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1.
Transpl Int ; 37: 12475, 2024.
Article in English | MEDLINE | ID: mdl-38665475

ABSTRACT

An increasing number of sensitized patients awaiting transplantation face limited options, leading to fatalities during dialysis and higher costs. The absence of established evidence highlights the need for collaborative consensus. Donor-specific antibodies (DSA)-triggered antibody-mediated rejection (AMR) significantly contributes to kidney graft failure, especially in sensitized patients. The European Society for Organ Transplantation (ESOT) launched the ENGAGE initiative, categorizing sensitized candidates by AMR risk to improve patient care. A systematic review assessed induction and maintenance regimens as well as antibody removal strategies, with statements subjected to the Delphi methodology. A Likert-scale survey was distributed to 53 European experts (Nephrologists, Transplant surgeons and Immunologists) with experience in kidney transplant recipient care. A rate ≥75% with the same answer was considered consensus. Consensus was achieved in 95.3% of statements. While most recommendations aligned, two statements related to complement inhibitors for AMR prophylaxis lacked consensus. The ENGAGE consensus presents contemporary recommendations for desensitization and immunomodulation strategies, grounded in predefined risk categories. The adoption of tailored, patient-specific measures is anticipated to streamline the care of sensitized recipients undergoing renal allografts. While this approach holds the promise of enhancing transplant accessibility and fostering long-term success in transplantation outcomes, its efficacy will need to be assessed through dedicated studies.


Subject(s)
Consensus , Delphi Technique , Graft Rejection , Kidney Transplantation , Humans , Graft Rejection/prevention & control , Graft Rejection/immunology , Europe , Isoantibodies/immunology , Transplant Recipients
3.
HLA ; 103(4): e15458, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38597238

ABSTRACT

We report data on six kidney or heart recipients who were administered daratumumab to treat or prevent antibody-mediated rejection (ABMR). To date, data are scarce concerning the use of daratumumab in solid organ transplantation and most reports show a decrease in donor-specific antigen (DSA) levels and an improvement in ABMR using a multiple myeloma daratumumab administration scheme, that is, with sequential systematic administration. Here, we report on the efficacy of daratumumab 1/ in reducing the histological signs of ABMR, 2/ in reducing the ability of DSA to bind to donor cells in vitro through negativation of flow cytometry crossmatching, 3/ in preferentially being directed towards antibodies sharing epitopes, suggesting that daratumumab may specifically target activated plasma cells, 4/ and when administered as a single dose. This last point suggests, for the first time, that, as for rituximab in auto-immune diseases, the scheme for daratumumab administration could be different for targeting DSA-producing plasma cells than for tumour cells.


Subject(s)
Antibodies, Monoclonal , Kidney Transplantation , Humans , Alleles , Antibodies, Monoclonal/therapeutic use , Graft Rejection , HLA Antigens , Isoantibodies , Kidney , Transplant Recipients
4.
Nat Commun ; 15(1): 3361, 2024 Apr 18.
Article in English | MEDLINE | ID: mdl-38637524

ABSTRACT

Xenotransplantation represents a possible solution to the organ shortage crisis and is an imminent clinical reality with long-term xenograft survival in pig-to-nonhuman primate (NHP) heart and kidney large animal models, and short-term success in recent human decedent and clinical studies. However, concerns remain about safe clinical translation of these results, given the inconsistency in published survival as well as key differences between preclinical procurement and immunosuppression and clinical standards-of-care. Notably, no studies of solid organ pig-to-NHP transplantation have achieved xenograft survival longer than one month without CD40/CD154 costimulatory blockade, which is not currently an FDA-approved immunosuppression strategy. We now present consistent survival in consecutive cases of pig-to-NHP kidney xenotransplantation, including long-term survival after >3 hours of xenograft cold preservation time as well as long-term survival using FDA-approved immunosuppression. These data provide critical supporting evidence for the safety and feasibility of clinical kidney xenotransplantation. Moreover, long-term survival without CD40/CD154 costimulatory blockade may provide important insights for immunosuppression regimens to be considered for first-in-human clinical trials.


