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1.
J Autoimmun ; 112: 102467, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32340774

RESUMO

OBJECTIVE: To describe characteristics and long-term outcomes of patients with microscopic polyangiitis (MPA), an antineutrophil cytoplasm antibody (ANCA)-associated small-vessel necrotizing vasculitis. METHODS: MPA patients from the French Vasculitis Study Group Registry satisfying the European Medicines Agency algorithm were analyzed retrospectively. Characteristics at diagnosis, treatments, relapses and deaths were analyzed to identify factors predictive of death or relapse. RESULTS: Between 1966 and 2017, 378 MPA patients (median age 63.7 years) were diagnosed and followed for a mean of 5.5 years. At diagnosis, the main clinical manifestations included renal involvement (74%), arthralgias (45%), skin (41%), lung (40%) and mononeuritis multiplex (32%), with less frequent alveolar hemorrhage (16%), cardiomyopathy (5%) and severe gastrointestinal signs (4%); mean serum creatinine was 217 µmol/L. ANCA were detected in 298/347 (86%) patients by immunofluorescence and/or enzyme-linked immunosorbent assay (ELISA). Among the 293 patients with available ELISA specificities, 272 (92.8%) recognized myeloperoxidase and 13 (4.4%) proteinase-3. During follow-up, 131 (34.7%) patients relapsed and 78 (20.6%) died, mainly from infections. Respective 5-year overall and relapse-free survival rates were 84.2% and 60.4%. Multivariable analyses retained age >65 years, creatinine >130 µmol/L, severe gastrointestinal involvement and mononeuritis multiplex as independent risk factors for death. Renal impairment was associated with a lower risk of relapse. CONCLUSION: Non-renal manifestations and several risk factors for death or relapse were frequent in this nationwide cohort. While mortality was low, and mainly due to treatment-related complications, relapses remained frequent, suggesting that MPA management can be further improved.


Assuntos
Gastroenteropatias/epidemiologia , Poliangiite Microscópica/complicações , Mononeuropatias/epidemiologia , Insuficiência Renal/epidemiologia , Fatores Etários , Idoso , Feminino , França/epidemiologia , Gastroenteropatias/imunologia , Humanos , Masculino , Poliangiite Microscópica/imunologia , Poliangiite Microscópica/mortalidade , Poliangiite Microscópica/terapia , Pessoa de Meia-Idade , Mononeuropatias/imunologia , Recidiva , Sistema de Registros/estatística & dados numéricos , Insuficiência Renal/imunologia , Estudos Retrospectivos , Taxa de Sobrevida
2.
Clin Nephrol ; 89 (2018)(1): 41-49, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28933339

RESUMO

OBJECTIVE: Outcomes of systemic lupus erythematosus (SLE) and lupus nephritis (LN) are highly heterogeneous among some populations because of interactions between genetic, epigenetic, environmental, and socioeconomic factors. A better characterization of social and ethnic disparities in mixed populations may thus help to develop individualized treatment regimens. MATERIALS AND METHODS: Retrospective observational study including all patients with LN diagnosed between January 1993 and January 2014 in the only Nephrology Department of French Polynesia. RESULTS: The annual incidence of SLE and LN in French Polynesia was 3.6 and 0.96 per 100,000, respectively. Among the 45 patients with biopsy-proven LN (pediatric onset, 26.7%), LN occurred during the first SLE flare-up in 68.8%. At presentation, median eGFR was 72 mL/min/1.73m2 (31 - 105), 32 patients had class-III/IV active glomerulonephritis (GN), and 10 had pure or mixed class-V GN. During the follow-up, 5 patients died (11.1%) and 2 reached end-stage renal disease (4.4%). Cumulative incidences of complete and partial renal responses were 31.1% and 40% at 12 months. Complete renal response (CR) was only predicted by renal presentation (lack of leukocyturia, low proteinuria). Among the 36 patients with renal response, 18 relapsed. Maintenance treatment (mycophenolate mofetil) and place of residence (Windward Islands as compared to remote islands) were the only factors that protected from relapse. CONCLUSION: Renal presentation was the main predictive factor for a renal response whereas geographical residence and maintenance-treatment regimen were predictive of LN relapses in patients from French Polynesia, an area characterized by a specific genetic background and including several isolated islands that have limited access to healthcare.
.


