La transplantation d’organe est aujourd’hui largement utilisée dans les cas de défaillance terminale d’organe solide. Les nombreuses avancées techniques concernant la conservation des organes, la chirurgie et les suites opératoires, le développement de la prévention, du diagnostic et du traitement des rejets et des infections ont contribué à l’augmentation de la survie du greffon et des patients. La transplantation a pris un essor très important depuis l’instauration de traitements immunosuppresseurs de plus en plus efficaces et ayant des effets ciblés sur les mécanismes immunitaires d’activation lymphocytaire mis en jeu lors des réactions de rejet de greffon. Mais l’utilisation de ces traitements limitant les rejets favorise le développement d’infections et de cancers.Les réactions de rejets de greffon mettent en jeu des alloantigènes du donneur, contre lesquels le receveur développera des réponses immunitaires humorales et cellulaires délétères. Ces réactions vont entraîner des lésions au sein du tissu greffé ayant des conséquences à court et long terme pour la fonction de l’organe. Les infections virales, et le cytomégalovirus (CMV) tout particulièrement, vont également générer des réponses inflammatoires et cytotoxiques in situ, également délétères et favorisant les réactions allogéniques. Les interactions entre réactions immunologiques de rejet et réactions antivirales sont complexes et font intervenir différents acteurs et mécanismes de la réponse immunitaire. De plus, les infections virales, de par la mémoire immunitaire spécifique, interfèrent également dans la mise en place d’une tolérance du greffon. Dans cet article, nous décrirons les différents mécanismes et intervenants des réactions de rejets de greffon et aborderons leur interaction avec les infections virales.Solid organ transplantation has become a widely utilized and successful modality for treatment of end-stage organ diseases. Improved techniques for organ preservation, surgical procedures and post-surgical monitoring, rejection management, posttransplant infection prophylaxis, diagnostic and treatment have contributed to this success. Most identifiable of the advances in solid organ transplantation is the development of potent immunosuppressive agents, with increasingly precise targets as lymphocyte activation mechanisms. However, the use of these agents in the prevention and management of rejection is closely interrelated to the development of infection and tumour.Graft rejection reactions involved donor allo-antigens, recipients developed deleterious humoral and cellular immune reactions. These reactions will be responsible for tissular damages and had short and long term consequences on organ functions. Inflammatory and cytotoxic reactions against viral infections, particularly CMV infections, are also deleterious for graft tissue and favourable to allogenic immune reactions. Relations between graft rejection and anti-viral reactions are complex and involved immune actors and mechanisms. Viral infections and their specific immune memory also interfere with graft tolerance set up. In this article, graft rejection actors and mechanisms, and their interaction with viral infections will be described.
La prééclampsie est définie par l’association d’une hypertension artérielle gravidique (pression artérielle systolique supérieure ou égale à 140 mm Hg et diastolique supérieure à 90 mm Hg) et d’une protéinurie supérieure ou égale à 300 mg par 24 heures après 20 semaines d’aménorrhée (SA). Elle complique 0,5 à 7 % des grossesses. C’est une pathologie gravidique sévère avec une mortalité et une morbidité fœtale persistante et également des accidents maternels à type d’hématome rétroplacentaire, HELLP syndrome (hemolysis, elevated liver enzymes, low platelets) et éclampsie. Le pronostic vital maternel est engagé en l’absence de traitement qui, une fois la maladie installée, est basé sur l’arrêt de la grossesse et la délivrance du placenta. La corticothérapie doit toujours être privilégiée dans la mesure du possible si le terme le justifie. Le traitement antihypertenseur a pour objectif de limiter les complications maternelles, en particulier neurologiques. Les anticalciques sont de plus en plus utilisés en thérapeutique de première ligne. Le sulfate de magnésium, probablement sous-utilisé en France, doit être prescrit en respectant les règles de prudence et de surveillance. L’objectif est de prévenir les récidives de crises d’éclampsie (prévention secondaire). Dans les prééclampsies sévères et précoces, la prévention primaire est plus contreversée, mais pourrait être réservée aux patientes présentant