Subject(s)
Graft Survival , Kidney , Animals , Humans , Swine , Transplantation, Heterologous/methods , Heterografts , Immunosuppression Therapy/methods , CD40 Ligand , CD40 Antigens , Graft Rejection
5.
World J Gastroenterol ; 30(13): 1791-1800, 2024 Apr 07.
Article in English | MEDLINE | ID: mdl-38659486

ABSTRACT

Liver transplantation (LT) has become the most efficient treatment for pediatric and adult end-stage liver disease and the survival time after transplantation is becoming longer due to the development of surgical techniques and perioperative management. However, long-term side-effects of immunosuppressants, like infection, metabolic disorders and malignant tumor are gaining more attention. Immune tolerance is the status in which LT recipients no longer need to take any immunosuppressants, but the liver function and intrahepatic histology maintain normal. The approaches to achieve immune tolerance after transplantation include spontaneous, operational and induced tolerance. The first two means require no specific intervention but withdrawing immunosuppressant gradually during follow-up. No clinical factors or biomarkers so far could accurately predict who are suitable for immunosuppressant withdraw after transplantation. With the understanding to the underlying mechanisms of immune tolerance, many strategies have been developed to induce tolerance in LT recipients. Cellular strategy is one of the most promising methods for immune tolerance induction, including chimerism induced by hematopoietic stem cells and adoptive transfer of regulatory immune cells. The safety and efficacy of various cell products have been evaluated by prospective preclinical and clinical trials, while obstacles still exist before translating into clinical practice. Here, we will summarize the latest perspectives and concerns on the clinical application of cellular strategies in LT recipients.


Subject(s)
Immunosuppressive Agents , Liver Transplantation , Humans , Liver Transplantation/adverse effects , Liver Transplantation/methods , Immunosuppressive Agents/therapeutic use , Immunosuppressive Agents/adverse effects , Hematopoietic Stem Cell Transplantation/adverse effects , Hematopoietic Stem Cell Transplantation/methods , Immune Tolerance/immunology , End Stage Liver Disease/surgery , End Stage Liver Disease/immunology , Graft Rejection/immunology , Graft Rejection/prevention & control , Transplantation Tolerance/immunology , Adoptive Transfer/methods , Graft Survival/immunology , Graft Survival/drug effects , Animals , Treatment Outcome , T-Lymphocytes, Regulatory/immunology , Liver/immunology , Liver/pathology , Liver/surgery
6.
Front Immunol ; 15: 1389105, 2024.
Article in English | MEDLINE | ID: mdl-38660296

ABSTRACT

Background: Progressive decline of allograft function leads to premature graft loss. Forkhead box P3 (FOXP3), a characteristic gene of T-regulatory cells, is known to be essential for auto-antigen tolerance. We assessed the hypothesis that low FOXP3 mRNA splice variant levels in peripheral blood cells early after transplantation are associated with progressive allograft injury. Methods: Blood samples were prospectively collected from 333 incident kidney transplant recipients on the first and 29th postoperative day. We used quantitative polymerase chain reaction to determine transcripts of 3 isotypes of FOXP3 splice variants, including pre-mature FOXP3 and full length FOXP3 (FOXP3fl). We investigated the association between FOXP3 splice variant levels and the declines in estimated glomerular filtration rate (eGFR) of more than 5ml/min/1.73m2 within the first-year post-transplant using logistic regression. Results: We observed lower FOXP3fl levels in recipients with declining eGFR (N = 132) than in recipients with stable eGFR (N = 201), (logarithmic value -4.13 [IQR -4.50 to -3.84] vs -4.00 [4.32 to -3.74], p=0.02). In ad hoc analysis pre-transplant FOXP3fl levels were similar in both groups. The association between FOXP3fl and declining eGFR was confirmed by multivariable analysis adjusted for potential confounding factors (Odds Ratio 0.51, 95% confidence interval 0.28 to 0.91: p=0.02). When stratifying FOXP3fl levels into quartiles, recipients with lower day1 FOXP3fl had the highest rate of declining eGFR (p=0.04). Conclusion: Low FOXP3fl splice variant levels at the first postoperative day in kidney transplant recipients were associated with severe decline of eGFR, a well-known surrogate for hard endpoints.


