French Transplantation Centers Research Articles

Néphrectomie pour don de rein : quel système utiliser pour la ligature de l’artère rénale ? Aspects réglementaires et résultats de l’enquête nationale du CTAFU

Polymer Locking Clips (Weck* Hem-o-lok*, Teleflex Medical) are widely used for the vascular control during laparoscopic nephrectomy. However, those clips are contraindicated for use in ligating the renal artery during laparoscopic nephrectomies in living donor patients since 2005. We reviewed regulatory aspects, meta-analysis and guidelines published on the means used to ligate the renal artery during laparoscopic living donor nephrectomy. We although investigated among 31 French kidney transplant centers about their technic to occlude the renal artery. This survey was compared to those previously published in North America and in Europe.

Resolution of Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome (VOD/SOS) with Defibrotide Following HCT in Adult and Pediatric Patients: Pooled Analysis of Defifrance and EBMT PASS Registries

Introduction Veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a potentially life-threatening complication of hematopoietic cell transplantation (HCT). Defibrotide is approved for the treatment of severe VOD/SOS post-HCT in patients aged >1 month in the European Union and for VOD/SOS with renal or pulmonary dysfunction post-HCT in the United States. Outcomes from two real-world observational studies were pooled for analysis of treatment duration and time to resolution of VOD/SOS in patients given defibrotide for the treatment of severe or nonsevere VOD/SOS post-HCT. Methods DEFIFrance was an observational study that collected retrospective and prospective data on patients receiving defibrotide at 53 French transplant centers from July 2014 to March 2020. VOD/SOS severity was categorized retrospectively/prospectively using adult European Group for Blood and Marrow Transplantation (EBMT) criteria in patients aged ≥18 years, and in patients aged <18 years using pediatric EBMT criteria. EBMT PASS was a multinational, prospective, observational study that enrolled defibrotide-treated patients from April 2015 to July 2018. VOD/SOS severity was graded based on investigators' clinical expertise. For this pooled analysis, mild/moderate and severe/very severe cases in DEFIFrance were combined with nonsevere and severe cases in EBMT PASS, respectively. Investigators in both registries diagnosed VOD/SOS using classical/standard criteria. Results Overall, 414 defibrotide-treated patients with VOD/SOS post-HCT were included (336 from DEFIFrance and 78 from EBMT PASS). The median (interquartile range [IQR]) time from HCT to VOD/SOS diagnosis was 13 (IQR: 8, 21) and 14 (IQR: 8, 22) days in patients with severe and nonsevere VOD/SOS, respectively. Overall, 299/410 patients (73%) had resolution of VOD/SOS. Disease severity data was missing from 4 patients. Among 275 adult patients, VOD/SOS resolution was achieved in 44/60 (73.3%) with nonsevere and 128/215 (59.5%) with severe VOD/SOS. Median treatment duration was 15.5 days (IQR: 13, 22) for nonsevere and 18.5 days (IQR: 13.5, 22) for severe VOD/SOS. Of 135 pediatric patients, VOD/SOS resolution occurred in 47/48 (98%) with nonsevere and 80/87 (92%) with severe VOD/SOS. Median treatment duration was 16 days (IQR: 13, 21) in nonsevere and 21 days (IQR: 12.5, 29) in severe VOD/SOS. Among adult patients with resolution of VOD/SOS, symptoms resolved after day 21 in 32% of patients with nonsevere and 31% of patients with severe VOD/SOS. A higher proportion of pediatric patients with severe (44%) compared with nonsevere VOD/SOS (15%) required >21 days of treatment for resolution of symptoms; correspondingly, 85% of pediatric patients with nonsevere and 56% with severe VOD/SOS had resolution with ≤21 days of defibrotide treatment. Kaplan-Meier (KM)-estimated survival at day 100 post-HCT among patients with severe VOD/SOS was 84% (95% confidence interval [CI]: 78%, 88%) in those who achieved VOD/SOS resolution and 14% (95% CI: 8%, 22%) in those who did not; among patients with nonsevere VOD/SOS, this was 94% (95% CI: 87%, 98%) and 35% (95% CI: 15%, 57%), respectively. Serious treatment-emergent adverse events (TEAEs) of interest occurred in 25% of patients with VOD/SOS resolution. In patients treated for ≤21 days and >21 days, respectively, the most common serious TEAEs of interest by category were infection (14% and 15%) and hemorrhage (12% and 13%). Among patients with VOD/SOS resolution, the most common causes of death were infection (severe: 11%; nonsevere: 2%) and graft-versus-host disease (severe: 6%; nonsevere: 2%). Conclusion Time to resolution of VOD/SOS tended to be longer in patients with severe versus nonsevere VOD/SOS, with many patients requiring >21 days of therapy to achieve resolution. A higher proportion of adult vs pediatric patients attained a CR >21 days after initiation of defibrotide treatment. Day 100 survival was higher in patients with VOD/SOS resolution versus without, regardless of severity, highlighting the importance of VOD/SOS resolution. The safety profile of defibrotide in the real-world setting was consistent with reports from previous studies, supporting the utility of defibrotide treatment per the prescribing information.

