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1.
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
2.
BMC Nephrol ; 19(1): 3, 2018 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-29310591

RESUMO

BACKGROUND: Kidney transplantation following uncontrolled donation after circulatory death (uDCD) presents a high risk of delayed graft function due to prolonged warm ischemia time. In order to minimise the effects of ischemia/reperfusion injury during warm ischemia, normothermic recirculation recently replaced in situ perfusion prior to implantation in several institutions. The aim of this study was to compare these preservation methods on kidney graft outcomes. METHODS: The primary endpoint was the one-year measured graft filtration rate (mGFR). We collected retrospective data from 64 consecutive uDCD recipients transplanted over a seven-year period in a single centre. RESULTS: Thirty-two grafts were preserved by in situ perfusion and 32 by normothermic recirculation. The mean ± SD mGFR at 1 year post-transplantation was 43.0 ± 12.8 mL/min/1.73 m2 in the in situ perfusion group and 53.2 ± 12.8 mL/min/1.73 m2 in the normothermic recirculation group (p = 0.01). Estimated GFR levels were significantly higher in the normothermic recirculation group at 12 months (p = 0.01) and 24 months (p = 0.03) of follow-up. We did not find any difference between groups regarding patient and graft survival, delayed graft function, graft rejection, or interstitial fibrosis. CONCLUSIONS: Function of grafts preserved by normothermic recirculation was better at 1 year and the results suggest that this persists at 2 years, although no difference was found in short-term outcomes. Despite the retrospective design, this study provides an additional argument in favour of normothermic recirculation.


Assuntos
Sobrevivência de Enxerto/fisiologia , Parada Cardíaca/diagnóstico , Parada Cardíaca/fisiopatologia , Transplante de Rim/métodos , Preservação de Órgãos/métodos , Doadores de Tecidos , Adulto , Função Retardada do Enxerto/diagnóstico , Função Retardada do Enxerto/fisiopatologia , Feminino , Seguimentos , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/fisiopatologia , Rejeição de Enxerto/prevenção & controle , Humanos , Transplante de Rim/tendências , Masculino , Pessoa de Meia-Idade , Preservação de Órgãos/normas , Estudos Retrospectivos , Choque/diagnóstico , Choque/fisiopatologia , Resultado do Tratamento
3.
Transpl Int ; 30(12): 1284-1291, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28805266

RESUMO

Kidneys from uncontrolled donors after cardiac arrest (uDCD) suffer from a period of warm ischemia between cardiac arrest and cold flushing. Aim of the study was to evaluate renal outcomes of uDCD kidneys selected on the basis of renal Resistance Index (RI) and its influence on graft function and survival. The study included 44 kidneys procured from 26 uDCD starting 1.1.2006 until 12.31.2013. The donors (Maastricht category II) underwent cardiopulmonary resuscitation by assisted ventilation and chest compression; the organs were preserved with in situ cold perfusion or a normothermic regional perfusion. All kidneys were perfused on hypothermic (1-4 °C) pulsatile perfusion machine (RM3; Waters Medical System) and discarded when RI ≥0.5 mmHg/ml/min after 6 h of perfusion. There was one (2.2%) primary non function, while 37 recipients (84.1%) experienced delayed graft function. Graft survival was 97.6% at 1 and 3 post-transplantation years. Linear regression models showed that lower values of RI at the end of perfusion were associated with higher values of Modification of Diet in Renal Disease at 3 (P = 0.049) and 6 months after transplantation (P = 0.010) and with higher values of inulin clearance at 1 year (P = 0.030). RI showed to be a useful tool to select uDCD kidneys allowing to achieve good clinical results.