Subject(s)
Forkhead Transcription Factors , Kidney Transplantation , Protein Isoforms , Transplantation Tolerance , Kidney Transplantation/adverse effects , Humans , Forkhead Transcription Factors/genetics , Male , Female , Middle Aged , Transplantation Tolerance/genetics , Adult , Protein Isoforms/genetics , Glomerular Filtration Rate , Graft Rejection/immunology , Graft Rejection/genetics , Allografts/immunology , Alternative Splicing , Aged
7.
Stem Cell Res Ther ; 15(1): 111, 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38644499

ABSTRACT

BACKGROUND: Graft failure (GF) is a rare but serious complication after allogeneic hematopoietic stem cell transplantation (HSCT). Prevention of graft failure remains the most advisable approach as there is no clear recommendation for the best strategies for reversing this complication. Administration of growth factor, additional hematopoietic progenitor boost, or a salvage HSCT are current modalities recommended for the treatment of GF. Autologous recovery without evidence of disease relapse occurs rarely in patients with GF, and in the absence of autologous recovery, further salvage transplantation following a second conditioning regimen is a potential treatment option that offers the best chances of long-term disease-free survival. The preconditioning regimens of second HSCT have a significant impact on engraftment and outcome, however, currently there is no consensus on optimal conditioning regimen for second HSCT in patients who have developed GF. Furthermore, a second transplant from a different donor or the same donor is still a matter of debate. OBSERVATIONS: We present our experience in managing pediatric patients with acute leukemia who encountered graft failure following stem cell transplantation. CONCLUSIONS AND RELEVANCE: Although a second transplantation is almost the only salvage method, we illustrate that some pediatric patients with acute leukemia who experience graft failure after an allogeneic stem cell transplant using Myeloablative conditioning (MAC) regimen may achieve long-term disease-free survival through autologous hematopoiesis recovery.


Subject(s)
Hematopoietic Stem Cell Transplantation , Transplantation Conditioning , Humans , Hematopoietic Stem Cell Transplantation/methods , Hematopoietic Stem Cell Transplantation/adverse effects , Child , Female , Male , Transplantation Conditioning/methods , Child, Preschool , Transplantation, Homologous/methods , Adolescent , Graft Rejection , Acute Disease , Transplantation, Autologous , Infant , Leukemia, Myeloid, Acute/therapy
8.
Transpl Int ; 37: 11878, 2024.
Article in English | MEDLINE | ID: mdl-38644935

ABSTRACT

The effect of changes in immunosuppressive therapy during the acute phase post-heart transplantation (HTx) on clinical outcomes remains unclear. This study aimed to investigate the effects of changes in immunosuppressive therapy by corticosteroid (CS) weaning and everolimus (EVR) initiation during the first year post-HTx on clinical outcomes. We analyzed 622 recipients registered in the Korean Organ Transplant Registry (KOTRY) between January 2014 and December 2021. The median age at HTx was 56 years (interquartile range [IQR], 45-62), and the median follow-up time was 3.9 years (IQR 2.0-5.1). The early EVR initiation within the first year post-HTx and maintenance during the follow-up is associated with reduced the risk of primary composite outcome (all-cause mortality or re-transplantation) (HR, 0.24; 95% CI 0.09-0.68; p < 0.001) and cardiac allograft vasculopathy (CAV) (HR, 0.39; 95% CI 0.19-0.79; p = 0.009) compared with EVR-free or EVR intermittent treatment regimen, regardless of CS weaning. However, the early EVR initiation tends to increase the risk of acute allograft rejection compared with EVR-free or EVR intermittent treatment.


Subject(s)
Adrenal Cortex Hormones , Everolimus , Graft Rejection , Heart Transplantation , Immunosuppressive Agents , Registries , Humans , Everolimus/administration & dosage , Everolimus/therapeutic use , Heart Transplantation/adverse effects , Middle Aged , Male , Female , Immunosuppressive Agents/therapeutic use , Immunosuppressive Agents/administration & dosage , Republic of Korea/epidemiology , Graft Rejection/prevention & control , Adrenal Cortex Hormones/administration & dosage , Adrenal Cortex Hormones/therapeutic use , Treatment Outcome , Graft Survival , Retrospective Studies
9.
Front Immunol ; 15: 1360627, 2024.
Article in English | MEDLINE | ID: mdl-38646525