Assuntos
Nefrite Lúpica/epidemiologia , Humanos , Incidência , Falência Renal Crônica/epidemiologia , Polinésia/epidemiologia , Estudos Retrospectivos
3.
Kidney Int ; 91(3): 720-728, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28069266

RESUMO

Monoclonal gammopathy of renal significance (MGRS) regroups renal disorders caused by a monoclonal immunoglobulin without overt hematological malignancy. MGRS includes tubular disorders, glomerular disorders with organized deposits, and glomerular disorders with non-organized deposits, such as proliferative glomerulonephritis with monoclonal IgG deposits. Since glomerular involvement related to monotypic IgA deposits is poorly described we performed retrospective analysis and defined clinico-biological characteristics, renal pathology, and outcome in 19 referred patients. This analysis allowed distinction between 2 types of glomerulopathies, α-heavy chain deposition disease (5 patients) and glomerulonephritis with monotypic IgA deposits (14 patients) suggestive of IgA-proliferative glomerulonephritis with monoclonal immunoglobulin deposits in 12 cases. Clinicopathologic characteristics of α-heavy chain deposition disease resemble those of the γ-heavy chain disease, except for a higher frequency of extra-capillary proliferation and extra-renal involvement. IgA-proliferative glomerulonephritis with monoclonal immunoglobulin deposits should be differentiated from diseases with polytypic IgA deposits, given distinct clinical, histological, and pathophysiological features. Similarly to IgG-proliferative glomerulonephritis with monoclonal immunoglobulin deposits, overt hematological malignancy was infrequent, but sensitive serum and bone marrow studies revealed a subtle plasma cell proliferation in most patients with IgA-proliferative glomerulonephritis with monoclonal immunoglobulin deposits. Anti-myeloma agents appeared to favorably influence renal prognosis. Thus, potential progression towards symptomatic IgA multiple myeloma suggests that careful hematological follow-up is mandatory. This series expands the spectrum of renal disease in MGRS.


Assuntos
Glomerulonefrite por IGA/imunologia , Glomerulonefrite/imunologia , Doença das Cadeias Pesadas/imunologia , Imunoglobulina A/análise , Rim/imunologia , Mieloma Múltiplo/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/análise , Biópsia , Proliferação de Células , Diagnóstico Diferencial , Progressão da Doença , Feminino , Imunofluorescência , França , Glomerulonefrite/tratamento farmacológico , Glomerulonefrite/patologia , Glomerulonefrite por IGA/tratamento farmacológico , Glomerulonefrite por IGA/patologia , Doença das Cadeias Pesadas/tratamento farmacológico , Doença das Cadeias Pesadas/patologia , Humanos , Cadeias alfa de Imunoglobulina/análise , Cadeias gama de Imunoglobulina/análise , Rim/efeitos dos fármacos , Rim/ultraestrutura , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/patologia , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Fatores de Tempo
4.
J Autoimmun ; 73: 24-9, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27267459

RESUMO

The overall and renal outcomes of patients with Goodpasture syndrome (GS), a rare autoimmune disorder characterized by circulating anti-GBM antibodies and rapidly progressive glomerulonephritis and/or pulmonary hemorrhage, have mostly been reported in small-sized cohorts or by aggregating patients receiving a variety of therapies that include aggressive (i.e., combined plasma exchanges, corticosteroids, and cyclophosphamide) and less aggressive (i.e., either plasma exchanges or immunosuppressive drugs, or no treatment). To address the prognosis of GS patients with relatively homogeneous management including plasma exchanges, we conducted a multicenter retrospective study on GS patients included in the registry of the French Society of Hemapheresis. 122 patients were included (kidney alone (n = 28), lung alone (n = 5), or combined involvement (n = 89)). All 122 patients received plasma exchanges (median number of sessions: 13 [9-17]), either alone (n = 8) or associated with combined corticosteroids and oral or IV cyclophosphamide (n = 101) or with corticosteroids alone (n = 12) or cyclophosphamide alone (n = 2). One-year survival was 86.9%. 7/16 patients died from severe infection. In multivariate analyses (Cox's regression model), being aged <60 years, and number of plasma exchanges were correlated to overall survival. The use of alternative immunosuppressive drugs (because of refractory or relapsing GS) was correlated to mortality at one year. Superiority of oral cyclophosphamide compared to intravenous intake was close to significant. Using a logistic regression model, renal survival in patients alive at 1 year was only predicted by serum creatinine <500 µmol/L at presentation. This large series describes the predictive factors for overall and renal survival of GS patients treated by plasma exchanges. Interventional studies that compare oral and intravenous cyclophosphamide, as well as testing new immunosuppressive therapies, are warranted.


Assuntos
Doença Antimembrana Basal Glomerular/epidemiologia , Doença Antimembrana Basal Glomerular/terapia , Imunossupressores/uso terapêutico , Sistema de Registros/estatística & dados numéricos , Corticosteroides/uso terapêutico , Adulto , Idoso , Doença Antimembrana Basal Glomerular/sangue , Doença Antimembrana Basal Glomerular/complicações , Autoanticorpos/sangue , Creatinina/sangue , Ciclofosfamida/uso terapêutico , Feminino , Humanos , Incidência , Estimativa de Kaplan-Meier , Rim/imunologia , Rim/patologia , Pulmão/imunologia , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Troca Plasmática , Prognóstico , Estudos Retrospectivos , Adulto Jovem
5.
J Autoimmun ; 65: 49-55, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26330347

