Le rejet humoral en transplantation rénale à Nancy (1er décembre 2003-31 mai 2005)

Le rejet humoral en transplantation d'organe, est un concept ancien, mais exploré de façon relativement récente. Il résulte de l'action d'anticorps spécifiques du donneur sur le greffon, et altère le pronostic à court terme mais aussi à long terme de l'organe transplanté. En greffe rénale, l'avènement du C4d, fraction du complément se liant de façon covalente à l'endothélium des c.apillaires péritubulaires, suite à l'interaction de ce dernier avec les alloanticorps, permit des progrès significatifs en matière de diagnostic du rejet, médié par les anticorps, aigu ou chronique. Il fut même considéré, au départ, par certains auteurs comme pathognomonique de l'implication de l'alloimmunité humorale en cas de dysfonction du greffon. Dans une étude rétrospective, nous avons tenté de déterminer l'incidence du rejet humoral au sein d'une population de patients transplantés entre le 1er décembre 2003 et le 31 mai 2005. Nous nous sommes tout particulièrement intéressés à l'évolution spontanée des patients ayant présenté des dépôts significatifs de C4d, sur une de leurs biopsies, mais aussi à ceux ayant développé une immunisation significative spécifique ou non dans les suites de leur transplantation. Dans les deux cas, ils devaient avoir présenté, un ou plusieurs épisodes de rejets. Une population de trente patients a ainsi pu être étudiée. Après analyse de leur évolution clinique, histologique et immunohistochimique, quatorze d'entre eux ont pu être identifiés, comme suspects d'avoir développé un rejet humoral, Cette étude, portant sur une série limitée de cas, nous apporte, cependant plusieurs enseignements. Tout d"abord, notre incidence d'épisodes de rejet humoral, serait plus faible que dans la littérature, 13,6% des épisodes de rejet contre 20 à 30%. Ceci résulte probablement d'un sous diagnostic, devant nous inciter à optimiser notre stratégie de détection des alloanticorps anti-HLA, du C4d et des signes histologiques. Enfin, le caractère pathognomonique du C4d semble en question au regard des évolutions de ces quatorze patients.NANCY1-Bib. numérique (543959902) / SudocSudocFranceF

Cohort study: “Outcomes of kidney transplantation in patients with prosthetic heart valves”

International audienceThe number of kidney transplant candidates with prosthetic heart valves (PHVs) is increasing. Yet, outcomes of kidney transplantation in these patients are still unclear. This is the first report of post-transplant outcomes in patients with PHVs at time of kidney transplantation. We conducted a matched cohort study among recipients from the multicentric and prospective DIVAT cohort to compare the outcomes in patients with left-sided PHVs at time of transplantation and a group of recipients without PHV matched according to age, dialysis time, initial disease, pretransplant DSA, diabetes, and cardiovascular events. Of 23 018 patients, 92 patients with PHVs were included and compared to 276 patients without PHV. Delayed graft function and postoperative bleeding occurred more frequently in patients with PHVs. Kidney graft survival was similar between groups. 5-year overall survival was 68.5% in patients with PHV vs. 87.9% in patients without PHV [HR, 2.72 (1.57-4.70), P = 0.0004]. Deaths from infection, endocarditis, and bleeding were more frequent in patients with PHV. Mechanical valves, but not bioprosthetic valves, were independent risk factors for mortality [HR, 2.89 (1.68-4.97), P = 0.0001]. Patients with PHV have high mortality rates after kidney transplantation. These data suggest that mechanical valves, but not biological valves, increase risks of post-transplant mortality

Kidney transplantation from expanded criteria donors: an increased risk of urinary complications. The UNyCORT* study