Assuntos
Oxigenação por Membrana Extracorpórea , Parada Cardíaca , Transplante de Rim/métodos , Preservação de Órgãos/métodos , Isquemia Quente/métodos , Estudos de Coortes , Feminino , Seguimentos , Rejeição de Enxerto , Sobrevivência de Enxerto , Humanos , Transplante de Rim/efeitos adversos , Modelos Lineares , Masculino , Estudos Retrospectivos , Medição de Risco , Estatísticas não Paramétricas , Fatores de Tempo , Obtenção de Tecidos e Órgãos/métodos , Resultado do Tratamento
4.
Kidney Int ; 88(6): 1374-1382, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26266834

RESUMO

Reducing immunosuppression has been proposed as a means of preventing cancer in kidney transplant recipients but this can precipitate graft rejection. Here we tested whether anti-tumor natural killer (NK) cell and allo-responsive T-cell function in kidney transplant recipients may predict cancer risk and define risk of rejection. NK cell function was measured by the release of lactate dehydrogenase and T-cell allo-response by interferon-γ quantification using a panel of reactive T-cell enzyme-linked immunospot (ELISPOT) in 56 kidney transplant recipients with current or past cancer and 26 kidney transplant recipients without cancer. NK function was significantly impaired and the allo-response was significantly lower in kidney transplant recipients with cancer. With prospective follow-up, kidney transplant recipients with poor NK cell function had a hazard ratio of 2.1 (95% confidence interval 0.97-5.00) for the combined end point of metastatic cancer, cancer-related death, or septic death. Kidney transplant recipients with low interferon-γ release were also more likely to reach this combined end point. Thus, posttransplant monitoring of allo-immunity and NK cell function is useful for assessing the risk of over immunosuppression for the development of malignancy and/or death from cancer or sepsis.

5.
Nephrology (Carlton) ; 19(7): 420-5, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24802649

RESUMO

AIM: One of the factors that may affect survival and function of kidney graft is its functional mass. METHODS: In a prospective study, we investigated the impact of the ratio between donor kidney weight in grams and recipient bodyweight in kilograms (DKW/RBW) on creatinine clearance, inulin clearance, and proteinuria: 154 kidneys from deceased donors were weighed and the mean kidney weight was 227 ± 59 g, the bodyweight of the recipients was 64 ± 19 kg. RESULTS: This study showed significant lower values of modification of diet in renal disease (MDRD) in patients with DKW/RBW ratio 2.5 g/kg and between 2.5 and 4.5 g/kg compared with those with DKW/RBW ratio >4.5 g/kg as well as in patients with DKW/RBW ratio <3 g/kg and between 3 and 4 g/kg compared with those with DKW/RBW ratio >4 g/kg; moreover a random coefficient model showed a different time evolution in creatinine clearance values in patients with DKW/RBW ≤ 3 g/kg when compared with patients with DKW/RBW ratio >4 g/kg. There were significant lower values of inulin clearance in patients with DKW/RBW ratio between 2.5 and 4.5 g/kg compared with those with DKW/RBW ratio >4.5 g/kg at 12 post-transplant months and a significantly greater occurrence and earlier appearance of proteinuria in the recipients with DKW/RBW ratio <2.5 g/kg. DKW/RBW ratio did not influence DGF incidence and graft survival. Donor and recipient gender, number of acute rejection episodes and donor age also significantly influenced MDRD values. CONCLUSIONS: Measurements of graft weight as well as donor kidney and recipient body matching should be recommended as influencing renal function.


Assuntos
Peso Corporal/fisiologia , Sobrevivência de Enxerto/fisiologia , Transplante de Rim , Rim/patologia , Tamanho do Órgão/fisiologia , Transplantes , Adulto , Biópsia/métodos , Creatinina/análise , Feminino , Humanos , Itália , Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Transplante de Rim/métodos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados da Assistência ao Paciente , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/patologia , Complicações Pós-Operatórias/prevenção & controle , Proteinúria/etiologia , Proteinúria/patologia , Proteinúria/prevenção & controle , Transplantados , Transplantes/patologia , Transplantes/fisiopatologia
6.
Int J Urol ; 21(2): 204-6, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23944687