RESUMO

The use of plasma exchanges (PLEX) in systemic necrotizing vasculitides (SNV) still need to be codified. To describe indications, efficacy and safety of PLEX for the treatment of SNV, we conducted a multicenter retrospective study on patients with ANCA-associated vasculitis (AAV) or non-viral polyarteritis nodosa (PAN) treated with PLEX. One hundred and fifty-two patients were included: GPA (n = 87), MPA (n = 56), EGPA (n = 4) and PAN (n = 5). PLEX were used for rapidly progressive glomerulonephritis (RPGN) in 126 cases (86%), alveolar hemorrhage in 64 cases (42%), and severe mononeuritis multiplex in 23 cases (15%). In patients with RPGN, there was a significant improvement in renal function compared to baseline value (P < 0.0001), the plateau being reached at month 3 after PLEX initiation, and estimated glomerular filtration rate improved especially as the number of PLEX increased. In patients with alveolar hemorrhage, mechanical ventilation was discontinued in all patients after a median time of 15 days. Patients treated for mononeuritis multiplex showed improvement of severe motor weakness. After a median follow of 22 months, 18 deaths (12%) were recorded, mainly in patients with RPGN and within the first 6 months. Incidence of end-stage renal disease and/or death was similar between groups of different baseline renal function, but was increased in MPO-ANCA compared to PR3-ANCA. Adverse events attributable to PLEX were recorded in 63%. No death occurred during PLEX. This large series describes indications, efficacy and safety of PLEX in daily practice. Randomized controlled studies are ongoing to define optimal indications, PLEX regimen and concomitant medications.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/terapia , Glomerulonefrite/terapia , Hemorragia/terapia , Pneumopatias/terapia , Mononeuropatias/terapia , Troca Plasmática , Poliarterite Nodosa/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/mortalidade , Feminino , França/epidemiologia , Taxa de Filtração Glomerular , Glomerulonefrite/mortalidade , Hemorragia/mortalidade , Humanos , Incidência , Falência Renal Crônica/epidemiologia , Pneumopatias/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
6.
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
7.
Ann Rheum Dis ; 72(11): 1786-92, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23144449

RESUMO

INTRODUCTION: Hydroxychloroquine (HCQ) is an important medication for treating systemic lupus erythematosus (SLE). Its blood concentration ([HCQ]) varies widely between patients and is a marker and predictor of SLE flares. This prospective randomised, double-blind, placebo-controlled, multicentre study sought to compare standard and adjusted HCQ dosing schedules that target [HCQ] ≥1000 ng/ml to reduce SLE flares. PATIENTS AND METHODS: [HCQ] was measured in 573 patients with SLE (stable disease and SELENA-SLEDAI≤12) treated with HCQ for at least 6 months. Patients with [HCQ] from 100 to 750 ng/ml were randomised to one of two treatment groups: no daily dose change (group 1) or increased HCQ dose to achieve the target [HCQ] (group 2). The primary end point was the number of patients with flares during 7 months of follow-up. RESULTS: Overall, mean [HCQ] was 918±451 ng/ml. Active SLE was less prevalent in patients with higher [HCQ]. A total of 171 patients were randomised and followed for 7 months. SLE flare rates were similar in the two groups (25% in group 1 vs 27.6% in group 2; p=0.7), but a significant spontaneous increase in [HCQ] in both groups between inclusion and randomisation strongly suggested improved treatment adherence. Patients at the therapeutic target throughout follow-up tended to have fewer flares than those with low [HCQ] (20.5% vs 35.1%, p=0.12). CONCLUSIONS: Although low [HCQ] is associated with higher SLE activity, adapting the HCQ dose did not reduce SLE flares over a 7-month follow-up.


Assuntos
Antirreumáticos/administração & dosagem , Hidroxicloroquina/administração & dosagem , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Adulto , Antirreumáticos/sangue , Relação Dose-Resposta a Droga , Método Duplo-Cego , Monitoramento de Medicamentos/métodos , Feminino , França , Humanos , Hidroxicloroquina/sangue , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento
8.
Br J Clin Pharmacol ; 76(5): 734-40, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23432476

RESUMO

AIMS: Both rituximab and plasmapheresis can be associated in the treatment of immune-mediated kidney diseases. The real impact of plasmapheresis on rituximab pharmacokinetics is unknown. The aim of this study was to compare rituximab pharmacokinetics between patients requiring plasmapheresis and others without plasmapheresis. METHODS: The study included 20 patients receiving one or several infusions of rituximab. In 10 patients, plasmapheresis sessions were also performed (between two and six sessions per patient). Rituximab concentrations were measured in blood samples in all patients and in discarded plasma obtained by plasmapheresis using an enzyme-linked immunosorbent assay method. Data were analysed according to a population pharmacokinetic approach. RESULTS: The mean percentage of rituximab removed during the first plasmapheresis session ranged between 47 and 54% when plasmapheresis was performed between 24 and 72 h after rituximab infusion. Rituximab pharmacokinetics was adequately described by a two-compartment model with first-order elimination. Plasmapheresis had a significant impact on rituximab pharmacokinetics, with an increase of rituximab clearance by a factor of 261 (95% confidence interval 146-376), i.e. from 6.64 to 1733 ml h(-1) . Plasmapheresis performed 24 h after rituximab infusion decreased the rituximab area under the curve by 26%. CONCLUSIONS: Plasmapheresis removed an important amount of rituximab when performed less than 3 days after infusion. The removal of rituximab led to a significant decrease of the area under the curve. This pharmacokinetic observation should be taken into account for rituximab dosing, e.g. an additional third rituximab infusion may be recommended when three plasmapheresis sessions are performed after the first rituximab infusion.


