RÉSUMÉ
BACKGROUND: Non-tuberculous mycobacteria (NTM) are present widely in the natural environment and can invade the human body through the respiratory tract, gastrointestinal tract, and skin. Immunocompromised patients are particularly prone to infection, which primarily affects multiple organs, including the lungs, lymph nodes, and skin. However, cases of NTM bloodstream infections are rare. Here, we report a rare case of Mycobacterium marseillense bloodstream infection with concurrent skin fungal infection in a patient after kidney transplantation. Related literature was reviewed to enhance the understanding of this rare condition. CASE PRESENTATION: A 58-year-old male with a history of long-term steroid and immunosuppressant use after kidney transplantation presented with limb swelling that worsened over the past two months. Physical examination revealed redness and swelling of the skin in all four limbs, with a non-healing wound on the lower left limb. Skin tissue analysis by metagenomic next-generation sequencing (mNGS) and fungal culture indicated infection with Trichophyton rubrum. Blood culture results suggested infection with Mycobacterium marseillense. After receiving anti-NTM treatment, the patient's symptoms significantly improved, and he is currently undergoing treatment. CONCLUSION: Mycobacterium marseillense is a NTM. Gram staining suffered from misdetection, and the acid-fast staining result was positive. This bacterium was identified by mass spectrometry and mNGS analyses. Antimicrobial susceptibility tests for NTM were performed using the broth microdilution method. The results of the susceptibility test showed that Mycobacterium marseillense was sensitive to clarithromycin, an intermediary between moxifloxacin and linezolid. Bacterial clearance requires a combination of drugs and an adequate course of treatment. NTM bloodstream infections are relatively rare, and early identification and proactive intervention are key to their successful management.
Sujet(s)
Infections à mycobactéries non tuberculeuses , Humains , Mâle , Adulte d'âge moyen , Infections à mycobactéries non tuberculeuses/microbiologie , Infections à mycobactéries non tuberculeuses/traitement médicamenteux , Mycoses cutanées/microbiologie , Mycoses cutanées/traitement médicamenteux , Transplantation rénale/effets indésirables , Sujet immunodéprimé , Antibactériens/usage thérapeutique , Mycobactéries non tuberculeuses/isolement et purification , Mycobactéries non tuberculeuses/effets des médicaments et des substances chimiques , Bactériémie/microbiologie , Bactériémie/traitement médicamenteux , Mycobacterium/isolement et purification , Mycobacterium/effets des médicaments et des substances chimiques , Peau/microbiologie , Peau/anatomopathologieRÉSUMÉ
As the global incidence of diabetes rises and diagnoses among younger patients increase, transplant centers worldwide are encountering more organ donors with diabetes. This study examined 80 donors and 160 recipients, including 30 donors with diabetes (DD) and their 60 recipients (DDR). The control group comprised 50 non-diabetic donors (ND) and 100 recipients (NDR). We analyzed clinical, biochemical, and pathological data for both diabetic and control groups, using logistic regression to identify risk factors for delayed graft function (DGF) after kidney transplantation. Results showed that pre-procurement blood urea nitrogen levels were significantly higher in DD [18.20 ± 10.63 vs. 10.86 ± 6.92, p = 0.002] compared to ND. Renal pathological damage in DD was notably more severe, likely contributing to the higher DGF incidence in DDR compared to NDR. Although DDR had poorer renal function during the first three months post-transplant, both groups showed similar renal function thereafter. No significant differences were observed in 1-year or 3-year mortality rates or graft failure rates between DDR and NDR. Notably, according to the Renal Pathology Society (RPS) grading system, kidneys from diabetic donors with a grade > IIb are associated with significantly lower postoperative survival rates. Recipient gender [OR: 5.452 (1.330-22.353), p = 0.013] and pre-transplant PRA positivity [OR: 34.879 (7.698-158.030), p < 0.001] were identified as independent predictors of DGF in DDR. In conclusion, transplant centers may consider utilizing kidneys from diabetic donors, provided they are evaluated pathologically, without adversely impacting recipient survival and graft failure rates.