RESUMO

Organ shortage is a major problem in organ transplantation. For this reason, transplantation teams have found it necessary to revisit their organ acceptance criteria. Uncontrolled deceased donors after cardiac arrest could increase the donor pool by 20%, but at the same time there is a greater risk of delayed graft function and primary non-function. Dual kidney transplantation is an option when single kidney transplantation cannot be carried out because of lack of organ quality. We report for the first time our four first dual kidney transplantation from uncontrolled deceased donors after cardiac arrest with a follow up longer than 1 year. We described graft outcomes until 5 years, and histology at 3 and 12 months after transplantation. All organs were machine perfused in order to assess their quality leading to a single kidney transplantation or dual kidney transplantation decision. After 1 year of follow up, all grafts were functional with a mean estimated glomerular filtration rate of 44.5 ± 3.3 mL/min/1.73 m(2), and a mean inulin clearance of 43.7 ± 13.6 mL/mn/1.73 m(2). These findings suggest that dual kidney transplantation can represent a viable option for kidneys unsuitable for single kidney transplantation without increasing the rate of surgical complications. Successful transplantation is linked to histological, biological and donor clinical criteria, as well as perfusion parameters.


Assuntos
Sobrevivência de Enxerto , Parada Cardíaca , Transplante de Rim/métodos , Rim/fisiologia , Doadores de Tecidos , Adulto , Cadáver , Seguimentos , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Perfusão , Estudos Retrospectivos , Obtenção de Tecidos e Órgãos/métodos , Resultado do Tratamento
7.
Transpl Immunol ; 20(4): 209-11, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19166936

RESUMO

We report the case of a renal transplanted patient, in whom the detection of a unique anti HLA-DP antibody response preceded the development of chronic humoral rejection. In addition to donor-specific anti-DP alloantibodies, the patient displayed reactions against several non-donor-specific DP antigens (NDSA). Interestingly, we found that all the DP molecules recognized by the alloantibodies displayed the same amino-acid sequence suggesting that epitope sharing between unrelated HLA molecules was the mechanism underlying NDSA generation. This case highlights the pathogenicity of anti-DP alloantibodies and suggests that it could be more meaningful to match the epitopes than the HLA antigens for the prevention of rejection.


Assuntos
Doença Antimembrana Basal Glomerular/terapia , Formação de Anticorpos , Citotoxicidade Celular Dependente de Anticorpos , Rejeição de Enxerto/imunologia , Antígenos HLA-DP/imunologia , Isoanticorpos/imunologia , Transplante de Rim , Insuficiência Renal/terapia , Adulto , Anemia Hemolítica , Doença Antimembrana Basal Glomerular/imunologia , Doença Antimembrana Basal Glomerular/patologia , Doença Antimembrana Basal Glomerular/fisiopatologia , Epitopos , Feminino , Rejeição de Enxerto/patologia , Humanos , Epitopos Imunodominantes , Memória Imunológica , Isoanticorpos/metabolismo , Gravidez , Insuficiência Renal/imunologia , Insuficiência Renal/patologia , Homologia de Sequência
8.
Nephrol Ther ; 14(3): 167-171, 2018 May.
Artigo em Francês | MEDLINE | ID: mdl-29291940

RESUMO

Buerger's disease or thombo-angiitis obliterans disease is a small vessel's vasculitis, frequently observed in young and smoker's males. Diagnosis is based on both clinical and radiological arguments. There is no specific treatment designed for this disease. We report the case of 43 years old patient presenting with an acute kidney injury associated with Buerger's disease. We reviewed the different case of kidney disease in this rare disease.