ABSTRACT

Background: Repeated exposure to sensitizing events can activate HLA-specific memory B cells, leading to the production of donor-specific memory B cell antibodies (DSAm) that pose a risk for antibody-mediated rejection (ABMR) in kidney transplant recipients (KTRs). This single-center retrospective study aimed to identify DSAm and assess their association with outcomes in a cohort of KTRs with pretransplant serum donor-specific antibodies (DSA). Methods: We polyclonally activated pretransplant peripheral blood mononuclear cells (PBMCs) from 60 KTRs in vitro, isolated and quantified IgG from the culture supernatant using ELISA, and analyzed the HLA antibodies of eluates with single antigen bead (SAB) assays, comparing them to the donor HLA typing for potential DSAm. Biopsies from 41 KTRs were evaluated for rejection based on BANFF 2019 criteria. Results: At transplantation, a total of 37 DSAm were detected in 26 of 60 patients (43%), of which 13 (35%) were found to be undetectable in serum. No significant association was found between pretransplant DSAm and ABMR (P=0.53). Similar results were observed in a Kaplan-Meier analysis for ABMR within the first year posttransplant (P=0.29). Additionally, MFI levels of DSAm showed no significant association with ABMR (P=0.28). Conclusion: This study suggests no significant association between DSAm and biopsy-proven clinical ABMR. Further prospective research is needed to determine whether assessing DSAm could enhance existing immunological risk assessment methods for monitoring KTRs, particularly in non-sensitized KTRs.


Subject(s)
Graft Rejection , HLA Antigens , Isoantibodies , Kidney Transplantation , Humans , Kidney Transplantation/adverse effects , Retrospective Studies , Male , Female , Middle Aged , Graft Rejection/immunology , Isoantibodies/immunology , Isoantibodies/blood , Adult , HLA Antigens/immunology , Memory B Cells/immunology , Tissue Donors , Aged , Transplant Recipients , Graft Survival/immunology
10.
Transpl Int ; 37: 12556, 2024.
Article in English | MEDLINE | ID: mdl-38650846

ABSTRACT

Macrophages contribute to post-transplant lung rejection. Disulfiram (DSF), an anti-alcoholic drug, has an anti-inflammatory effect and regulates macrophage chemotactic activity. Here, we investigated DSF efficacy in suppressing acute rejection post-lung transplantation. Male Lewis rats (280-300 g) received orthotopic left lung transplants from Fisher 344 rats (minor histocompatibility antigen-mismatched transplantation). DSF (0.75 mg/h) monotherapy or co-solvent only (50% hydroxypropyl-ß-cyclodextrin) as control was subcutaneously administered for 7 days (n = 10/group). No post-transplant immunosuppressant was administered. Grades of acute rejection, infiltration of immune cells positive for CD68, CD3, or CD79a, and gene expression of monocyte chemoattractant protein and pro-inflammatory cytokines in the grafts were assessed 7 days post-transplantation. The DSF-treated group had significantly milder lymphocytic bronchiolitis than the control group. The infiltration levels of CD68+ or CD3+ cells to the peribronchial area were significantly lower in the DSF than in the control groups. The normalized expression of chemokine ligand 2 and interleukin-6 mRNA in allografts was lower in the DSF than in the control groups. Validation assay revealed interleukin-6 expression to be significantly lower in the DSF than in the control groups. DSF can alleviate acute rejection post-lung transplantation by reducing macrophage accumulation around peripheral bronchi and suppressing pro-inflammatory cytokine expression.


Subject(s)
Disulfiram , Graft Rejection , Lung Transplantation , Macrophages , Rats, Inbred F344 , Rats, Inbred Lew , Animals , Lung Transplantation/adverse effects , Graft Rejection/prevention & control , Graft Rejection/immunology , Male , Disulfiram/pharmacology , Disulfiram/therapeutic use , Rats , Macrophages/drug effects , Macrophages/metabolism , Allografts , Antigens, CD/metabolism , Antigens, Differentiation, Myelomonocytic/metabolism , Chemokine CCL2/metabolism , Lung/pathology , Lung/drug effects
11.
Front Immunol ; 15: 1372862, 2024.
Article in English | MEDLINE | ID: mdl-38650942