Sujet(s)
Reprise retardée de fonction du greffon , Survie du greffon , Transplantation rénale , Complications postopératoires , Donneurs de tissus , Humains , Transplantation rénale/effets indésirables , Mâle , Femelle , Adulte d'âge moyen , Adulte , Reprise retardée de fonction du greffon/épidémiologie , Reprise retardée de fonction du greffon/étiologie , Facteurs de risque , Complications postopératoires/épidémiologie , Complications postopératoires/étiologie , Diabète/épidémiologie , Études rétrospectives , Rein/physiopathologie , Rein/anatomopathologie , Taux de survie , Modèles logistiques , IncidenceSujet(s)
Virus BK , Transplantation rénale , Infections à polyomavirus , Guides de bonnes pratiques cliniques comme sujet , Infections à virus oncogènes , Humains , Transplantation rénale/effets indésirables , Virus BK/pathogénicité , Infections à polyomavirus/virologie , Infections à polyomavirus/diagnostic , Infections à virus oncogènes/diagnostic , Infections à virus oncogènes/virologie , Consensus , Immunosuppresseurs/effets indésirables , Immunosuppresseurs/usage thérapeutique , Antiviraux/usage thérapeutiqueRÉSUMÉ
Renal transplantation is a life-saving treatment for patients with end-stage renal disease. However, the challenge of transplant rejection and the complications associated with immunosuppressants necessitates a deeper understanding of the underlying immune mechanisms. T cell exhaustion, a state characterized by impaired effector functions and sustained expression of inhibitory receptors, plays a dual role in renal transplantation. While moderate T cell exhaustion can aid in graft acceptance by regulating alloreactive T cell responses, excessive exhaustion may impair the recipient's ability to control viral infections and tumors, posing significant health risks. Moreover, drugs targeting T cell exhaustion to promote graft tolerance and using immune checkpoint inhibitors for cancer treatment in transplant recipients are areas deserving of further attention and research. This review aims to provide a comprehensive understanding of the changes in T cell exhaustion levels after renal transplantation and their implications for graft survival and patient outcomes. We discuss the molecular mechanisms underlying T cell exhaustion, the role of specific exhaustion markers, the potential impact of immunosuppressive therapies, and the pharmaceutical intervention on T cell exhaustion levels. Additionally, we demonstrate the potential to modulate T cell exhaustion favorably, enhancing graft survival. Future research should focus on the distinctions of T cell exhaustion across different immune states and subsets, as well as the interactions between exhausted T cells and other immune cells. Understanding these dynamics is crucial for optimizing transplant outcomes and ensuring long-term graft survival while maintaining immune competence.
Sujet(s)
Rejet du greffon , Transplantation rénale , Lymphocytes T , Transplantation rénale/effets indésirables , Humains , Lymphocytes T/immunologie , Rejet du greffon/immunologie , Rejet du greffon/prévention et contrôle , Survie du greffon/immunologie , Survie du greffon/effets des médicaments et des substances chimiques , Animaux , Immunosuppresseurs/usage thérapeutique , Immunosuppresseurs/effets indésirables , Défaillance rénale chronique/chirurgie , Défaillance rénale chronique/immunologie , Tolérance à la transplantation/immunologieRÉSUMÉ
BACKGROUND: Delayed graft function (DGF) after kidney transplantation is associated with adverse patients and allograft outcomes. A longer duration of DGF is predictive of worse graft outcomes compared to a shorter duration. Posttransplant serum ß2-microglobulin (B2M) is associated with long-term graft outcomes, but its relationship with DGF recovery is unknown. METHODS: We included all kidney-only transplant recipients with DGF enrolled in the E-DGF trial. Duration of DGF was defined as the interval between the transplant and the last dialysis session. We analyzed the association of standardized serum creatinine (Scr) and B2M on postoperative Days (POD) 1-7 during the subsequent days of DGF with the recovery of DGF. RESULTS: A total of 97 recipients with DGF were included. The mean duration of DGF was 11.0 ± 11.2 days. Higher Scr was not associated with the duration of DGF in unadjusted or adjusted models. Higher standardized B2M, in contrast, was associated with a prolonged duration of DGF. This association remained in models adjusting for baseline characteristics from POD 2 (3.19 days longer, 95% CI: 0.46-5.93; p = 0.02) through Day 6 of DGF (4.97 days longer, 95% CI: 0.75-9.20; p = 0.02). There was minimal change in mean Scr (0.01 ± 0. 10 mg/dL per day; p = 0.32), while B2M significantly decreased as the time to recovery approached (-0.14 ± 0.05 mg/L per day; p = 0.006), among recipients with DGF. CONCLUSION: B2M is more strongly associated with DGF recovery than Scr. Posttransplant B2M may be an important biomarker to monitor during DGF. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03864926.