Conversion From Intravenous In-Hospital Belatacept Injection to Subcutaneous Abatacept Injection in Kidney Transplant Recipients During the First COVID-19 Stay-at-Home Order in France.

The first COVID-19 stay-at-home order came into effect in France on 17 March 2020. Immunocompromised patients were asked to isolate themselves, and outpatient clinic visits were dramatically reduced. In order to avoid visits to the hospital by belatacept-treated kidney transplant recipients (KTRs) during the initial period of the pandemic, we promptly converted 176 KTRs at two French transplant centers from once-monthly 5mg/kg in-hospital belatacept infusion to once-weekly 125mg subcutaneous abatacept injection. At the end of follow-up (3months), 171 (97.16%) KTRs survived with a functioning graft, 2 (1.14%) had died, and 3 (1.70%) had experienced graft loss. Two patients (1.1%) experienced acute T cell-mediated rejection. Nineteen patients (10.80%) discontinued abatacept; 47% of the KTRs found the use of abatacept less restrictive than belatacept, and 38% would have preferred to continue abatacept. Mean eGFR remained stable compared to baseline. Seven patients (3.9%) had COVID-19; among these, two developed severe symptoms but survived. Only one patient had a de novo DSA. Side effects of abatacept injection were uncommon and non-severe. Our study reports for the first time in a large cohort that once-weekly injection of abatacept appears to be feasible and safe in KTRs previously treated with belatacept.

Monoclonal gammopathy of unknown significance in kidney transplanted patients: novel insights into long-term outcomes.

Because of increased access to kidney transplantation in elderly subjects, the prevalence of monoclonal gammopathies of unknown significance (MGUS) in kidney transplantation (KT) is growing. However, little is known about the consequences of MGUS on long-term outcomes. We identified 70 recipients with MGUS present at transplantation (KTMG) and 114 patients with MGUS occurring after KT (DNMG), among 3059 patients who underwent a KT in two French kidney transplantation centers. We compared outcomes of KTMG with those of matched controls. Baseline characteristics were similar except for an older age in KTMG compared with the DNMG group (62 vs 57 years, P=.03). Transient MGUS occurred more frequently in DNMG patients (45% vs 24%, P=.007). When compared with matched controls without MGUS, KTMG patients showed higher frequency and earlier post-transplant solid cancers (15% vs 5%, P=.04) and a trend for more bacterial infections (63% vs 48%, P=.08), without difference regarding patient and graft survival, rejection episodes or hematological complications. KTMG patients with an abnormal kappa/lambda ratio and/or severe hypogammaglobulinemia at the time of KT experienced shorter overall survival. MGUS detection at the time of KT is neither associated with a higher occurrence of graft rejection, nor adversely affects graft or overall survival. MGUS should not contraindicate KT. However, MGUS at the time of KT may be associated with higher risk of early neoplastic and infectious complications and warrants prolonged surveillance. Measurement of serum free light chain should be performed before transplant to refine the risk evaluation of KTMG patients and propose personalized follow-up and immunosuppression.

Impact of newly diagnosed prostate cancer at time of evaluation for renal transplantation.