Assuntos
Anticorpos Monoclonais Murinos/farmacocinética , Fatores Imunológicos/farmacocinética , Nefropatias/terapia , Plasmaferese , Adulto , Área Sob a Curva , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Nefropatias/imunologia , Nefropatias/fisiopatologia , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Rituximab , Fatores de Tempo
9.
J Clin Rheumatol ; 19(3): 142-8, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23519183

RESUMO

Cryofibrinogenemia is a cryoprotein that was first identified in 1955 by Korst and Kratochvil. Unlike cryoglobulin, the precipitate forms only in plasma and not in the serum. The presence of cryofibrinogen in plasma can be asymptomatic. Cryofibrinogenemia is considered a rare disorder: its prevalence varies from 0% to 7% in healthy subjects and from 8% to 13% in hospitalized patients. Nevertheless, cryofibrinogenemia, when a cryopathy is clinically suspected, has been reported in 12% to 51% of patients. Skin manifestations are usually the first signs and are usually moderate; in addition, cold intolerance, Raynaud phenomenon, purpura, or livedo reticularis often occurs. Skin necrosis, acral ulcers, and gangrene can lead to surgery and amputation. Systemic manifestations are common, and arterial or venous thrombotic events are frequent. Cryofibrinogenemia may be primary (essential) or secondary to other underlying disorders, such as carcinoma, infection, vasculitis, collagen disease, or associated with cryoglobulinemia. The histological features of cryofibrinogenemia can confirm the presence of cryofibrinogen within small and medium arteries, plus occlusive thrombotic diathesis composed of eosinophilic refractile deposits within vessel lumina. Cryofibrinogenemia is a treatable and potentially reversible disease.In moderate forms, it can be treated by simply avoiding cold temperatures. The use of corticosteroids in association with low-dose aspirin is the treatment of choice for moderate forms, although stanozolol is an alternative maintenance therapy. Immunosuppressive therapies, plasmapheresis, and/or intravenous fibrinolysis are useful at treating severe forms of cryofibrinogenemia. The use of anticoagulants is limited to the management of thrombotic events. Treatment of secondary cryofibrinogenemia involves the management of associated diseases. Regular follow-ups are needed because of the high risk of recurrence. Moreover, up to half of patients with cryofibrinogenemia considered as essential may develop lymphomas in the following years. Compared with cryoglobulinemia, less is known about cryofibrinogenemia. Its diagnosis should be considered when suggestive clinical manifestations are present and when there are specific biopsy findings. Although identification of cryofibrinogen in blood samples is simple and inexpensive, cryofibrinogenemia can be asymptomatic, and a lack of diagnosis criteria can make diagnosis difficult to confirm. This review describes the clinical manifestations and the biological and pathological features and discusses the criteria used to diagnose and manage cryofibrinogenemia.


Assuntos
Crioglobulinemia/diagnóstico , Crioglobulinemia/patologia , Gerenciamento Clínico , Corticosteroides/uso terapêutico , Adulto , Temperatura Baixa/efeitos adversos , Crioglobulinemia/sangue , Crioglobulinas/metabolismo , Feminino , Fibrinogênios Anormais/metabolismo , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Plasmaferese
10.
Crit Care Med ; 40(1): 104-11, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21926591

RESUMO

OBJECTIVE: To assess the efficacy and safety of rituximab in adults responding poorly to standard treatment for severe autoimmune thrombotic thrombocytopenic purpura. DESIGN: Open-label prospective study. Outcomes in the survivors were compared to those of 53 historical survivors who were given therapeutic plasma exchange alone or with vincristine. SETTING: Hospitals belonging to the Reference Network for Thrombotic Microangiopathies in France. PATIENTS: Twenty-two adults with either no response or a disease exacerbation when treated with intensive therapeutic plasma exchange. INTERVENTION: Add-on rituximab therapy, four infusions over 15 days. MEASUREMENTS AND MAIN RESULTS: One patient died despite two rituximab infusions. In the rituximab-treated patients, the time to a durable remission was significantly shortened (p = .03), although the plasma volume required to achieve a durable remission was not significantly different compared to the controls. Platelet count recovery occurred within 35 days in all 21 survivors, compared to only 78% of the historical controls (p < .02). Of the rituximab-treated patients, none had a relapse within the first year but three relapsed later on. In patients treated with rituximab, a rapid and profound peripheral B-cell depletion was produced, lasting for 9 months and correlating with higher a disintegrin and metalloproteinase with thrombospondin-13 activity and lower anti-a disintegrin and metalloproteinase with thrombospondin-13 antibody titers. These differences were no longer significant after 12 months. No severe side effects occurred. CONCLUSIONS: Adults with severe thrombocytopenic purpura who responded poorly to therapeutic plasma exchange and who were treated with rituximab had shorter overall treatment duration and reduced 1-yr relapses than historical controls.