ABSTRACT

Balancing the immune response after solid organ transplantation (SOT) and vascularized composite allotransplantation (VCA) remains an ongoing clinical challenge. While immunosuppressants can effectively reduce acute rejection rates following transplant surgery, some patients still experience recurrent acute rejection episodes, which in turn may progress to chronic rejection. Furthermore, these immunosuppressive regimens are associated with an increased risk of malignancies and metabolic disorders. Despite significant advancements in the field, these IS related side effects persist as clinical hurdles, emphasizing the need for innovative therapeutic strategies to improve transplant survival and longevity. Cellular therapy, a novel therapeutic approach, has emerged as a potential pathway to promote immune tolerance while minimizing systemic side-effects of standard IS regiments. Various cell types, including chimeric antigen receptor T cells (CAR-T), mesenchymal stromal cells (MSCs), regulatory myeloid cells (RMCs) and regulatory T cells (Tregs), offer unique immunomodulatory properties that may help achieve improved outcomes in transplant patients. This review aims to elucidate the role of cellular therapies, particularly MSCs, T cells, Tregs, RMCs, macrophages, and dendritic cells in SOT and VCA. We explore the immunological features of each cell type, their capacity for immune regulation, and the prospective advantages and obstacles linked to their application in transplant patients. An in-depth outline of the current state of the technology may help SOT and VCA providers refine their perioperative treatment strategies while laying the foundation for further trials that investigate cellular therapeutics in transplantation surgery.


Subject(s)
Organ Transplantation , Humans , Organ Transplantation/adverse effects , Animals , Cell- and Tissue-Based Therapy/methods , Graft Rejection/immunology , Graft Rejection/prevention & control , Immunomodulation
12.
Kidney Int ; 105(5): 921-922, 2024 May.
Article in English | MEDLINE | ID: mdl-38642988

ABSTRACT

Because of the global shortage of donor kidneys, xenotransplantation emerges as a potential solution for individuals with kidney failure who face challenges in securing a suitable donor kidney. A study featured in this month's issue of Kidney International assesses the kidney physiology of a porcine kidney transplanted into a brain-dead human with kidney failure, demonstrating life-sustaining physiological function for 7 days. Together with preclinical nonhuman primate studies, decedent models provide complementary data for development of clinical kidney xenotransplantation.


Subject(s)
Kidney Transplantation , Renal Insufficiency , Humans , Animals , Swine , Kidney Transplantation/adverse effects , Kidney/physiology , Transplantation, Heterologous , Tissue Donors , Graft Rejection , Animals, Genetically Modified
13.
Clin Transplant ; 38(4): e15307, 2024 04.
Article in English | MEDLINE | ID: mdl-38567897

ABSTRACT

BACKGROUND: The use of induction immunosuppression for heart transplantation (HT) is debated given the uncertain benefit and potential risks of infection and malignancy. METHODS: This is a retrospective single-center analysis of 475 consecutive HT recipients from 2003 to 2020 grouped by use of induction with basiliximab group (BG) and the no basiliximab group (NBG). Subgroup analysis by era compared pre-2016 standard-basiliximab (BX) induction and 2016-2020 with selective-BX use as part of a calcineurin-inhibitor-sparing regimen. RESULTS: When adjusted for confounders (sex, age, PRA, eGFR), the BG was less likely to have acute cellular rejection (ACR) (OR.42, p < .001), but had more antibody mediated rejection (AMR) (OR 11.7, p < .001) and more cardiac allograft vasculopathy (CAV) (OR 3.8, p = .04). There was no difference between BG and NBG in the incidence of malignancies or infections. When stratified by era (pre-2016 vs. 2016-2020), ACR remained less common in the BG than the NBG (36% vs. 50%, p = .045) groups, while AMR remained more common (9.7 vs. 0% p = .005). There was no significant difference in conditional survival comparing pre-and post-2016 NBG (HR 2.20 (95% CI.75-6.43); however, both pre-2016 BG and post-2016 BG have significantly higher mortality (HR 2.37 [95% CI 1.02-5.50) and HR 2.69 (95% CI 1.08-6.71), p = .045 and.03, respectively]. CONCLUSION: Basiliximab reduces the incidence of ACR but increases the risk of AMR, CAV, and may be associated with increased mortality. Mechanistic studies are needed to describe a potential T-cell-escape mechanism with enhanced humoral immunity.