Assuntos
Injúria Renal Aguda/complicações , Tromboangiite Obliterante/complicações , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/terapia , Adulto , Angiografia , Diagnóstico Diferencial , Humanos , Rim/irrigação sanguínea , Rim/patologia , Imageamento por Ressonância Magnética , Masculino , Tomografia por Emissão de Pósitrons , Tromboangiite Obliterante/diagnóstico , Tromboangiite Obliterante/terapia
10.
Nephrol Ther ; 12(1): 38-47, 2016 Feb.
Artigo em Francês | MEDLINE | ID: mdl-26563589

RESUMO

Alkali therapy is frequently used during chronic kidney disease and nephrolithiasis: nephrologists and urologists are the key operators. Very few is known about the underlying conditions of such a prescription: the aim of this study was to delineate those determinants. We conducted a prospective survey where French nephrologists and urologists were involved. Responders were without gender distinction and principally nephrologists. Prescription frequency was associated with gender (women), specialty (nephrologists), indications and perceived efficiency. Urologists prescribe more often during nephrolithiasis and nephrologists during chronic kidney disease. Urologists were more expert (by scoring on mineral-based alkaline waters compositions knowledge). By multivariate analysis, prescription frequency is associated with gender (women), indications and perceived efficiency by prescribers, which is itself influenced by feedback from patients. These results could have been influenced by a huge representation of nephrologists but foster physicians to go on listening to feedback from patients, due to a lack of clinical trials on the efficiency of mineral-based alkaline waters in such a field. Finally, physicians' education (especially young nephrologists) on mineral-based alkaline waters should be intensified.


Assuntos
Águas Minerais/administração & dosagem , Nefrologistas/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Prescrições/estatística & dados numéricos , Insuficiência Renal Crônica/terapia , Urologistas/estatística & dados numéricos , Adulto , Feminino , França , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inquéritos e Questionários
11.
J Immunol Res ; 2014: 549315, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24741606

RESUMO

Transplant glomerulopathy (TG) is a major cause of chronic graft dysfunction without effective therapy. Although the histological definition of TG is well characterized, the pathophysiological pathways leading to TG development are still poorly understood. Electron microscopy suggests an earlier appearance of TG and suggests that endothelial cell injury is the first sign of the disease. The pathogenic role of human leukocyte antigen (HLA) antibodies in endothelial cells has been described in acute vascular and humoral rejection. However the mechanisms and pathways of endothelial cell injury by HLA antibodies remain unclear. Despite the description of different causes of the morphological lesion of TG (hepatitis, thrombotic microangiopathy), the strong link between TG and chronic antibody mediated rejection suggests a major role for HLA antibodies in TG formation. In this review, we describe the effect of classes I or II HLA-antibodies in TG and especially the implication of donor specific antibodies (DSA). We update recent studies about endothelial cells and try to explain the different signals and intracellular pathways involved in the progression of TG.


Assuntos
Glomerulonefrite/imunologia , Glomerulonefrite/patologia , Transplantes/imunologia , Transplantes/patologia , Especificidade de Anticorpos/imunologia , Autoanticorpos/imunologia , Complemento C4/imunologia , Endotélio/imunologia , Endotélio/patologia , Glomerulonefrite/terapia , Antígenos HLA/imunologia , Humanos , Avaliação de Resultados da Assistência ao Paciente , Fatores de Risco
12.
Nephrol Ther ; 9(3): 137-42, 2013 Jun.
Artigo em Francês | MEDLINE | ID: mdl-23434289

RESUMO

The arterio-venous fistula (AVF) is the most common vascular access to perform hemodialysis (HD). The HD venous central catheter use should only be proposed to old patients and/or patients without vascular access construction feasibility. These HD catheters are often responsible of infectious and thrombosis complications. We performed, for the first time in French Polynesia, a retrospective study based on 214 patients receiving 618 HD catheters, to evaluate the infectious complication rate due to HD catheters. We showed that 17.4% of HD catheters present with infection. The number of bacteraemia due to HD catheters is 2.57/1000 days-catheters and the number of infection due to HD catheter is 1.43/1000 days-catheters. Eighteen percent of patients requiring an emergency HD without AVF access are transferred in intensive care unit due to infectious HD catheter complications. We observed a similar bacteriological environment than in literature. However, the number of tunneled HD catheter is really lower to that of the number required in European recommendations and we observed an abnormal number of non-functional AVF 1 month after creation. These results involve our nephrology unit to increase the number of tunneled catheters to limit the infectious risk and also to fit with the best practices guidelines.