une excitation pyramidale lorsque le risque convulsif semble imminent. Le traitement préventif chez les femmes à risque, dont l’efficacité réelle reste cependant modérée, est surtout représenté par l’aspirine (100 à 160 mg) en début de grossesse. Ce traitement diminuerait le risque de récidive de prééclampsie de 15 %, la prématurité de 8 % et la mortalité périnatale de 14 %. Ces chiffres sont tout récemment ramenés à 10 % aussi bien pour le risque de récidive de prééclampsie : RR = 0,95 ; 90 % IC (0,84–0,97) que pour la prématurité : RR = 0,95 ; 90 % IC (0,83–0,98). Il n’y aurait, par ailleurs, pas d’action préventive notable sur la mortalité périnatale ni sur les retards de croissance intra-utérin (RCIU). Les sous-groupes à risques comme les greffées rénales, les diabétiques, les HTA chroniques ne bénéficient pas non plus formellement de la réduction de risque de prééclampsie par l’aspirine.Preeclampsia is defined as the association of pregnancy-induced hypertension and proteinuria of 300 mg/24 h or more after 20 weeks gestation. It complicates 0.5 to 7% of pregnancies. It is a severe complication of pregnancy, which leads to persisting fetal morbidity and mortality. It is also responsible for maternal morbidity as placental abruption, HELLP syndrome (hemolysis, elevated liver enzymes, low platelets) and eclampsia. Without treatment, maternal risks are high. Once the disease is confirmed, the treatment consists of ending the pregnancy. Corticosteroids for lung maturity have to be prioritized depending on the term.Antihypertensive drugs are used to limit maternal complications, in particular, in neurological form. Calcium pump inhibitors are increasingly used as a first line choice. Magnesium sulfate, which is probably not used enough in France, needs to be administered with care and strict monitoring. It can be used to prevent a recurrence of eclamptic fits or in the context of early severe preeclampsia with neurological irritability where an eclamptic fit seems imminent. Preventive treatment of preeclampsia consists essentially of low dose aspirin. The efficacy of this treatment is real but moderate. It decreases the risk of recurrence of preeclampsia by 10 to 15%, of prematurity by 8% and of perinatal mortality by 14%. These figures were recently corrected to 10% for the risk of recurrence of preeclampsia: RR = 0.95; 90% CI; (0.84–0.97) and prematurity: RR = 0.95; 90%CI; (0.83–0.98). It seems that it has no significant effect on intra-uterine growth restriction (IUGR) and perinatal death prevention. For the main outcome of preeclampsia, there was no evidence that women in any of subgroups as preexisting renal disease, preexisting diabetes or hypertension benefited more or less from the use of antiplatelet agents than those in any other subgroup.
Background: It is unknown whether kidney transplant patients who receive rabbit antithymocyte globulin (rATG) become immunized against rabbit antibodies, leading to reduced efficacy, or are at higher risk of cytomegalovirus infection or post-transplant lymphoproliferative disorder (FTLD) on retreatment The efficacy and tolerance of rATG when used as induction for the second time in patients undergoing retransplantation have not been evaluated.Methods: In a retrospective case-control study, 54 retransplanted patients who received rATG (Thymoglobulin) induction for the second time during 2004-2010 were compared to a matched cohort of 108 patients receiving rATG induction for a first kidney transplantation during the same period. Maintenance treatment was similar in both groups.Results: Median follow-up was 45.8 months and 47.3 months in the second and first treatment groups, respectively. No differences were observed between the two groups in terms of leukocyte, lymphocyte or platelet depletion. Dose and duration of rATG treatment were similar in both groups, suggesting a similar tolerance profile. Cytomegalovirus infection (including primoinfection and reactivation) occurred in 4/54 retreated patients versus 22/108 controls (p = 0.108). Use of cytomegalovirus prophylaxis was similar between groups. PTLD occurred in one control patient and no retreated patients.Conclusion: A second course of rATG induction results in similar lymphocyte depletion and is as well tolerated as a first course. The incidence of cytomegalovirus infection and post-transplant lymphoproliferative disease was not increased during retreatment Further studies are required to evaluate specific T cell subpopulation depletion and compare long-term outcome in patients receiving a second induction with rATG. (C) 2012 Elsevier B.V. All rights reserved.