Subject(s)
Heart Transplantation , Neoplasms , Humans , Basiliximab/therapeutic use , Immunosuppressive Agents/therapeutic use , Immunosuppressive Agents/pharmacology , Antibodies, Monoclonal/therapeutic use , Retrospective Studies , Graft Rejection/drug therapy , Graft Rejection/etiology , Heart Transplantation/adverse effects , Recombinant Fusion Proteins/therapeutic use
14.
Ren Fail ; 46(1): 2336126, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38627208

ABSTRACT

AIM: Kidney transplant recipients (KTRs), due to their immunosuppressed status, are potentially more susceptible to both the severe effects of COVID-19 and complications in their transplanted organ. The aim of this study is to investigate whether COVID-19 infection increases the risk of rejection in kidney transplant recipients (KTRs). METHODS: This study involved a detailed literature review, conducted using PubMed, with the search being completed by September 7th, 2023. The search strategy incorporated a combination of relevant keywords: 'COVID', 'Renal', 'Kidney', 'Transplant', and 'Rejection'. The results from controlled and uncontrolled studies were separately collated and analyzed. RESULTS: A total of 11 studies were identified, encompassing 1,179 patients. Among these, two controlled studies reported the incidence of rejection in KTRs infected with COVID-19. Pooling data from these studies revealed no significant statistical correlation between COVID-19 infection and biopsy-proven rejection (p = 0.26). In addition, nine non-controlled studies were found, with rejection incidences ranging from 0% to 66.7%. The majority of these studies (eight out of nine) had small sample sizes, ranging from 3 to 75 KTRs, while the largest included 372 KTRs. The combined rejection rate across these studies was calculated to be 11.8%. CONCLUSION: In conclusion, the limited number of published controlled studies revealed no statistically significant association between COVID-19 infection and biopsy-proven rejection among KTRs. However, the broader analysis of non-controlled studies showed a variable rejection incidence with a pooled rejection rate of 11.8%. There is insufficient high-quality data to explore the association of COVID-19 infection and rejection.


Subject(s)
COVID-19 , Kidney Transplantation , Humans , Kidney Transplantation/adverse effects , Immunosuppressive Agents/adverse effects , COVID-19/complications , Kidney , Allografts , Graft Rejection , Transplant Recipients
15.
Clin Transplant ; 38(4): e15314, 2024 04.
Article in English | MEDLINE | ID: mdl-38628057

ABSTRACT

Kidney transplantation is a highly effective treatment for end-stage kidney disease. However, allograft rejection remains a significant clinical challenge in kidney transplant patients. Although kidney allograft biopsy is the gold-standard diagnostic method, it is an invasive procedure. Since the current monitoring methods, including screening of serum creatinine and urinary protein, are not of sufficient sensitivity, there is a need for effective post-transplant monitoring to detect allograft rejection at an early stage. Extracellular vesicles are vesicles with a lipid bilayer that originate from different cell types in pathological and physiological conditions. The content of extracellular vesicles reflects the status of cells at the time of their production. This review comprehensively summarizes clinical, in vivo, and in vitro reports that highlight the potential of extracellular vesicles as diagnostic biomarkers for kidney allograft rejection. Clarification would facilitate differentiation between rejection and non-rejection and identification of the mechanisms involved in the allograft rejection. Despite increasing evidence, further research is necessary to establish the clinical utility of extracellular vesicles in the diagnosis and monitoring of allograft rejection in kidney transplant recipients. Using extracellular vesicles as non-invasive biomarkers for diagnosis of kidney allograft rejection could have tremendous benefits in improving patient outcomes and reduce the need for invasive procedures.


Subject(s)
Extracellular Vesicles , Kidney , Humans , Kidney/pathology , Transplantation, Homologous , Biomarkers/urine , Allografts , Graft Rejection/diagnosis , Graft Rejection/etiology
16.
Nephrol Ther ; 20(2): 1-17, 2024 04 04.
Article in French | MEDLINE | ID: mdl-38567520