Systematic screening for prostate cancer is widely recommended in candidates for renal transplant at the time of listing. There are concerns that overdiagnosis of low-risk prostate cancer may result in reducing access to transplant without demonstrated oncological benefits. The objective of the study was to assess the outcome of newly diagnosed prostate cancer in candidates for transplant at the time of listing, and its impact on transplant access and transplant outcomes according to treatment options. This retrospective study was conducted over 10 years in 12 French transplant centers. Patients included were candidates for renal transplant at the time of prostate cancer diagnosis. Demographical and clinical data regarding renal disease, prostate cancer, and transplant surgery were collected. The primary outcome of the study was the interval between prostate cancer diagnosis and active listing according to treatment options. Overall median time from prostate cancer diagnosis to active listing was 25.0 months [16.4-40.2], with statistically significant differences in median time between the radiotherapy and the active surveillance groups (p=.03). Prostate cancer treatment modalities had limited impact on access and outcome of renal transplantation. Active surveillance in low-risk patients does not seem to compromise access to renal transplantation, nor does it impact oncological outcomes.

Information and Communication Technologies in Lung Transplantation: Perception of Patients and Medical Teams

Optimal therapeutic management is a major determinant of patient prognosis and healthcare costs. Information and communication technologies (ICTs) represent an opportunity to enhance therapeutic management in complex chronic diseases, such as lung transplantation (LT). The objective of this study was to assess the preferences of LT patients and healthcare professionals regarding ICTs in LT therapeutic management. A cross-sectional opinion survey was conducted among lung transplant patients and healthcare professionals from the French lung transplantation centers. Five ICTs were defined (SMS, email, phone, internet, and smartphone application) in addition to face-to-face communication. An unsupervised approach by Principal Component Analysis (PCA) identified lung transplant patient profiles according to their preferences for ICTs. Fifty-three lung transplant patients and 15 healthcare professionals of the French LT centers were included. Both expected ICTs for treatment management and communication. Phone call, face-to-face, and emails were the most preferred communication tools for treatment changes and initiation. PCA identified four ICTs-related profiles (“no ICT”, “email”, “SMS”, and “oral communication”). “Email” and “oral communication” profiles are mainly concerned with treatment changes and transmission of new prescriptions. The “SMS” profile expected reminders for healthcare appointments and optimizing therapeutic management. This study provides practical guidance to enhance LT therapeutic management by ICT intervention. The type of ICT used should take into account patient profiles to improve adherence and thereby the prognosis. A combination of strategies including information, education by a multidisciplinary team, and reminders is a promising approach to ensure an optimal management of our patients.

Early Post-Transplant Red Blood Cell Transfusion Is Associated With an Increased Risk of Transplant Failure: A Nationwide French Study.

BackgroundRed blood cell (RBC) transfusions are frequently required in the early period after kidney transplantation. However, the consequences of RBC transfusions on long-term outcomes are largely unrecognized.MethodsWe conducted a nationwide French cohort study involving all 31 French kidney transplant centers. Patients having received a first kidney transplant between January 1, 2002 and December 31, 2008 were identified through the national registry of the French BioMedecine Agency (Agence de BioMédecine). Number and date of RBC transfusions were collected from the national database of the French transfusion public service. The primary endpoint was transplant failure defined as graft loss or death with a functional graft.ResultsAmong 12,559 patients included during the study period, 3,483 (28%) were transfused during the first 14 days post-transplant. Median follow-up was 7.6 (7.5-7.8) years. Multivariable analysis determined that post-transplant RBC transfusion was associated with an increased risk in transplant failure (HR 1.650, 95%CI [1.538;1.771] p<0.0001). Both sensitivity and propension score analyses confirmed the previous result.ConclusionsEarly red blood cell transfusion after kidney transplantation is associated with increased transplant failure.