Assuntos
Anticorpos Monoclonais Murinos/uso terapêutico , Fatores Imunológicos/uso terapêutico , Troca Plasmática , Púrpura Trombocitopênica Trombótica/tratamento farmacológico , Adulto , Feminino , Humanos , Masculino , Rituximab , Terapia de Salvação , Falha de Tratamento , Resultado do Tratamento
11.
Rheumatology (Oxford) ; 51(3): 460-7, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22087012

RESUMO

OBJECTIVE: Scleroderma renal crisis (SRC) is a severe manifestation of SSc, whose prognosis remains severe, despite treatment with angiotensin-converting-enzyme inhibitor and dialysis. This study was undertaken to describe SRC characteristics, prognosis and outcome, and evaluate the responsibility of CSs in its occurrence. METHODS: Analysis concerned 91 SSc patients with SRC who were compared with 427 non-SRC-SSc patients taken as controls. RESULTS: Among the 91 SRC patients, 71 (78.0%) had high blood pressure, 53 (58.2%) hypertensive encephalopathy and 51 (56.0%) thrombotic microangiopathy; 64 (70.3%) had received CSs before or concomitantly with SRC vs 156 (36.5%) non-SRC-SSc patients (P < 0.001). Treated SRC patients also received more prednisone 29.3 (28.4) vs 3.6 (9.9) mg than controls (P < 0.001). SRC clinical outcomes were poor: 49 (53.8%) patients required dialysis, which was definitive for 38. Thirty-seven (40.7%) SRC patients died vs 10.8% of the controls (P < 0.001). Death was most frequent among dialysed patients who never recovered renal function (22 vs 2) and 13 never-dialysed SRC patients died. CONCLUSIONS: Although SRC prognosis has improved markedly, SRC remains a severe manifestation of SSc, despite treatment with angiotensin-converting enzyme inhibitor and dialysis. CSs contributed significantly to SRC occurrence.


Assuntos
Injúria Renal Aguda/etiologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Glucocorticoides/uso terapêutico , Prednisona/uso terapêutico , Diálise Renal , Escleroderma Sistêmico/complicações , Injúria Renal Aguda/mortalidade , Injúria Renal Aguda/terapia , Adulto , Idoso , Estudos de Casos e Controles , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Escleroderma Sistêmico/mortalidade , Escleroderma Sistêmico/terapia , Taxa de Sobrevida , Resultado do Tratamento
12.
Haematologica ; 97(8): 1181-6, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22580997

RESUMO

BACKGROUND: Acquired thrombotic thrombocytopenic purpura is still associated with a 10-20% death rate. It has still not been possible to clearly identify early prognostic factors of death. This study involved thrombotic thrombocytopenic purpura patients with acquired severe (<10% of normal activity) ADAMTS13 deficiency and aimed to identify prognostic factors associated with 30-day death. DESIGN AND METHODS: The study involved a prospective cohort of patients and was carried out between October 2000 and August 2010. A validation cohort of patients was set up from September 2010 to August 2011. Altogether, 281 (analysis cohort) and 66 (validation cohort) consecutive adult thrombotic thrombocytopenic purpura patients with acquired severe ADAMTS13 deficiency were enrolled. The study evaluated 30-day mortality after treatment initiation according to characteristics at inclusion. RESULTS: Non-survivors (11%) were older (P=10(-6)) and more frequently presented arterial hypertension (P=5.10(-4)) and ischemic heart disease (P=0.013). Prognosis was increasingly poor with age (P=0.004). On presentation, cerebral manifestations were more frequent in non-survivors (P=0.018) and serum creatinine level was higher (P=0.008). The most significant independent variables determining death were age, severe cerebral involvement and LDH level 10 N or over. A 3-level risk score for early death was defined and confirmed in the validation cohort using these variables, with higher values corresponding to increased risk of early death. CONCLUSIONS: A risk score for early death was defined in patients with thrombotic thrombocytopenic purpura and validated on an independent cohort. This score should help to stratify early treatment and identify patients with a worse prognosis.