A. Brodin‐Sartorius, Y. Mekki, M. Pastural, G. Billaud, S. Daoud, C. Chauvet, J.‐L. Touraine, B. Lina, E. Morelon, O. Thaunat. Severe transfusion‐transmitted parvovirus B19 infection in a naive immunocompromised patient. Transpl Infect Dis 2011: 13: 97–98. All rights reserved.
Introduction. - In the current context of a high incidence end-stage kidney disease and a shortage of organs for kidney transplantation, the increasing use of transplants considered to be "borderline" represents a potential source of transplants. Over the last 10 years, some centers have developed a transplantation strategy, which consists of transplanting two borderline kidneys that cannot be proposed separately in a single recipient. The authors report their experience of dual kidney transplant.Materials and methods. - Since 2001, 15 dual kidney transplants have been performed in a single centre according to a local protocol based on the correspondence between the weight of the donor kidney and the recipient's weight, weighted by the number of fibrotic glomeruli observed on the initial biopsy. In this study, the authors analyze the postoperative complications and functional results observed in patients transplanted according to this protocol.Results. - Dual kidney transplants represented less than 5% of all transplants performed during the study period concerned, which remained tower than the objectives initially announced by the ABM. The surgical technique was left to the surgeon's discretion. The mean follow-up was 26.3 months. Fourteen of the 15 recipients were alive with a functional graft. Surgical complications were globally more frequent when kidneys were transplanted on the same side (versus transplanted on both sides). Mean serum creatinine was 119.4 mol/l. at six months (creatinine clearance according to MDRD formula: 57.3ml/min per 1.73 m(2)), 118.8mol/l at 12 months (creatinine clearance: 55.8) and 132.4 mol/l at 24 months (creatinine clearance: 44.2). One year post-transplant, mean renal function measured by inulin clearance was 55.5 ml/min per 1.73 m(2). Four of the 15 patients had experienced an episode of acute rejection and three patients experienced delayed return of transplant function.Conclusion. - In view of the results obtained, the authors consider that dual kidney transplant could be a reasonable and effective option for selected patients. Positioning of the transplants in each itiac fossa limited the surgical complication rate. (c) 2008 Elsevier Masson SAS. Tous droits reserves.
Background. Intestinal microsporidiosis is a major cause of chronic diarrhea and malabsorption in patients with human immunodeficiency virus. Its occurrence in transplant recipients has exceptionally been reported to date.Methods. We report what we believe are the first two cases of intestinal microsporidiosis in renal transplant recipients. The patients were treated with mycophenolate mofetil.Results. The clinical presentation was chronic diarrhea with massive weight loss. Stool analysis revealed microsporidian spores, identified as Enterocytozoon bieneusi spores by polymerase chain reaction. The onset of this opportunistic infection in these two patients is believed to be secondary to an increase in immunosuppression after azathioprine replacement by mycophenolate mofetil. The withdrawal of mycophenolate mofetil led to clinical recovery.Conclusion. The incidence of microsporidiosis will probably increase in transplant recipients treated with powerful immunosuppressants. Therefore, we recommend a systematic search for microsporidian spores in stool specimens in cases of unexplained diarrhea in these patients.
We studied 104 patients - 45 females, 59 males - aged 20 to 64 years (mean = 42.4±11.5 years). All patients were recipients of cadaveric kidney transplants. They received conventional immunosuppressive therapy (prednisolone, ciclosporine, azathioprine).
In a retrospective study, we have analysed the outcome of the first and the second graft according to HLA compatibility and duration of the first graft.