IgG3 donor–specific antibodies with a proinflammatory glycosylation profile may be associated with the risk of antibody-mediated rejection after kidney transplantation

The pathogenicity of de novo donor-specific antibodies (dnDSA) varies according to their characteristics. While their MFI, complement-fixing ability, and IgG3subclass are associated with ABMR occurrence and graft loss, they are not fully predictive of outcomes. We investigated the role of the Fc glycosylation of IgG3 dnDSA in ABMR occurrence using mass spectrometry after isolation by single HLA antigen beads. Between 2014 and 2018, we enrolled 54 patients who developed dnDSA (ABMR- n=24; ABMR+ n=30) in two French transplant centers. Fucosylation, galactosylation, GlcNAc bisection, and sialylation of IgG3 dnDSA were compared between ABMR+ and ABMR- patients. IgG3 dnDSA from ABMR+ patients exhibited significantly lower sialylation (7.5% vs. 10.5%, p<.001) and higher GlcNAc bisection (20.6% vs. 17.4%, p=.008). Fucosylation and galactosylation were similar in both groups. DSA glycosylation was not correlated with DSA MFI. In a multivariate analysis, low IgG3sialylation, high IgG3%, time from transplantation to kidney biopsy, and tacrolimus-free regimen were independent predictive factors of ABMR. We conclude that a proinflammatory glycosylation profile of IgG3 dnDSA is associated with a risk of ABMR occurrence. Further studies are needed to confirm the clinical interest of DSA glycosylation and to clarify its role in determining the risk of ABMR and graft survival.

COVID-19 et transplantation d’organes, les leçons du recensement national de la Société francophone de transplantation

La pandémie de Covid-19 a frappé le monde de la transplantation en mars 2020. Rapidement, les équipes se sont organisées pour optimiser la prise en charge de leurs patients immunodéprimés et progresser dans la connaissance de cette nouvelle maladie. Pour ce faire, un registre français regroupant tous les patients transplantés d’organes solides ayant développé une infection à SARS Cov2 ont été recensés. De nombreux travaux réalisés à partir de ces données nous ont permis de décrire la maladie chez le transplanté, de caractériser ses facteurs de gravité clinique et biologique et d’en définir son pronostic. La mortalité des patients transplantés hospitalisés pour Covid-19 est de 23 % à 60 jours et l’insuffisance rénale participe grandement au mauvais pronostic en sus des facteurs de risque classiques décrits dans la population générale. L’arrivée de la vaccination a été un grand soulagement mais les patients transplantés ont développé une moins bonne réponse vaccinale que les sujets immunocompétents les maintenant dans une situation à risque de maladie grave après un schéma vaccinal adapté. Des stratégies spécifiques ont dû être adoptées dans cette population particulièrement fragile (augmentation du nombre de doses de vaccin, injection d’anticorps monoclonaux). La collaboration des centres de transplantation français sous l’impulsion de la Société francophone de transplantation nous a permis de mener de nombreux projets collaboratifs qui ont été d’une grande utilité pour la prise en charge des patients.

Liver transplantation for critically ill cirrhotic patients: Results from the French transplant registry

This study describes the population of cirrhotic patients who were transplanted from the ICU in France, identifying pre-transplant risk factors of post-transplant mortality and describing geographic variations in ICU transplant activity.Cirrhotic patients transplanted between 2008 and 2018 were included through the national transplant registry. The demographic, clinical and biological characteristics of the patients transplanted from the ICU were compared to cirrhotic patients who were transplanted from home or from the hospital. Risk factors of post-transplant one-year mortality were identified in uni- and multivariable analysis within the population transplanted from the ICU. Funnel plots were used to illustrate center-specific differences in ICU transplant activity.1,047 cirrhotic patients were transplanted from the ICU during the study period. While the national rate of transplants performed from the ICU was 14.3% the absolute number and the rate of cirrhotic patients transplanted from the ICU varied significantly from one center to another, ranging from 6.6% to 22.8% (p < 0.05). Three recipient-associated independent risk factors one-year post-LT mortality were identified in the population transplanted from the ICU: age > 50 years (HR 1.65, 95%CI 1.16–2.36), p = 0.005), diabetes (HR 1.46, 95%CI 1.07–1.98, p = 0.02) and intubation (HR2.12, 95%CI 1.62-2.78), p < 0.001). Donor age was also independently associated with mortality (HR 1.01, 95%CI 1.01–1.02, p < 0.001). Funnel plots showed significant differences in the proportion of patients transplanted from the ICU and the distribution of risk factors across French transplant centers, especially the inclination to transplant intubated patients.This study underlines the increased post-transplant mortality among cirrhotic patients transplanted from the ICU. It identifies four clinically pertinent independent risk factors associated with post-transplant mortality in this specific sub-group of transplant candidates. Finally, it illustrates how diverse the landscape of liver transplantation for critically ill cirrhotic patients is across a single country, despite a unified allocation algorithm.