Assuntos
Bacteriemia/epidemiologia , Infecções Relacionadas a Cateter/epidemiologia , Cateteres de Demora/efeitos adversos , Soluções para Hemodiálise/efeitos adversos , Diálise Renal/instrumentação , Adulto , Idoso , Cateterismo Venoso Central , Feminino , França/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Polinésia/epidemiologia , Estudos Retrospectivos
13.
Nephrol Ther ; 7(3): 188-90, 2011 Jun.
Artigo em Francês | MEDLINE | ID: mdl-21296633

RESUMO

We followed a 60-year-old woman in our department for a vascular chronic kidney disease. The peritoneal dialysis was stopped because of a Candida albicans catheter infection. As the patient refused the arterio-venous fistula creation, we have placed a central venous catheter (Medcomp 32cm). Because the instability of the cuff, we decided to remove and change it by another one (Quinton 40cm). The discovery of an important cylindrical calcification has complicated the manipulation requiring tranquility and agility. The finding of a massive calcification is uncommon and confirms the major risk of calcification in chronic kidney disease patients.


Assuntos
Calcinose/etiologia , Cateterismo Venoso Central/efeitos adversos , Falência Renal Crônica/terapia , Diálise Renal , Feminino , Humanos , Pessoa de Meia-Idade
14.
Nephrol Ther ; 7(6): 457-66, 2011 Nov.
Artigo em Francês | MEDLINE | ID: mdl-21515102

RESUMO

Renal failure, mostly related to myeloma cast nephropathy (MCN), is a frequent complication of multiple myeloma (MM), which occurs in up to 50% of patients during the course of the disease. Persistent renal failure in MM is associated with poor survival. Treatment of MCN relies on urgent symptomatic measures (alkalinisation, rehydration, correction of hypercalcemia, and withdrawal of nephrotoxic drugs), with rapid introduction of chemotherapy to efficiently reduce the production of monoclonal light chains (LC). Recent studies suggest that, in patients with MM and severe renal failure due to MCN, rapid removal of circulating LC, through intensive hemodialysis sessions using a new generation high cut-off dialysis membrane, might result in dialysis withdrawal in most patients. If the development of intensive therapy and new efficient chemotherapy agents (thalidomide, bortezomib, lenalidomide) has transformed the care and prognosis of MM, the modalities and safety of these therapeutic regimens in patients with renal failure remain to be defined. The association of bortezomib with dexamethasone should be considered currently as first-line treatment in patients with MM and impaired renal function.


Assuntos
Falência Renal Crônica/etiologia , Mieloma Múltiplo/complicações , Inibidores da Angiogênese/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ácidos Borônicos/administração & dosagem , Ácidos Borônicos/uso terapêutico , Bortezomib , Ensaios Clínicos como Assunto , Contraindicações , Ciclofosfamida/administração & dosagem , Dexametasona/administração & dosagem , Hidratação , Humanos , Hipercalcemia/tratamento farmacológico , Hipercalcemia/etiologia , Cadeias Leves de Imunoglobulina/metabolismo , Falência Renal Crônica/metabolismo , Falência Renal Crônica/terapia , Lenalidomida , Melfalan/administração & dosagem , Estudos Multicêntricos como Assunto , Mieloma Múltiplo/fisiopatologia , Mieloma Múltiplo/terapia , Proteínas do Mieloma/metabolismo , Estudos Prospectivos , Inibidores de Proteases/uso terapêutico , Pirazinas/administração & dosagem , Pirazinas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Diálise Renal , Talidomida/análogos & derivados , Talidomida/uso terapêutico
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