Sujet(s)
Marqueurs biologiques , Reprise retardée de fonction du greffon , Débit de filtration glomérulaire , Survie du greffon , Transplantation rénale , bêta-2-Microglobuline , Humains , Transplantation rénale/effets indésirables , Reprise retardée de fonction du greffon/sang , Reprise retardée de fonction du greffon/étiologie , Femelle , Mâle , bêta-2-Microglobuline/sang , Adulte d'âge moyen , Pronostic , Marqueurs biologiques/sang , Études de suivi , Adulte , Facteurs de risque , Rejet du greffon/étiologie , Rejet du greffon/sang , Rejet du greffon/diagnostic , Défaillance rénale chronique/chirurgie , Défaillance rénale chronique/sang , Récupération fonctionnelle , Tests de la fonction rénale , Complications postopératoires/sang , Facteurs temps , Receveurs de transplantation/statistiques et données numériquesRÉSUMÉ
Previous studies of the immune control of cytomegalovirus infection have primarily focused on analysis of the traditional adaptive T-cell response. Donadeu et al. bring a new perspective through evaluation of multiple adaptive and innate immune subtypes in parallel with cytomegalovirus-specific cell-mediated immunity in a prospective cohort of kidney transplant recipients with findings validated in 2 independent studies. Identification of a natural killer T-cell subtype associated with cell-mediated immunity and freedom from cytomegalovirus infection demonstrates the importance of the coordinated innate and adaptive immune response for effective viral control.
Sujet(s)
Immunité acquise , Infections à cytomégalovirus , Cytomegalovirus , Immunité innée , Transplantation rénale , Infections à cytomégalovirus/immunologie , Infections à cytomégalovirus/prévention et contrôle , Humains , Transplantation rénale/effets indésirables , Cytomegalovirus/immunologie , Immunité cellulaire , Cellules T tueuses naturelles/immunologieRÉSUMÉ
RATIONALE: Renal artery rupture due to allograft infection, especially by fungi, is a serious clinical complication that can occur after kidney transplantation, and may lead to graft loss and death. PATIENT CONCERNS: Two kidney recipients from China who developed renal artery rupture at our hospital on 5 days (47-year-old female) and 45 days (39-year-old male) after surgery. DIAGNOSES: The male had immunoglobulin A nephropathy as a primary disease, and experienced a postoperative attack of vascular rejection and mixed infection by Mucor and bacteria. The female had chronic glomerulonephritis as a primary disease, and experienced renal artery rupture near the anastomosis site with infection by fungi and other pathogens. INTERVENTIONS: The male received resection of the implanted kidney and antibiotic therapy with intravenous vancomycin (0.5 g, 2 days) and amphotericin B (530 mg in 33 days). The female received replacing the segment of renal arterial and internal iliac artery by saphenous vein, as well as antibiotic therapy with amphotericin B (320 mg in 8 days). OUTCOMES: The male was recovered and received a second transplantation, while the female was discharged on postoperative day 19. LESSONS: In both patients, prompt surgery and aggressive treatment with an antifungal drug (amphotericin B) and antidrugs led to successful rescue.
Sujet(s)
Transplantation rénale , Artère rénale , Humains , Adulte d'âge moyen , Transplantation rénale/effets indésirables , Femelle , Mâle , Artère rénale/chirurgie , Adulte , Antifongiques/usage thérapeutique , Antibactériens/usage thérapeutique , Amphotéricine B/usage thérapeutique , Amphotéricine B/administration et posologie , Vancomycine/usage thérapeutique , Vancomycine/administration et posologie , Complications postopératoires/microbiologie , Complications postopératoires/étiologie , Rupture/chirurgieRÉSUMÉ
This study examines the interplay between human leukocyte antigen (HLA) compatibility and killer-cell immunoglobulin-like receptor (KIR) genotypes in influencing kidney transplantation outcomes. Understanding these interactions is crucial for improving graft survival and minimizing rejection risks. We evaluated 84 kidney transplant recipients, dividing them into two groups based on post-transplant outcomes: there were 68 with stable graft function (SGF) and 16 who experienced chronic rejection (CR). Patients were selected based on specific inclusion criteria. HLA mismatches (Class I: HLA-A, -B; Class II: HLA-DR) and KIR genotypes were determined using standard genotyping techniques. Statistical analyses, including logistic regression, were performed to correlate these factors with transplant outcomes. Significant age differences were observed, with younger patients more likely to experience graft rejection, while no significant gender-based differences were noted. A significant correlation was found between Class II mismatches and increased rejection rates, highlighting the importance of HLA-DR compatibility. Further analysis revealed that certain inhibitory KIRs, such as KIR3DL1, were associated with favorable outcomes, suggesting a protective role against graft rejection. These findings were corroborated by evaluating serum creatinine levels over multiple years, serving as a biomarker for renal function post transplant. This study underscores the critical need for meticulous HLA matching and the consideration of KIR genotypes in pre-transplant evaluations to enhance graft survival and minimize rejection risks. Integrating these genetic factors into routine clinical assessments could significantly improve personalized transplant medicine strategies, ultimately enhancing patient outcomes. Further research is needed to explore the underlying mechanisms and validate these findings in larger, diverse populations.