Assuntos
Proteínas ADAM/deficiência , Modelos Estatísticos , Púrpura Trombocitopênica Idiopática/mortalidade , Proteína ADAMTS13 , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Púrpura Trombocitopênica Idiopática/etiologia , Curva ROC , Sistema de Registros , Reprodutibilidade dos Testes
13.
Transfusion ; 52(11): 2436-44, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22404639

RESUMO

BACKGROUND: The objective was to assess the efficacy and safety of splenectomy and cyclophosphamide as salvage therapies in severe thrombotic thrombocytopenic purpura (TTP). STUDY DESIGN AND METHODS: During a 10-year period, patients who did not improve with plasma exchanges, steroids, vincristine, and/or rituximab were considered for splenectomy or cyclophosphamide. Patients with a documented severe (<10% of normal value) acquired ADAMTS13 deficiency are reported here. RESULTS: Eighteen patients with a severe acquired ADAMTS13 deficiency required a salvage therapy. Thirteen patients had a splenectomy 19 (interquartile range [IQR], 10-51) days after TTP diagnosis. One patient died the day after splenectomy. The remaining patients improved platelets (PLTs) until Day 6, along with a rapid and major lactate dehydrogenase improvement. Six patients, however, subsequently experienced a transient worsening. Durable PLT count recovery in survivors was observed within 13 (IQR, 11.5-25.5) days. Postoperative complications included thromboembolic events (two cases) and infections (five cases). Five patients received pulses of cyclophosphamide 12 (IQR, 12-15) days after TTP diagnosis. All patients recovered PLTs 10 (IQR, 9-24) days after the first pulse and two experienced a transient worsening. Three patients experienced infections. Three relapses occurred 5 months, 2.5 years, and 4.5 years after splenectomy and one relapse occurred 3.5 years after cyclophosphamide. After a 2.5 (IQR, 0.75-6.2)-year follow-up, the overall survival was 94%. CONCLUSION: Cyclophosphamide and splenectomy provide comparable high remission rates in severe TTP with acceptable side effects and should be considered in the more severe patients who do not improve with other therapies.


Assuntos
Ciclofosfamida/administração & dosagem , Púrpura Trombocitopênica Trombótica/tratamento farmacológico , Púrpura Trombocitopênica Trombótica/mortalidade , Terapia de Salvação/métodos , Esplenectomia/métodos , Adulto , Ciclofosfamida/efeitos adversos , Feminino , Seguimentos , França/epidemiologia , Humanos , Masculino , Agonistas Mieloablativos/administração & dosagem , Agonistas Mieloablativos/efeitos adversos , Pulsoterapia , Sistema de Registros/estatística & dados numéricos , Indução de Remissão , Índice de Gravidade de Doença , Resultado do Tratamento
14.
Nephrol Dial Transplant ; 26(12): 3930-7, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21459784

RESUMO

BACKGROUND: Henoch-Schönlein purpura (HSP) and IgA nephropathy (IgAN) are characterized by mesangial deposition of polyclonal IgA eventually showing aberrant glycosylation, affinity for mesangial cells and/or co-precipitation with antigen, bacterial peptides, autoantibodies or soluble receptors. IgA were also suggested to be negatively charged and predominantly of λ type but rarely in a monoclonal form. METHODS: A gammopathy case with HSP provided us with a unique molecularly defined nephritogenic IgA1λ. Immunological analysis, biological activities, glycosylation analysis and finally IgA sequence were determined. RESULTS: Compared to IgA1 from healthy subjects or IgAN patients, IgA1 CAT showed hyposialylation but no hypogalactosylation, in agreement with underexpression of sialyltransferase genes by the plasma cell clone. IgA variable domains had low pIs with negatively charged complementarity-determining regions. Weak reactivity appeared against the cationic autoantigen lactoferrin, which was, however, absent from kidney deposits. Deposition also occurred in mice upon injection of only the polymeric form of IgA1 CAT, despite whether or not co-injected with lactoferrin. CONCLUSIONS: This monoclonal model of IgA nephritogenicity strongly suggests that beside hinge region glycosylation, V domains play a role in IgA stability and pathogenicity and supports the hypothesis that responses against cationic epitopes from pathogens or autoantigens may select negatively charged complementarity-determining regions prone either to bind charged structures of the mesangium or to promote by themselves IgA aggregation and deposition.


Assuntos
Mesângio Glomerular , Glomerulonefrite por IGA/imunologia , Imunoglobulina A , Paraproteinemias/imunologia , Idoso , Feminino , Glomerulonefrite por IGA/complicações , Humanos , Vasculite por IgA/complicações
15.
Pharmacoepidemiol Drug Saf ; 20(7): 747-53, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21438068