International audienceObjectives : To assess the impact of expanded criteria donors (ECD) on urinary complications in kidney transplantation.Patients and Methods : The UriNary Complications Of Renal Transplant (UNyCORT) is a cohort study based on the French prospective Données Informatisées et VAlidées en Transplantation/Computerized and VAlidated Data in Transplantation (DIVAT) cohort. Data were extracted between 1 January 2002 and 1 January 2018 with 1‐year minimum follow‐up, in relation to 44 pre‐ and postoperative variables. ECD status was included according to United Network for Organ Sharing (UNOS) definition. The primary outcome of the UNyCORT study was the association between the donor’s ECD/standard criteria donors (SCD) status and urinary complications at 1 year in uni‐ and multivariate analysis. Sub‐group analysis, stratified analysis on ECD/SCD donor’s status and transplant failure analysis were then conducted. Results : Between 1 January 2002 and 1 January 2018, 10 279 kidney transplants in adult recipients were recorded within the DIVAT network. A total of 8559 (83.4%) donors were deceased donors and 1699 (16.6%) were living donors (LD). Among donation after circulatory death (DCD) donors, 224 (2.85%) were uncontrolled DCD and 93 (1.09%) were controlled DCD donors. A total of 3617 (43.9%) deceased donors were ECD. The overall urological complication rate was 16.26%. The donor’s ECD status was significantly associated with an increased risk of urological complications at 1 year in multivariate analysis (odds ratio: 1.50, 95% CI 1.31–1.71; P < 0.001) and especially with stenosis and ureteric fistulae at 1 year. There is no association with LD, uncontrolled and controlled DCD. The placement of an endo‐ureteric stent was beneficial in preventing urinary complications in all donors and particularly in ECD donors. Conclusion : The donor’s ECD status is associated with a higher likelihood of stenosis and ureteric fistulae at 1 year. Recipients of grafts from ECD donors should probably be considered for closer urological monitoring and systematic preventive measures

Trajectories of glomerular filtration rate and progression to end stage kidney disease after kidney transplantation

Although the gold standard of monitoring kidney transplant function relies on glomerular filtration rate (GFR), little is known about GFR trajectories after transplantation, their determinants, and their association with outcomes. To evaluate these parameters we examined kidney transplant recipients receiving care at 15 academic centers. Patients underwent prospective monitoring of estimated GFR (eGFR) measurements, with assessment of clinical, functional, histological and immunological parameters. Additional validation took place in seven randomized controlled trials that included a total of 14,132 patients with 403,497 eGFR measurements. After a median follow-up of 6.5 years, 1,688 patients developed end-stage kidney disease. Using unsupervised latent class mixed models, we identified eight distinct eGFR trajectories. Multinomial regression models identified seven significant determinants of eGFR trajectories including donor age, eGFR, proteinuria, and several significant histological features: graft scarring, graft interstitial inflammation and tubulitis, microcirculation inflammation, and circulating anti-HLA donor specific antibodies. The eGFR trajectories were associated with progression to end stage kidney disease. These trajectories, their determinants and respective associations with end stage kidney disease were similar across cohorts, as well as in diverse clinical scenarios, therapeutic eras and in the seven randomized control trials. Thus, our results provide the basis for a trajectory-based assessment of kidney transplant patients for risk stratification and monitoring

The EKiTE network (epidemiology in kidney transplantation - a European validated database): an initiative epidemiological and translational European collaborative research

BACKGROUND: Kidney transplantation is considered to be the treatment of choice for people with end-stage renal disease (ESRD). However, due to the shortage of available organs and the increase in the ESRD prevalence in Europe, it is essential to improve transplantation outcomes by studying the related prognostic factors. Today, there is no European registry collecting data to perform such clinical epidemiology studies. MAIN BODY: Entitled EKiTE, for European cohort for Kidney Transplantation Epidemiology, this prospective and multicentric cohort includes patients from Spanish (Barcelona), Belgian (Leuven), Norwegian (Oslo) and French (Paris Necker, Lyon, Nantes, Nancy, Montpellier, Nice and Paris Saint Louis) transplantation centers and currently contains 13,394 adult recipients of kidney (only) transplantation from 2005 and updated annually. A large set of parameters collected from transplantation until graft failure or death with numbers of post-transplantation outcomes. The long-term follow-up and the collected data enable a wide range of possible survival and longitudinal analyses. CONCLUSION: EKiTE is a multicentric cohort aiming to better assess the natural history of the ESRD in European kidney transplant recipients and perform benchmarking of clinical practices. The data are available for clinical epidemiology studies and open for external investigators upon request to the scientific council. Short-term perspectives are to extend EKITE network to other European countries and collect additional parameters in respect of the common thesaurus.status: publishe