ABSTRACT

Introduction: Medication non-adherence is a global concern, particularly in the context of renal transplantation, where it leads to graft failures, increased hospitalizations, diminished quality of life for patients, and higher healthcare costs. The aim of this study was to assess the level of therapeutic adherence among Algerian kidney transplant recipients and identify potential influencing factors. Methods: A descriptive, cross-sectional bicenter study was conducted among kidney transplant patients receiving outpatient care at two specialized medical centers in Algeria: the Urology Department of the Hospital Establishment for Urology, Nephrology, and Renal Transplantation in Constantine, and the Nephrology and Renal Transplantation Department of the University Hospital Center (CHU) in Blida, spanning from January to December 2022. Therapeutic adherence was assessed using the 8-item Morisky questionnaire, while the level of knowledge was analyzed through a 12-item questionnaire. Logistic regression was used to identify factors associated with non-adherence to therapy. Results: This study included 130 patients with an average age of 47 years and a sex ratio of 1.7. The results revealed therapeutic non-adherence in 40.8% of the patients. Multivariate analysis identified several potentially associated factors, including residence, unemployment status, lack of affiliation with a health insurance fund, the use of a therapeutic regimen involving triple therapy, the occurrence of adverse effects, limited education level, and insufficient disease knowledge. Furthermore, non-adherence was associated with an increased risk of graft rejection. Conclusion: The findings of this study highlight concerning therapeutic adherence among kidney transplant recipients, emphasizing the crucial importance of therapeutic education to improve treatment adherence and underscoring the need to integrate these factors into clinical patient management.


Introduction: La non-observance thérapeutique est un problème mondial préoccupant, notamment dans le contexte de la transplantation rénale où elle entraîne des échecs de greffe, une augmentation des hospitalisations, une détérioration de la qualité de vie des patients et des coûts de santé accrus. Cette étude avait pour objectif d'évaluer le niveau d'observance thérapeutique chez les transplantés rénaux algériens et d'identifier les facteurs qui pourraient l'influencer. Méthodes: Une étude descriptive transversale bicentrique a été menée auprès de patients transplantés rénaux suivis en ambulatoire dans deux centres médicaux spécialisés en Algérie : le service d'urologie de l'Établissement hospitalier spécialisé (EHS) en urologie, néphrologie et transplantation rénale de Constantine ainsi que le service de néphrologie et transplantation rénale du Centre hospitalier universitaire (CHU) de Blida, sur une période allant de janvier à décembre 2022. L'observance thérapeutique a été évaluée à l'aide du questionnaire à 8 items de Morisky, tandis que le niveau de connaissance a été analysé à travers un questionnaire de 12 items. La régression logistique a été utilisée pour identifier les facteurs associés à la non-observance thérapeutique. Résultats: Cette étude a inclus 130 patients présentant un âge moyen de 47 ans et un sex ratio de 1,7. Les résultats ont révélé une non-observance thérapeutique chez 40,8 % des patients. L'analyse multivariée a permis d'identifier plusieurs facteurs potentiellement associés à cette non-observance, notamment le lieu d'habitation, le statut de chômage, l'absence d'affiliation à une caisse d'assurance maladie, l'utilisation d'un schéma thérapeutique incluant une trithérapie, la survenue d'effets indésirables, le niveau d'éducation limité et une connaissance insuffisante de la maladie. En outre, la non-observance a été associée à un risque accru de rejet de greffe. Conclusion: Les résultats de cette étude révèlent une observance thérapeutique préoccupante chez les transplantés rénaux, soulignant l'importance cruciale de l'éducation thérapeutique afin de l'améliorer et mettant en évidence la nécessité d'intégrer ces facteurs dans la gestion clinique des patients.


Subject(s)
Kidney Transplantation , Humans , Middle Aged , Kidney Transplantation/methods , Cross-Sectional Studies , Algeria , Quality of Life , Medication Adherence , Treatment Adherence and Compliance , Immunosuppressive Agents/therapeutic use , Graft Rejection
17.
J Transl Med ; 22(1): 324, 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38566098

ABSTRACT

The shortage of organs for transplantation emphasizes the urgent need for alternative solutions. Xenotransplantation has emerged as a promising option due to the greater availability of donor organs. However, significant hurdles such as hyperacute rejection and organ ischemia-reperfusion injury pose major challenges, largely orchestrated by the complement system, and activated immune responses. The complement system, a pivotal component of innate immunity, acts as a natural barrier for xenotransplantation. To address the challenges of immune rejection, gene-edited pigs have become a focal point, aiming to shield donor organs from human immune responses and enhance the overall success of xenotransplantation. This comprehensive review aims to illuminate strategies for regulating complement networks to optimize the efficacy of gene-edited pig xenotransplantation. We begin by exploring the impact of the complement system on the effectiveness of xenotransplantation. Subsequently, we delve into the evaluation of key complement regulators specific to gene-edited pigs. To further understand the status of xenotransplantation, we discuss preclinical studies that utilize gene-edited pigs as a viable source of organs. These investigations provide valuable insights into the feasibility and potential success of xenotransplantation, offering a bridge between scientific advancements and clinical application.