RESUMO

PURPOSE: Life-threatening hyperkalemia may be induced by drugs and preventable in at-risk patients. This study was designed to describe cases of 'serious' drug-associated hyperkalemia. METHODS: Adult subjects with a serum potassium concentration above 6.5 mmol/L detected at admission or during hospital stay in nephrology, cardiology, geriatric, emergency or intensive care units were identified by biology laboratories of hospitals and clinics located in Midi-Pyrenees (southwest France). Patients dialyzed for end-stage kidney disease were excluded. Data were collected from medical files. Hyperkalemia was defined as drug-associated if at least one drug known to increase serum potassium concentration was taken when hyperkalemia occurred (among drugs taken in outpatient care for hyperkalemia detected at admission and among drugs taken in outpatient care and continued at hospital and drugs introduced from admission for hyperkalemia detected during hospital stay). RESULTS: Of 168 hyperkalemia cases, 102 (60.7%) were classified as drug-associated. They concerned elderly patients (mean age: 76.1 years) often having arterial hypertension and/or cardiac diseases (88.2%). Risk factors, mainly acute kidney failure, were observed in almost all cases (98.0%). Drugs predominantly involved were angiotensin-converting enzyme inhibitors (47.1%), spironolactone (41.2%), angiotensin II receptor antagonists (23.5%) and potassium supplements (23.5%). In 10% of cases, death could be attributed to hyperkalemia. CONCLUSIONS: Laboratory databases allowed an exhaustive identification of hyperkalemia cases. The frequency of drug-related hyperkalemia and their characteristics suggest that treatment with drugs known to increase serum potassium concentration can be inappropriate, especially regarding associations or indications, and is highly risky for predisposed patients.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Hiperpotassemia/induzido quimicamente , Potássio/sangue , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais/estatística & dados numéricos , Feminino , França , Hospitalização/estatística & dados numéricos , Humanos , Hiperpotassemia/etiologia , Hiperpotassemia/fisiopatologia , Masculino , Pessoa de Meia-Idade , Preparações Farmacêuticas/administração & dosagem , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença
16.
Nephrol Ther ; 5(4): 292-8, 2009 Jul.
Artigo em Francês | MEDLINE | ID: mdl-19357010

RESUMO

We report seven cases of patients treated with fluindione, who presented with acute renal failure, associated with clinical features of allergy: poor status, fever, dyspnea, lymphadenopathy and erythroderma. All patients had elevated eosinophil counts. Renal biopsy disclosed in all cases a tubulo-interstitial nephritis with or without granuloma. The responsibility of fluindione, an oral anticoagulant widely used in France could be demonstrated. To our knowledge, there are only three reports of single cases of acute renal failure related to fluindione published so far to date. This serious side effect of fluindione should be recognized.


Assuntos
Injúria Renal Aguda/induzido quimicamente , Anticoagulantes/efeitos adversos , Nefrite Intersticial/imunologia , Nefrite Intersticial/patologia , Fenindiona/análogos & derivados , Idoso , Idoso de 80 Anos ou mais , Hipersensibilidade a Drogas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nefrite Intersticial/induzido quimicamente , Fenindiona/efeitos adversos
17.
Rev Prat ; 58(5): 499-506, 2008 Mar 15.
Artigo em Francês | MEDLINE | ID: mdl-18524106

RESUMO

Renal involvement occurs in 75% of the patients with systemic necrotizing small-vessel vasculitis ie microscopic polyangiitis, Wegener's granulomatosis or Churg-Strauss syndrome. Small-vessel vasculitis may also be limited to the kidney. The hallmark of small-vessel pauci-immune vasculitides consists of necrotizing glomerulonephritis and resultant crescent formation, without immune-complex deposits in vessel walls. The resulting renal manifestations consist of haematuria, proteinuria and rapidly progressive renal failure. ANCA testing has a 90% sensitivity for renal-associated pauci-immune small-vessel vasculitis. Kidney biopsy is required for demonstrating necrotizing vasculitis. Early identification and prompt treatment are mandatory to avoid early mortality and end-stage renal failure. Induction therapy combines corticosteroids and IV cyclophosphamide. Plasma exchange in indicated in the patients presenting with active renal lesions and serum creatinine > 500 micromol/L. Maintenance of immunosuppressive therapy is required for 18 months. Twenty to 50% of the patients relapse during follow-up, and close monitoring is warranted for early detection.


Assuntos
Síndrome de Churg-Strauss/diagnóstico , Glomerulonefrite/diagnóstico , Granulomatose com Poliangiite/diagnóstico , Rim/patologia , Vasculite/diagnóstico , Corticosteroides/administração & dosagem , Corticosteroides/uso terapêutico , Biópsia , Síndrome de Churg-Strauss/patologia , Ciclofosfamida/administração & dosagem , Ciclofosfamida/uso terapêutico , Diagnóstico Diferencial , Quimioterapia Combinada , Seguimentos , Glomerulonefrite/etiologia , Glomerulonefrite/patologia , Granulomatose com Poliangiite/patologia , Hematúria/diagnóstico , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/uso terapêutico , Estudos Multicêntricos como Assunto , Troca Plasmática , Prognóstico , Proteinúria/diagnóstico , Recidiva , Insuficiência Renal/etiologia , Insuficiência Renal/patologia , Insuficiência Renal/terapia , Fatores de Tempo , Vasculite/patologia
18.
Ann N Y Acad Sci ; 1108: 41-50, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17893969