Pulmonary Alveolar Proteinosis After Allogeneic Hematopoietic Stem-Cell Transplantation in Adults: A French Société Francophone de Greffe de Moelle et Thérapie Cellulaire Survey

Pulmonary alveolar proteinosis (PAP) is related to a dysfunction in surfactant clearance by alveolar macrophages.1 It can be autoimmune (aPAP) due to anti-granulocyte-colony stimulating factor (GM-CSF) autoantibodies, hereditary, in relation with mutations in genes coding for subunits of the GM-CSF receptor or surfactant proteins, or secondary (sPAP) to hematologic diseases or environmental or drug exposure that alters alveolar macrophage functions.2 We conducted a national survey with the help of French Society of Bone-Marrow Transplantation and Cellular Therapy that questioned the 43 French hematopoietic stem cell transplantation (HSCT) centers about adult-onset PAP after allogeneic hematopoietic stem-cell allograft.

FC 126IMPACT OF POLYCLONAL ANTI-T-LYMPHOCYTE IMMUNOGLOBULINS ON THE RECURRENCE OF IGA NEPHROPATHY AFTER KIDNEY TRANSPLANTATION: THE PIRAT STUDY

Abstract Background and Aims IgA Nephropathy (IgAN) often recurs on kidney transplants, accounting for a significant specific kidney failure occurrence after ten years of transplantation vintage. Polyclonal anti-T-lymphocyte antibodies (PATLA) immunosuppressive induction has been shown to be associated with a lower rate of IgAN recurrence compared to basiliximab and no induction in a retrospective study. The aim of the PIRAT study was to compare an induction by PATLA versus basiliximab by the mean of a randomized controlled trial. Method Adults with biopsy-proven primary IgAN as primary cause of end stage of renal disease, first transplantation, panel reactive antibody &amp;lt;50% could be included in the study. Patients were randomized 1:1 prior to transplantation to receive either PATLA (Grafalon, 4mg/kg for 3 days, then two days 3mg/kg) or basiliximab (20mg at transplantation and 4 days after). Both groups received methylprednisolone followed by oral corticoids for at least one year, tacrolimus and mycophenolic acid. Primary outcome was the clinico-histological recurrence defined by both IgA deposition on transplant biopsy and albuminuria&amp;gt;300mg/d during 5 years post-transplantation. Protocol biopsy at 5 years was highly recommended. Results A total of 117 patients were finally included in 13 French transplant centers, with 60 patients in the PATLA group and 57 in the basiliximab control group. Both groups were similar (median, PATLA vs. basiliximab, p&amp;gt;0.05 wilcoxon test) in term of sex ratio (4.45 vs 4.57), recipient age (47.9 vs. 47.7 years old), dialysis vintage (26.2 vs. 24.6 months), age at IgAN diagnosis (35.0 vs. 42.2 years old), cold ischemia (780 min vs 682 min), warm ischemia (34 vs. 36.1min), proportion of living donors (33% vs. 25%). The 5-year protocol biopsy was performed on 48% vs. 45% of patients, with overall proportion of patients evaluated by at least one biopsy of 63% vs. 66%. A trend in favor to the protection by PATLA from the occurrence of a clinico-histological recurrence was found (hazard ratio, univariate Cox model 0,35 [0.11-1.1], p=0.082). Biopsy proven histological recurrence was significantly lower after PATLA induction (HR 0.34 [0.16-0.76], p=0.0079). PATLA group experienced more infections (40 vs. 28 p=0.06), a lower number of graft losses (3 vs 9, p=0.07), a lower number of biopsy-proven acute rejections (5 vs 10, p=0.17). Similar rates of cytomegalovirus and BK virus infections were found. Conclusion PATLA for immunosuppressive induction was found protective from the recurrence of IgA deposition during the first 5 years after transplantation, compared to basiliximab. A similar trend, although not significant, was found about the clinico-histological recurrence which was the predefined primary outcome.