Sujet(s)
Génotype , Rejet du greffon , Survie du greffon , Transplantation rénale , Récepteurs KIR , Humains , Transplantation rénale/effets indésirables , Mâle , Femelle , Adulte d'âge moyen , Récepteurs KIR/génétique , Rejet du greffon/génétique , Rejet du greffon/immunologie , Adulte , Survie du greffon/génétique , Survie du greffon/immunologie , Antigènes HLA/génétique , Antigènes HLA/immunologie , Sujet âgéRÉSUMÉ
BACKGROUND: Epstein-Barr virus (EBV) is a herpesvirus linked to nine different human tumors and lymphoproliferative disorders. Immunosuppression promotes EBV-driven malignancies. The most frequent EBV-induced malignancies are lymphomas and nasopharyngeal carcinoma. By promoting smooth muscle proliferation, EBV can induce EBV-associated smooth muscle tumors (EBV-SMT). EBV-SMT is a rare oncological entity for which no current guideline for diagnosis or management exists. Data on posttransplant EBV-SMT (PT-SMT) are scarce in kidney transplant recipients. METHODS: We conducted a national multicentric retrospective study and collected cases among transplantation centers in France. Kidney transplant recipients experiencing histologically proven PT-SMT were included. We collected data on demographic characteristics of patient, history of kidney transplantation, history of PT-SMT, evolution of graft function, and patient survival. RESULTS: Eight patients were included. The median age at PT-SMT diagnosis was 31 years (range 6.5-40). PT-SMT occurred after a median delay of 37.8 months after transplantation (range 6-175). PT-SMT management consisted in immunosuppressive regimen minimization in all patients. Introduction of mTOR inhibitors was performed in two patients. Four patients (50%) needed chemotherapy. Surgical resection was performed in four patients. At last follow-up after PT-SMT diagnosis (median 33 months (range 17-132)), five patients were considered in complete remission, and two patients had died. Two patients experienced graft rejection; two resumed dialysis (25%). All patients with available data presented with impaired graft function at last follow-up. CONCLUSION: PT-SMT is a subacute and progressive disease during kidney transplantation. Even if the risk of developing PT-SMT is low in kidney transplant recipients (0.07% in our cohort), PT-SMT is associated with significant graft loss, possibly due to reduced immunosuppression. Developing guidelines could help transplantation teams better manage these patients.
Sujet(s)
Infections à virus Epstein-Barr , Herpèsvirus humain de type 4 , Transplantation rénale , Complications postopératoires , Tumeur du muscle lisse , Humains , Transplantation rénale/effets indésirables , Études rétrospectives , Mâle , Femelle , Tumeur du muscle lisse/virologie , Tumeur du muscle lisse/étiologie , Tumeur du muscle lisse/anatomopathologie , Tumeur du muscle lisse/diagnostic , Adulte , Études de suivi , Infections à virus Epstein-Barr/complications , Infections à virus Epstein-Barr/virologie , Herpèsvirus humain de type 4/isolement et purification , Pronostic , France/épidémiologie , Adolescent , Jeune adulte , Enfant , Complications postopératoires/diagnostic , Rejet du greffon/étiologie , Défaillance rénale chronique/chirurgie , Survie du greffon , Facteurs de risque , Tests de la fonction rénale , Débit de filtration glomérulaire , Taux de survieRÉSUMÉ
Background: C3 glomerulopathy (C3G), which encompasses C3GN and dense deposit disease (DDD), results from dysregulation of the alternative complement pathway. Data on disease recurrence after kidney transplantation are limited, and details on histologic features of recurrent C3G are scarce. We aimed to evaluate C3G recurrence in the allograft, with a focus on histologic presentation and progression. Methods: We retrospectively analyzed 18 patients with native kidney failure attributed to C3G (12 C3GN and six DDD), who received a kidney transplant from January 2016 to January 2023. Demographic, genetic, clinical, and histologic data were studied. The NanoString 770 genes PanCancer Immune Profiling Panel was used for transcriptomic analysis. Disease recurrence was the primary outcome. Results: During a median (interquartile range) follow-up period of 37 (1856) months, C3G recurrence occurred in 16 (89%) patients (11 with C3GN and five with DDD) at a median (interquartile range) of 33 (13141) days after transplantation. Over a third (38%) of recurrent cases were detected in protocol biopsies, and only 31% of patients presented with >300 mg/g of proteinuria. Recurrence in index biopsies was mainly established through a combination of immunofluorescence and electron microscopy findings, while it showed only subtle histologic alterations and no characteristic transcriptomic signals. Over time, histologic chronicity indices increased, but all the allografts were functioning at the end of follow-up. Patients with recurrence of C3GN and DDD showed overlapping immunofluorescence and electron microscopy findings and had similar recurrence rate and time to recurrence. Conclusions: Most of the patients with native kidney failure attributed to C3G developed disease recurrence very early after kidney transplantation, usually with minimal proteinuria, mild histologic alterations, and favorable short-term allograft survival. Immunofluorescence and electron microscopy played a crucial role in detecting early, subclinical recurrence of C3GN and DDD, which showed significant overlapping features.