RESUMO

The objective of the study was to investigate the influence of the blood concentrations of hydroxychloroquine ([HCQ]) and its derivative desethylhydroxychloroquine ([DHCQ]) on lymphocyte activation or differentiation in HCQ-treated lupus patients. We studied the correlations between [HCQ], [DHCQ], and the frequency of various lymphocyte subsets in 58 HCQ-treated lupus patients (mean HCQ dose: 4.93 +/- 1.58 mg/kg/day; mean duration of the disease: 122 +/- 64 months). [HCQ] and [DHCQ] were determined by high-performance liquid chromatography (HPLC). Lymphocyte markers were studied by flow cytometry using monoclonal anti-CD3, -CD4, -CD8, -CD25, -DR, -CD45RA, -CD45RO, -CD19, -CD38, and -CD86 antibodies. sIL2-R serum concentrations were measured by enzyme-linked immunosorbent assay (ELISA). [HCQ] and [DHCQ] were 599.9 ng/mL (median: 529.5; range: 55-1935) and 353.43 (median: 286 ng/mL; range: 118-1090). In a multiple regression analysis, [HCQ] and [DHCQ] were associated with the HCQ prescribed dose in mg/kg/day (P = 0.0002 and P = 0.03) and with compliance to the treatment (P = 0.004 and P = 0.03). We found a negative correlation between [HCQ], [DHCQ], and the CD45RO+ cell frequency among CD3+CD4+ cells (P = 0.03 and P = 0.007, respectively). Other lymphocyte subset markers (LSMs) and sIL2-R concentrations were not significantly associated with [HCQ] or [DHCQ]. In the multiple regression analysis, CD45RO+ expression was negatively influenced by [HCQ] (P = 0.005), and positively influenced by smoking habits (P = 0.005) and age (P = 0.005). Similar results were found in the multivariate model including [DHCQ]. Disease activity and taking more than 10 mg/day of corticosteroids or an immunosuppressive drug did not influence CD45RO+ expression. Lupus patients had less CD3+CD4+CD45RO+ cells than controls (P = 0.03). In lupus patients, HCQ and DHCQ may alter the generation or the blood circulation of CD4+CD45RO+ lymphocytes in a concentration-dependent pattern.


Assuntos
Antirreumáticos/sangue , Linfócitos T CD4-Positivos/efeitos dos fármacos , Hidroxicloroquina/análogos & derivados , Hidroxicloroquina/sangue , Lúpus Eritematoso Sistêmico/sangue , Subpopulações de Linfócitos T/efeitos dos fármacos , Adulto , Antirreumáticos/metabolismo , Antirreumáticos/uso terapêutico , Linfócitos T CD4-Positivos/citologia , Diferenciação Celular/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Relação Dose-Resposta a Droga , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Humanos , Hidroxicloroquina/metabolismo , Hidroxicloroquina/uso terapêutico , Antígenos Comuns de Leucócito , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Ativação Linfocitária/efeitos dos fármacos , Masculino , Subpopulações de Linfócitos T/citologia
19.
PLoS One ; 11(3): e0151696, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27002825

RESUMO

OBJECTIVE: To investigate association between genetic polymorphisms of GST, CYP and renal outcome or occurrence of adverse drug reactions (ADRs) in lupus nephritis (LN) treated with cyclophosphamide (CYC). CYC, as a pro-drug, requires bioactivation through multiple hepatic cytochrome P450s and glutathione S transferases (GST). METHODS: We carried out a multicentric retrospective study including 70 patients with proliferative LN treated with CYC. Patients were genotyped for polymorphisms of the CYP2B6, CYP2C19, GSTP1, GSTM1 and GSTT1 genes. Complete remission (CR) was defined as proteinuria ≤0.33g/day and serum creatinine ≤124 µmol/l. Partial remission (PR) was defined as proteinuria ≤1.5g/day with a 50% decrease of the baseline proteinuria value and serum creatinine no greater than 25% above baseline. RESULTS: Most patients were women (84%) and 77% were Caucasian. The mean age at LN diagnosis was 41 ± 10 years. The frequency of patients carrying the GST null genotype GSTT1-, GSTM1-, and the Ile→105Val GSTP1 genotype were respectively 38%, 60% and 44%. In multivariate analysis, the Ile→105Val GSTP1 genotype was an independent factor of poor renal outcome (achievement of CR or PR) (OR = 5.01 95% CI [1.02-24.51]) and the sole factor that influenced occurrence of ADRs was the GSTM1 null genotype (OR = 3.34 95% CI [1.064-10.58]). No association between polymorphisms of cytochrome P450s gene and efficacy or ADRs was observed. CONCLUSION: This study suggests that GST polymorphisms highly impact renal outcome and occurrence of ADRs related to CYC in LN patients.


Assuntos
Ciclofosfamida/uso terapêutico , Glutationa S-Transferase pi/genética , Glutationa Transferase/genética , Imunossupressores/uso terapêutico , Nefrite Lúpica/genética , Adulto , Creatinina/sangue , Citocromo P-450 CYP2B6/genética , Citocromo P-450 CYP2C19/genética , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/genética , Feminino , Frequência do Gene/genética , Estudos de Associação Genética , Humanos , Nefrite Lúpica/tratamento farmacológico , Nefrite Lúpica/enzimologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Proteinúria/urina , Estudos Retrospectivos , Adulto Jovem
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