Subject(s)
Gene Editing , Tissue and Organ Procurement , Humans , Animals , Swine , Transplantation, Heterologous , Animals, Genetically Modified , Graft Rejection/genetics
19.
Xenotransplantation ; 31(2): e12859, 2024.
Article in English | MEDLINE | ID: mdl-38646924

ABSTRACT

Antibody-mediated rejection (AMR) is a common cause of graft failure after pig-to-nonhuman primate organ transplantation, even when the graft is from a pig with multiple genetic modifications. The specific factors that initiate AMR are often uncertain. We report two cases of pig kidney transplantation into immunosuppressed baboons in which we identify novel factors associated with the initiation of AMR. In the first, membranous nephropathy was the initiating factor that was then associated with the apparent loss of the therapeutic anti-CD154 monoclonal antibody in the urine when severe proteinuria was present. This observation suggests that proteinuria may be associated with the loss of any therapeutic monoclonal antibody, for example, anti-CD154 or eculizumab, in the urine, resulting in xenograft rejection. In the second case, the sequence of events and histopathology tentatively suggested that pyelonephritis may have initiated acute-onset AMR. The association of a urinary infection with graft rejection has been well-documented in ABO-incompatible kidney allotransplantation based on the expression of an antigen on the invading microorganism shared with the kidney graft, generating an immune response to the graft. To our knowledge, these potential initiating factors of AMR in pig xenografts have not been highlighted previously.


Subject(s)
Graft Rejection , Heterografts , Immunosuppressive Agents , Kidney Transplantation , Papio , Transplantation, Heterologous , Animals , Graft Rejection/immunology , Kidney Transplantation/adverse effects , Kidney Transplantation/methods , Transplantation, Heterologous/methods , Transplantation, Heterologous/adverse effects , Swine , Heterografts/immunology , Immunosuppression Therapy/methods , Female , Humans , Male
20.
Pediatr Transplant ; 28(3): e14761, 2024 May.
Article in English | MEDLINE | ID: mdl-38628086

ABSTRACT

BACKGROUND: Renal transplantation is currently the best treatment option for patients with end-stage renal disease. However, the use of kidneys from donors under 6 years of age as a possibility to increase the organ pool in pediatric recipients remains a controversial matter. We aimed to investigate whether donor age is associated to the long-term functionality of the renal graft. Likewise, we analyzed the adaptation of the graft to the ascending functional requirements in the pediatric patient. METHODS: Retrospective study of the results obtained in pediatric recipients transplanted with grafts from donors between 3 and 6 years of age, comparing them with those of grafts from donors older than 6 years. Among the variables compared are cumulative graft survival, renal size, need for antiproteinuric therapy, GFR, incidence of rejection, pyelonephritis, renal failure and surgical or tumor complications. RESULTS: A total of 43 transplants were performed with donors aged 3-6 years, and 42 transplants with donors older than 6 years. Cumulative graft survival at 5 years was 81% for the younger donor group compared to 98% for the older donor group (p < .05). At 8 years, cumulative graft survival for donors <6 years was 74%. As for the mean estimated graft survival, it was 11.52 years for the younger donor group and 14.51 years for older donors. During follow-up, the younger donor group presented greater renal enlargement and need for antiproteinuric therapy. The older donors group had a higher GFR during the first year of follow-up, which then equalized in both groups. There were no statistically significant differences in the incidence of acute or chronic rejection, acute pyelonephritis, acute renal failure or surgical or tumor complications. CONCLUSIONS: Renal transplants of grafts equal to or less than 6 years old have good short-term and acceptable long-term results in pediatric patients.


Subject(s)
Acute Kidney Injury , Kidney Transplantation , Neoplasms , Pyelonephritis , Child , Humans , Kidney Transplantation/adverse effects , Retrospective Studies , Tissue Donors , Pyelonephritis/etiology , Graft Survival , Acute Kidney Injury/etiology , Graft Rejection/epidemiology , Neoplasms/etiology , Age Factors
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