas contra COVID-19/uso terapêutico , COVID-19/prevenção & controle , Creatinina , Vacinas de mRNA
20.
J Crit Care ; 76: 154283, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36931181

RESUMO

Thrombotic thrombocytopenic purpura (iTTP) and atypical hemolytic-uremic syndrome (aHUS), once in remission, may cause long-term symptoms, among which mental-health impairments may be difficult to detect. We conducted telephone interviews 72 [48-84] months after ICU discharge to assess symptoms of anxiety, depression, and posttraumatic stress disorder (PTSD) and the 36-item Short Form questionnaire (SF-36). Of 103 included patients, 52 had iTTP and 51 aHUS; 74% were female, median age was 39 y (31-54), and 39 (38%) patients were still taking treatment. Symptoms of anxiety, PTSD and depression were present in 50%, 27% and 14% of patients, respectively, with no significant difference between the iTTP and aHUS groups. Patients with PTSD symptoms had significantly greater weight gain and significantly worse perceived physical and/or emotional wellbeing, anxiety symptoms, and depression symptoms. The SF-36 physical and mental components indicated significantly greater quality-of-life impairments in patients with vs. without PTSD symptoms and in those with aHUS and PTSD vs. iTTP with or without PTSD. In the aHUS group, quality of life was significantly better in patients with vs. without eculizumab treatment. Factors independently associated with PTSD symptoms were male sex (odds ratio [OR], 0.11; 95%CI, 0.02-0.53), platelet count ≤20 G/L at acute-episode presentation (OR, 2.68; 1.01-7.38), and current treatment (OR, 2.69; 95%CI, 1.01-7.36). Mental-health screening should be routine in patients with iTTP and aHUS to ensure appropriate care.


Assuntos
Síndrome Hemolítico-Urêmica Atípica , Púrpura Trombocitopênica Trombótica , Transtornos de Estresse Pós-Traumáticos , Humanos , Masculino , Feminino , Adulto , Púrpura Trombocitopênica Trombótica/complicações , Púrpura Trombocitopênica Trombótica/diagnóstico , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Qualidade de Vida , Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Síndrome Hemolítico-Urêmica Atípica/etiologia , Síndrome Hemolítico-Urêmica Atípica/terapia , Sobreviventes
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