Sujet(s)
Transplantation rénale , Récidive , Humains , Transplantation rénale/effets indésirables , Biopsie , Mâle , Complément C3/analyse , Facteurs temps , Adulte d'âge moyen , Femelle , Adulte , Glomérulonéphrite/anatomopathologieSujet(s)
Atteinte rénale aigüe , Transplantation rénale , Néphrolithiase , Donneurs de tissus , Humains , Transplantation rénale/effets indésirables , Atteinte rénale aigüe/étiologie , Néphrolithiase/étiologie , Mâle , Adulte d'âge moyen , Receveurs de transplantation , Pronostic , Femelle , Adulte , Complications postopératoires/étiologieRÉSUMÉ
INTRODUCTION: The study purpose was to review retrospectively our single-center experience transplanting kidneys from deceased donors (DD) with acute kidney injury (AKI) according to terminal serum creatinine (tSCr) level. METHODS: AKI kidneys were defined by a doubling of the DD's admission SCr and a tSCr ≥ 2.0 mg/dL. RESULTS: From 1/07 to 11/21, we transplanted 236 AKI DD kidneys, including 100 with a tSCr ≥ 3.0 mg/dL (high SCr AKI group, mean tSCr 4.2 mg/dL), and the remaining 136 from DDs with a tSCr of 2.0-2.99 mg/dL (lower SCr AKI group, mean tSCr 2.4 mg/dL). These two AKI groups were compared to 996 concurrent control patients receiving DD kidneys with a tSCr < 1.0 mg/dL. Mean follow-up was 69 months. Delayed graft function (DGF) rates were 51% versus 46% versus 29% (p < 0.0001), and 5-year patient and death-censored kidney graft survival rates were 96.8% versus 83.5% versus 82.2% (p = 0.002) and 86.7% versus 77.8% versus 78.8% (p = 0.18) in the high tSCr AKI versus lower tSCr AKI versus control groups, respectively. CONCLUSIONS: Despite a higher incidence of DGF, patients receiving kidneys from DDs with tSCr levels ≥3.0 mg/dL have acceptable medium-term outcomes compared to either AKI DDs with a lower tSCr or DDs with a tSCr < 1.0 mg/dL.
Sujet(s)
Atteinte rénale aigüe , Survie du greffon , Transplantation rénale , Donneurs de tissus , Humains , Atteinte rénale aigüe/étiologie , Transplantation rénale/effets indésirables , Mâle , Femelle , Études rétrospectives , Adulte d'âge moyen , Donneurs de tissus/ressources et distribution , Études de suivi , Pronostic , Taux de survie , Rejet du greffon/étiologie , Débit de filtration glomérulaire , Facteurs de risque , Reprise retardée de fonction du greffon/étiologie , Adulte , Tests de la fonction rénale , Complications postopératoires/étiologie , Créatinine/sang , Indice de gravité de la maladie , Défaillance rénale chronique/chirurgieRÉSUMÉ
BACKGROUND: There have been limited reports on immunosuppression strategies and outcomes in dual organ heart transplant populations, primarily from before the 2018 United Network for Organ Sharing (UNOS) heart allocation policy change. Recent data suggested that outcomes with heart-lung and heart-liver transplants remained comparable in the new allocation era, yet heart-kidney recipients have worse 1-year survival. METHODS: This single-center retrospective study evaluated adult heart-kidney, heart-liver, and heart-lung transplant recipients from September 2019 to May 2023. Immunosuppression regimen, infectious complications, and graft outcomes were collected for 12 months. RESULTS: A total of 36 patients (kidney n = 20, liver n = 9, and lung n = 7) were included in this study. Basiliximab was the most commonly employed induction strategy across the organ groups (12/20 in kidney, 4/9 in liver, and 7/7 in lung). All patients were on triple immunosuppression at 12 months posttransplant with prednisone wean achieved in one heart-liver recipient. Infection complications were frequently reported (95% kidney, 75% liver, 100% lung group). One patient went back to dialysis due to focal segmental glomerulosclerosis. One chronic lung allograft dysfunction was reported, but no other severe biopsy-proven rejection or retransplant was reported. The 1-year survival was 85% (17/20) in heart-kidney, 78% (7/9) in heart-liver, and 86% (6/7) in heart-lung recipients. CONCLUSION: This study summarized real-world immunosuppression strategies and outcomes in dual organ heart transplant recipients.