COVID-19 severity in kidney transplant recipients is similar to nontransplant patients with similar comorbidities.

Higher rates of severe COVID‐19 have been reported in kidney transplant recipients (KTRs) compared to nontransplant patients. We aimed to determine if poorer outcomes were specifically related to chronic immunosuppression or underlying comorbidities. We used a 1:1 propensity score‐matching method to compare survival and severe disease‐free survival (defined as death and/or need for intensive care unit [ICU]) incidence in hospitalized KTRs and nontransplant control patients between February 26 and May 22, 2020. Patients were matched for risk factors of severe COVID‐19: age, sex, body mass index, diabetes mellitus, preexisting cardiopathy, chronic lung disease, and basal renal function. We included 100 KTRs (median age [interquartile range (IQR)]) 64.7 years (55.3–73.1) in three French transplant centers. After a median follow‐up of 13 days (7–30), transfer to ICU was required for 34 patients (34%) and death occurred in 26 patients (26%). Overall, 43 patients (43%) developed a severe disease during a median follow‐up of 8.5 days (2–14). Propensity score matching to a large French cohort of 2017 patients hospitalized in 24 centers, revealed that survival was similar between KTRs and matched nontransplant patients with respective 30‐day survival of 62.9% and 71% (p = .38) and severe disease‐free 30‐day survival of 50.6% and 47.5% (p = .91). These findings suggest that severity of COVID‐19 in KTRs is related to their associated comorbidities and not to chronic immunosuppression.

Management of Immunosuppression After Kidney Transplant Failure: Effect on Patient Sensitization

BackgroundImmunosuppressive treatment is often interrupted in the first months following kidney transplant failure (KTF) to limit side effects. The aim of this study was to assess the effect of prolonged treatment (PT) of more than 3 months’ duration after KTF on HLA sensitization and treatment tolerance. MethodsWe performed a retrospective observational study involving 119 patients with KTF in 3 French kidney transplant centers between June 2007 and June 2017. Sensitization was defined as the development of HLA donor-specific antibodies (DSA). ResultsIn the PT group receiving calcineurin inhibitor (CNI) treatment, 30 of 52 patients (57.7%) were sensitized vs 52 of 67 patients (77.6%) who had early cessation of treatment (P = .02). The results were confirmed by multivariate analysis (odds ratio [OR] = 0.39, 95% confidence interval [CI] [0.16; 0.98], P = .04). The development of de novo DSAs after CNI treatment (n = 63/90 [70.0%]) was significantly more frequent than during CNI treatment, (n = 18/52 [34.6%], P = .01). Panel-reactive antibody ≥85% was lower in the PT group in multivariate analysis (OR = 0.28, 95% CI [0.10; 0.78], P = .02). No differences in the rates of infection, cardiovascular complications, neoplasia, and deaths were observed between the 2 groups. In multivariate analysis, continuation of corticosteroid treatment had no influence on sensitization but was associated with a higher rate of infection (OR = 2.66, 95% CI [1.09; 6.46], P = .03). ConclusionMaintenance of CNI treatment after return to dialysis in patients requesting a repeat transplant could avoid the development of anti-HLA sensitization with a good tolerance.

Conversion From Belatacept to Another Immunosuppressive Regimen in Maintenance Kidney-Transplantation Patients

IntroductionDuring the coronavirus disease 2019 (Covid-19) pandemic, several physicians have questioned pursuing belatacept in kidney-transplant patients in order to reduce the risk of nosocomial transmission during the monthly infusion. The effect of the conversion from belatacept to another immunosuppressive regimen is underreported. The aim of the present retrospective study was to assess the effect on kidney function and the clinical outcome of the conversion from belatacept to another regimen.MethodsWe have identified 44 maintenance kidney transplantation patients from five French kidney transplantation centers who were converted from belatacept to another regimen either because of a complication (n = 28) or another reason (patients’ request or belatacept shortage, n = 13). The follow-up after the conversion from belatacept was 27.5 ± 25.3 months.ResultsOverall, mean estimated glomerular filtration rate (eGFR) decreased from 44.2 ± 16 ml/min per 1.73 m2 at conversion from belatacept to 35.7 ± 18.4 ml/min per 1.73 m2 at last follow-up (P = 0.0002). eGFR significantly decreased in patients who had been given belatacept at transplantation as well as in those who had been converted to belatacept earlier. The decrease was less significant in patients who had stopped belatacept without having experienced any complications. Finally, eGFR decreased more severely in patients who were converted to calcineurin inhibitors (CNIs), compared to those who received mammalian target of rapamycin inhibitor (mTORi). Few patients also developed diabetes and hypertension.ConclusionsThus, transplantation physicians should avoid stopping belatacept when not clinically required.