: Following renal transplantation (RT), chronic immunosuppression is associated in hepatitis B virus (HBV) (+) patients with a flare-up of the disease, which might be harmful in the long term.: We report on the effect of long-term lamivudine therapy given at an initial daily dose of 100 mg in 18 HBV (+) RT patients.: When lamivudine therapy was commenced, 14 patients (77%) had an increase in their aspartate (AST) and alanine (ALT) aminotransferase levels. During a mean follow-up, under treatment, of 36.5 ± 3.5 months (up to 66 months), 10 patients (55%) had a sustained partial (HBV DNA < 4 × 105 copies/ml) (n = 4) or complete (HBV DNA < 400 copies/ml) (n = 6) virological response. Overall, 12 virological breakthroughs were observed. Of those who were HBe Ag(+) prior to lamivudine therapy (n = 4), one seroconverted to HBe Ab during therapy. At the last follow-up, AST and ALT levels were normal in 13 patients. When liver biopsy was repeated during treatment (n = 15), the virological responders showed a significant decrease in total Knodell score from 10 ± 0.6 to 7 ± 1 (P = 0.04), but no significant change in the stage of fibrosis. Conversely, in those patients with high HBV DNA titers, there were no significant changes in the total Knodell score or in the grade of fibrosis.: In conclusion, lamivudine therapy is safe in HBV(+)ve renal-transplant patients. However, even if the full and partial virological response rates are still high (55%) in the long term, relapse or primary non-responses occur. The implementation of alternative efficient strategies is warranted.
We observed 2 cases of disseminated tuberculosis with pulmonary miliary.
A 25 year old man was admitted to the transplant unit for an acute kidney graft pain which occured 20 hours before associated with oliguria. The chronic renal failure was due to reflux nephropathy. He underwent a kidney graft in November 1988. 2 kidney rejection episodes occured 10 days and 1 month after transplantation with a favorable out come. Baseline creatinemia stabilized around 150 micromol/L. Vascular graft thrill was noticed in January 1990. Systolodiastolic hypertension occured in February 1992, worsening progressively, with an impairement of the graft function. Angiography confirmed a slightly tight and stretched anastomotic and post anastomotic stenosis of the transplant artery. Transluminal angioplasty was performed with good inital results on hypertension and renal function. The thrill and hypertension reapered 10 months later. A new endoluminal dilatation was performed. Hypertension persisted but stenosis was non significant. Hypertension required Nifedipin 40 mg/day and Atenolol 50 mg/day. Creatininemia stabilized around 120 micromol/l. He was admitted in March 1995 for an acute graft pain and anuria. Angiography revealed complete thrombosis of the transplant artery. In situ fibrinolysis was performed with Recombinant Human Tissue-type Plasminogen Activator (Actilyse*). An in situ bolus of 10 mg was performed followed by an infusion of 40 mg for 45 mn. Total infusion was 1mg/kg. Continuous infusion of Heparin was started 12 hours after. An angiography performed 12 hours later confirmed the total desobstruction of the artery. Renal scintigraphy using Tc Mag 3 as tracer showed a good perfusion of the upper pole. He recovered diuresis after 3 days and satisfactory renal function after 3 weeks.
Data were collected over a period of 24 years (since the early 70s). During this period, 12 definite case-reports of treatment discontinuation were recorded.
Kaposi’s sarcoma (KS) or Kaposi’s disease has been especially observed in certain groups of patients: elderly individuals from Mediterranean countries or Central Europe, young Black Africans (“endemic forms”), AIDS patients (with a possibility of rapidly severe evolution of Kaposi’s disease), homosexual males without HIV infection, transplant patients treated with immunosuppressive therapy. The frequency of this disease, formerly relatively rare, and its evolutive course, comparatively slow in the past, have been significantly modified with the emergence of the AIDS epidemic and with the rapidly increasing number of patients subjected to prolonged immunosuppressive therapy to prevent transplant rejection.