Sujet(s)
Rejet du greffon , Survie du greffon , Transplantation cardiaque , Immunosuppression thérapeutique , Immunosuppresseurs , Humains , Mâle , Femelle , Études rétrospectives , Transplantation cardiaque/effets indésirables , Transplantation cardiaque/mortalité , Adulte d'âge moyen , Études de suivi , Rejet du greffon/étiologie , Rejet du greffon/mortalité , Pronostic , Immunosuppression thérapeutique/méthodes , Immunosuppresseurs/usage thérapeutique , Adulte , Complications postopératoires , Taux de survie , Transplantation hépatique/mortalité , Transplantation hépatique/effets indésirables , Transplantation coeur-poumon/mortalité , Facteurs de risque , Transplantation rénale/effets indésirables , Transplantation rénale/mortalité , Prise en charge de la maladieRÉSUMÉ
Cytomegalovirus (CMV) infection is the main opportunistic infection observed after kidney transplantation. Despite the use of prevention strategies, CMV disease still occurs, especially in high-risk patients (donor seropositive/recipient seronegative). Patients may develop complicated CMV, i.e. recurrent, refractory or resistant CMV infection. CMV prevention relies on either universal prophylaxis or preemptive therapy. In high-risk patients, universal prophylaxis is usually preferred. Currently, valganciclovir is used in this setting. However, valganciclovir can be responsible for severe leucopenia and neutropenia. A novel anti-viral drug, letermovir, has been recently compared to valganciclovir. It was as efficient as valganciclovir to prevent CMV disease and induced less hematological side-effects. It is still not available in France in this indication. Recent studies suggest that immune monitoring by ELISPOT or Quantiferon can be useful to determine the duration of prophylaxis. Other studies suggest that prophylaxis may be skipped in CMV-seropositive kidney-transplant patients given mTOR inhibitors. Refractory CMV is defined by the lack of decrease of CMV DNAemia of at least 1 log10 at 2 weeks after effective treatment. In case of refractory CMV infection, drug resistant mutations should be looked for. Currently, maribavir is the gold standard therapy for refractory/resistant CMV. At 8 weeks therapy and 8 weeks later, it has been shown to be significantly more effective than other anti-viral drugs, i.e. high dose of ganciclovir, foscarnet or cidofovir. However, a high rate of relapse was observed after ceasing therapy. Hence, other therapeutic strategies should be evaluated in order to improve the sustained virological rate.
L'infection à cytomégalovirus (CMV) est la principale infection opportuniste après transplantation rénale. Malgré les stratégies préventives, il persiste des maladies à CMV, notamment chez les patients à haut risque (donneur séropositif/receveur séronégatif). Certains patients présentent des formes complexes avec des récurrences et des infections réfractaires et/ou résistantes aux antiviraux. La prévention de l'infection à CMV repose soit sur une prophylaxie universelle, soit sur une stratégie préemptive. Chez les patients à haut risque, la stratégie prophylactique est le plus souvent utilisée. Elle repose sur l'utilisation du valganciclovir, qui peut être responsable de leucopénies et de neutropénies sévères. Un nouvel antiviral, le létermovir, qui n'est pas encore disponible sur le marché en France dans cette indication, a montré une efficacité similaire au valganciclovir avec peu d'effets secondaires hématologiques. Des études récentes suggèrent l'intérêt de l'immuno-surveillance par ELISPOT ou Quantiféron pour guider la durée de la prophylaxie. D'autres études suggèrent également la possibilité de se passer d'un traitement prophylactique anti-CMV chez des transplantés rénaux CMV-séropositifs recevant des inhibiteurs de la mTOR. Le CMV réfractaire est défini par une absence de baisse de la charge virale d'au moins 1 log10 après deux semaines de traitement efficace. En cas d'absence de baisse de la charge virale, une recherche de mutations de résistance aux antiviraux doit être effectuée. Actuellement, le maribavir constitue le traitement de référence pour les formes réfractaires et résistantes. La clairance virale à la fin du traitement, ou huit semaines plus tard, est significativement supérieure à celle observée avec les autres antiviraux tels que le ganciclovir donné à forte dose, le foscarnet, ou le cidofovir. Cependant, le taux de rechute à l'arrêt du traitement par maribavir reste important. D'autres stratégies thérapeutiques doivent être évaluées pour améliorer ce taux de réponse virologique soutenue.