Provision of information on transplantation to cystic fibrosis patients and their relatives: Overview of French practices and recommendations

BackgroundHow health-care professionals inform cystic fibrosis patients and their relatives about transplantation is not well known. Such information may not be provided in a timely or satisfactory manner. We conducted a survey about patient information practices among professionals from all French cystic fibrosis centers and transplant centers, to determine how they might be improved. MethodsThis was a national, retrospective, multicenter, descriptive assessment of practices involving health-care professionals, transplant recipients and their relatives, and peer patients who are themselves transplant recipients. Questionnaires were developed by the French working group on cystic fibrosis patient education (GETHEM: Groupe éducation thérapeutique et mucoviscidose). At the end of the questionnaires, respondents were invited to suggest ways to improve the current process. ResultsIn all, 216 professionals, 55 patients, 30 relatives of these patients, and 17 peer patients responded to the questionnaires, which addressed topics in chronological order, from neonatal screening or later diagnosis of the illness to the time of the transplant, if one was performed. ConclusionsStudy findings have allowed us to draft nine recommendations for professionals to improve patient information practices. A booklet now being prepared aims to facilitate the process for professionals, and e-learning modules are also forthcoming.

Antibiotic therapy in case of positive cultures of kidney transplant preservation fluid: a nationwide survey of prescribing practices.

Our survey aimed to describe current prescribing practices for perioperative antibiotic prophylaxis in French kidney transplant centers. We conducted a nationwide cross-sectional clinical vignette-based survey that we sent via email to hospital practitioners involved in perioperative management of kidney transplant patients (KTR). Nearly half of practitioners contacted (182/427, 42.6%) were respondents. A total of 167 getting enough kidney transplant activity were eligible for the survey. The response rate was 50.7% (68/134) among interns and 33.8% (99/293) among seniors. Positive perfusion fluids (PF) cultures for methicillin-susceptible Staphylococcus aureus were associated with antibiotic prescribing in 35% of cases, with no difference in prescribing in patients with diabetes, obesity, or delayed graft function. Antibiotic prescribing was most frequent with Pseudomonas aeruginosa (67%) and Klebsiella pneumoniae strains producing extended spectrum β-lactamases (57%). About 77%, 16%, and 13% of respondents, respectively, reported the existence of local practice guidelines for surgical antibiotic prophylaxis, a standardized approach for antibiotic prescribing in case of positive kidney transplant PF cultures, and local practice guidelines for systematical antibiotic prophylaxis in the early post-transplant period. In France, antibiotic prophylaxis practices in the perioperative kidney transplant period are very heterogeneous. To prevent unnecessary prescribing and bacterial resistance, evidence-based practice guidelines should be developed.

Long-term Outcome of Renal Transplantation in Patients with Congenital Lower Urinary Tract Malformations: A Multicenter Study.