Sujet(s)
Antiviraux , Infections à cytomégalovirus , Transplantation rénale , Humains , Transplantation rénale/effets indésirables , Infections à cytomégalovirus/traitement médicamenteux , Infections à cytomégalovirus/prévention et contrôle , Antiviraux/usage thérapeutique , Valganciclovir/usage thérapeutique , Quinazolines/usage thérapeutique , Ganciclovir/usage thérapeutique , Ribonucléosides/usage thérapeutique , Acétates , Dichlororibofuranosylbenzimidazole/analogues et dérivésRÉSUMÉ
Posttransplant malignancies are an important complication of solid organ transplantation. Kidney transplant recipients are at particularly high risk of cancer development. The most relevant risk factors of carcinogenesis are the use of immunosuppressive agents and oncogenic viral infections. Additionally, immune dysregulation caused by these factors may predispose to various types of organ damage. Paraneoplastic glomerular diseases are one of the most interesting and understudied cancer manifestations. The appropriate diagnosis of paraneoplastic glomerular damage can be challenging in kidney transplant recipients, due to factors inherent to concomitant medication and common comorbidities. Recent advances in the field of molecular and clinical nephrology led to a significant improvement in our understanding of glomerular diseases and their more targeted treatment. On the other hand, introduction of novel anticancer drugs tremendously increased patients' survival, at the cost of kidney-related side effects. Our review aims to provide insights into diagnosis and treatment of paraneoplastic glomerular diseases, with a special attention to kidney transplant recipients.
Sujet(s)
Glomérulonéphrite , Transplantation rénale , Syndromes paranéoplasiques , Humains , Transplantation rénale/effets indésirables , Syndromes paranéoplasiques/étiologie , Facteurs de risque , Glomérulonéphrite/étiologie , Immunosuppresseurs/effets indésirables , Immunosuppresseurs/usage thérapeutique , Complications postopératoires/étiologie , Complications postopératoires/épidémiologie , Survie du greffonRÉSUMÉ
Delayed graft function (DGF) after kidney transplantation heralds a worse prognosis. In patients with hyperoxaluria, the incidence of DGF is high. Oxalic acid is a waste product that accumulates when kidney function decreases. We hypothesize that residual diuresis and accumulated waste products influence the DGF incidence. Patients transplanted between 2018-2022 participated in the prospective cohort study. Pre-transplant concentrations of oxalic acid and its precursors were determined. Data on residual diuresis and other recipient, donor or transplant related variables were collected. 496 patients were included, 154 were not on dialysis. Oxalic acid, and glyoxylic acid, were above upper normal concentrations in 98.8%, and 100% of patients. Residual diuresis was ≤150 mL/min in 24% of patients. DGF occurred in 157 patients. Multivariable binary logistic regression analysis demonstrated a significant influence of dialysis type, recipient BMI, donor type, age, and serum creatinine on the DGF risk. Residual diuresis and glycolic acid concentration were inversely proportionally related to this risk, glyoxylic acid directly proportionally. Results in the dialysis population showed the same results, but glyoxylic acid lacked significance. In conclusion, low residual diuresis is associated with increased DGF incidence. Possibly accumulated waste products also play a role. Pre-emptive transplantation may decrease the incidence of DGF.
Sujet(s)
Reprise retardée de fonction du greffon , Diurèse , Glyoxylates , Transplantation rénale , Acide oxalique , Humains , Transplantation rénale/effets indésirables , Femelle , Mâle , Adulte d'âge moyen , Reprise retardée de fonction du greffon/étiologie , Reprise retardée de fonction du greffon/épidémiologie , Adulte , Études prospectives , Sujet âgé , Dialyse rénale , Glycolates , Hyperoxalurie/étiologie , Facteurs de risque , IncidenceRÉSUMÉ
We aimed to investigate the clinical value of allograft biopsy performed long after renal transplantation. We retrospectively evaluated 99 allograft biopsies in recipients with transplantation vintages of 10 years or longer. Mixed-effects model showed that 1-year estimated glomerular filtration rate (eGFR) slopes after biopsy were significantly greater than those before biopsy [-3.13, -4.42 mL/min/1.73 m2/year, p = 0.01]. Renal biopsy changed the treatment strategies in more than half of the patients. Improvement in eGFR slopes was pronounced in 51 patients with treatment modification based on the biopsy results [2.27 (95% confidence interval (CI): 0.66, 3.89) mL/min/1.73 m2/year], whereas no improvement was observed in those without [0.33 (95% CI: -1.05, 1.71) mL/min/1.73 m2/year, Pinteraction = 0.001]. Among the treatment modifications, enhancement of immunosuppression (IS) led to the most remarkable improvement in eGFR slope. Patients with g scores ≥2 were more likely to receive IS enhancement than those with g scores = 0 [odds ratio; 15.0 (95% CI: 1.65, 136)]. Patients with active glomerulitis (g ≥ 1) without chronicity (cg ≤ 1) showed the most significant improvement in eGFR slope. Given the prevalence of active glomerulitis (g ≥ 1, 21%), which is responsive to treatment even long after transplantation, and the observed magnitude of eGFR slope improvement, renal biopsy can indeed improve allograft prognosis.