Renal insufficiency can occur in patients with congenital lower urinary tract malformations (LUTM) even when managed during infancy. Data in the current literature concerning this subject remain sparse. The aim of this study was to report the feasibility and long-term results of renal transplantation during adulthood in patients with a congenital LUTM. A retrospective multicenter study from 3 French renal transplant centers was conducted, including 123 transplantations on 112 patients with LUTM (1996-2016). Graft survival, patient survival, and complications were analyzed. Results were stratified according to the underlying uropathy and the type of initial management during childhood or before transplantation. In this study, patients suffering from posterior urethral valves (n = 49), spina bifida (n = 21), central neurogenic bladder (n = 13), bladder exstrophy (n = 14), prune belly syndrome (n = 12), Hinman syndrome (n = 6), urogenital sinus (n = 4), and other pathologies (n = 4) were included. The mean age at transplantation was 32.1 years old (±11.2). The mean follow-up period was 7.2 years. Patient survival at 1, 5, 10, and 15 years was 97.4%, 93.0%, 89.4%, and 80.0%, respectively. Graft survival at 1, 5, 10, 15, and 20 years was 96.6%, 87.6%, 77.3%, 60.6%, and 36.4%, respectively. Enterocystoplasty and continent urinary diversions exposed grafts to more frequent acute pyelonephritis (P = 0.02). There was no difference in graft survival when transplantation was performed on an enterocystoplasty or urinary diversions compared with a native bladder, provided a well-conducted bladder management. Even though enterocystoplasty and continent urinary diversions exposed grafts to more frequent acute graft pyelonephritis, patient and graft survival rates in LUTM at 10 years were similar to other kidney transplantations on native bladders.

Outcome of Liver Transplant Patients With Preformed Donor-Specific Anti-Human Leukocyte Antigen Antibodies.

After liver transplantation (LT), the role of preformed donor-specific anti-human leukocyteantigen antibodies (pDSAs) remains incompletely understood. We conducted a retrospective, case-control analysis to determine the impact of pDSAs after LT in 3 French transplant centers (Bordeaux, Lyon, and Toulouse). Among the 1788 LTs performed during the study period, 142 (7.9%) had at least 1 pDSA. The patient survival rate was not different between patients who received an LT with pDSAs and the matched-control group. A liver biopsy was performed 1year after transplantation in 87 recipients. The metavir fibrosis score did not differ between both groups (1±0.8 versus 0±0.8; P=0.80). However, undergoing a retransplantation (hazard ratio [HR]=2.6, 95% confidence interval [CI], 1.02-6.77; P=0.05) and receiving induction therapy with polyclonal antibodies (HR=2.5; 95% CI, 1.33-4.74; P=0.01) were associated with a higher risk of mortality. Nonetheless, high mean fluorescence intensity (MFI) donor-specific antibodies (ie, >10,000 with One Lambda assay or >5000 with Immucor assay) were associated with an increased risk of acute rejection (HR=2.0; 95% CI, 1.12-3.49; P=0.02). Acute antibody-mediated rejection was diagnosed in 10 patients: 8 recipients were alive 34 (1-125) months after rejection. The use of polyclonal antibodies or rituximab as an induction therapy did not reduce the risk of acute rejection, but it increased the risk of infectious complications. In conclusion, high MFI pDSAs increase the risk of graft rejection after LT, but they do not reduce medium-term and longterm patient survival. The use of a T or B cell-depleting agent did not reduce the risk of acute rejection.

Natural History of Recurrent Alcohol-Related Cirrhosis After Liver Transplantation: Fast and Furious.

Alcohol-related liver disease (ALD) is one of the main indications for liver transplantation (LT). Severe alcohol relapse can rapidly lead to recurrent alcohol-related cirrhosis (RAC) for the graft. The aim of this study was to describe the natural history of RAC and the overall survival after LT and after an RAC diagnosis. From 1992 to 2012, 812 patients underwent primary LT for ALD in 5 French transplant centers. All patients with severe alcohol relapse and an RAC diagnosis on the graft were included. The diagnosis of cirrhosis was based on the analysis of liver biopsy or on the association of clinical, biological, radiological, and/or endoscopic features of cirrhosis. RAC was diagnosed in 57/162 patients (35.2%) with severe alcohol relapse, and 31 (54.4%) of those patients had at least 1 episode of liver decompensation. The main types of decompensation were ascites (70.9%), jaundice (58.0%), and hepatic encephalopathy (9.6%). The cumulative probability of decompensation was 23.8% at 5years, 50.1% at 10years, and 69.9% at 15years after LT. During the follow-up, 36 (63.2%) patients died, the main cause of death being liver failure (61.1%). After diagnosis of cirrhosis, the survival rate was 66.3% at 1year, 37.8% at 5years, and 20.6% at 10years. In conclusion, RAC is associated with a high risk of liver decompensation and a poor prognosis. Prevention of severe alcohol relapse after LT is a major goal to improve patient survival.