Sujet(s)
Allogreffes , Débit de filtration glomérulaire , Transplantation rénale , Rein , Humains , Transplantation rénale/effets indésirables , Mâle , Femelle , Biopsie , Études rétrospectives , Adulte d'âge moyen , Adulte , Rein/anatomopathologie , Facteurs temps , Immunosuppresseurs/usage thérapeutique , Rejet du greffon , Immunosuppression thérapeutique , Sujet âgéRÉSUMÉ
OBJECTIVE: It is unclear whether renal transplant recipients treated with mycophenolic acid (MPA) who carry the reduced-function allele at polymorphism SLCO1B1 c.521T>C differ from their wild-type peers regarding renal outcomes and tolerability. We aimed to estimate the effect of this polymorphism on the graft function (estimated glomerular filtration rate, eGFR) over the first 12 post-transplant months in patients on MPA-based maintenance immunosuppression. METHODS: In a 12-month observational cohort study, consecutive adult patients were repeatedly assessed for eGFR. The SLCO1B1 c.521C>T variant allele carriers (exposed) and wild-type subjects (controls) were balanced on a range of demographic, medical, and genetic variables at baseline, and eGFR trajectory was estimated with further adjustment for time-varying covariates. A subset of patients were assessed for exposure to MPA 5-7 days after the transplantation. RESULTS: The adjusted eGFR slopes from day 1 to day 28 (daily), and from day 28 to day 365 (monthly) were practically identical in exposed (nâ =â 86) and control (nâ =â 168) patients [geometric means ratios (GMR)â =â 0.99, 95% confidence interval (CI)â =â 0.92-1.06 and GMRâ =â 0.98, 0.94-1.01, respectively]. The rates of adverse renal outcomes and possible MPA-related adverse effects were low, and similar in exposed and controls [rate ratios (RR)â =â 0.94, 0.49-1.84 and RRâ =â 1.08, 0.74-1.58, respectively]. The pharmacokinetic analysis did not signal meaningful differences regarding exposure to MPA, overall (exposed nâ =â 23, control nâ =â 45), if cotreated with cyclosporine (nâ =â 17 vs. nâ =â 26) or with tacrolimus (nâ =â 8 vs. nâ =â 17). CONCLUSIONS: In patients treated with MPA, variant allele SLCO1B1 c.521T>C appears of no practical relevance regarding the 12-month renal graft function, MPA safety and exposure to MPA at early steady-state.
Sujet(s)
Débit de filtration glomérulaire , Transplantation rénale , Polypeptide C de transport d'anions organiques , Acide mycophénolique , Humains , Transplantation rénale/effets indésirables , Acide mycophénolique/effets indésirables , Acide mycophénolique/administration et posologie , Acide mycophénolique/pharmacocinétique , Mâle , Femelle , Adulte d'âge moyen , Débit de filtration glomérulaire/effets des médicaments et des substances chimiques , Adulte , Polypeptide C de transport d'anions organiques/génétique , Allèles , Immunosuppresseurs/effets indésirables , Immunosuppresseurs/administration et posologie , Immunosuppresseurs/pharmacocinétique , Immunosuppresseurs/usage thérapeutique , Polymorphisme de nucléotide simple , Sujet âgé , Études de cohortes , Rejet du greffon/génétique , Rejet du greffon/prévention et contrôleRÉSUMÉ
BACKGROUND: Immunosuppressive therapy is essential for to prevent graft rejection in renal transplant patients; however, it is associated with elevating the risk of several pathologies in these patients particularly infectious and neoplastic conditions. In this study, we explore the diagnosis and treatment of skin lesions in renal transplant patients. METHODS: A retrospective chart review of 12 renal transplant recipients referred to plastic and reconstructive surgery with skin lesions from 2000 to 2020 was performed. RESULTS: The mean age of the 12 patients was 49.6 years. Time to plastic surgery after renal transplantation ranged between 1 and 16 years. Nine cases of basal cell carcinoma, 2 cases of squamous cell carcinoma, and 1 case of skin and soft tissue infection of the lower extremity and cutaneous extranodal NK/T-cell lymphoma, nasal type was observed. Flaps, skin grafts, and artificial dermis grafts constitute the main reconstructive methods. There were no postoperative infections or wound dehiscence. CONCLUSIONS: Cutaneous infections and skin malignancy account for most of the skin lesions developing after renal transplantation. Posttransplant lymphoproliferative disorder warrants equal attention and should not be disregarded. Early diagnosis and treatment significantly improve prognosis as patients with longer duration of transplant were found to have more aggressive tumors. Plastic and reconstructive surgery offers a safe therapeutic method of treatment in these cases.