RESUMEN
BACKGROUND: Antibody-mediated rejection following liver transplantation (LT) has been increasingly recognized, particularly with respect to the emergence of de novo donor-specific antibodies (DSAs) and their impact on graft longevity. While substantial evidence for adult populations exists, research focusing on pediatric LT outcomes remains limited. AIM: To investigate the prevalence of human leukocyte antigen (HLA) mismatches and DSA and evaluate their association with rejection episodes after pediatric LT. METHODS: A cohort of pediatric LT recipients underwent HLA testing at Santa Casa de Porto Alegre, Brazil, between December 2013 and December 2023. Only patients who survived for > 30 days after LT with at least one DSA analysis were included. DSA classes I and II and cross-matches were analyzed. The presence of de novo DSA (dnDSA) was evaluated at least 3 months after LT using the Luminex® single antigen bead method, with a positive reaction threshold set at 1000 MFI. Rejection episodes were confirmed by liver biopsy. RESULTS: Overall, 67 transplanted children were analyzed; 61 received grafts from living donors, 85% of whom were related to recipients. Pre-transplant DSA (class I or II) was detected in 28.3% of patients, and dnDSA was detected in 48.4%. The median time to DSA detection after LT was 19.7 [interquartile range (IQR): 4.3-35.6] months. Biopsy-proven rejection occurred in 13 patients at follow-up, with C4d positivity observed in 5/13 Liver biopsies. The median time to rejection was 7.8 (IQR: 5.7-12.8) months. The presence of dnDSA was significantly associated with rejection (36% vs 3%, P < 0.001). The rejection-free survival rates at 12 and 24 months were 76% vs 100% and 58% vs 95% for patients with dnDSA anti-DQ vs those without, respectively. CONCLUSION: Our findings highlight the importance of incorporating DSA assessment into pre- and post-transplantation protocols for pediatric LT recipients. Future implications may include immunosuppression minimization strategies based on this analysis in pediatric LT recipients.
Asunto(s)
Rechazo de Injerto , Supervivencia de Injerto , Antígenos HLA , Prueba de Histocompatibilidad , Isoanticuerpos , Trasplante de Hígado , Humanos , Trasplante de Hígado/efectos adversos , Masculino , Rechazo de Injerto/inmunología , Rechazo de Injerto/epidemiología , Femenino , Niño , Antígenos HLA/inmunología , Isoanticuerpos/sangre , Isoanticuerpos/inmunología , Brasil/epidemiología , Preescolar , Supervivencia de Injerto/inmunología , Prueba de Histocompatibilidad/métodos , Incidencia , Lactante , Adolescente , Hígado/inmunología , Hígado/patología , Biopsia , Estudios Retrospectivos , Donadores Vivos , Receptores de Trasplantes/estadística & datos numéricosRESUMEN
Background: Despite the growing number of elderly kidney transplant (Ktx) recipients, few studies have examined the effects of immunosuppression on their lymphocyte profiles. Methods: We evaluated the early conversion from mycophenolate sodium (MPS) to everolimus (EVL) after rabbit antithymocyte globulin (rATG) 2 mg/kg induction in elderly kidney recipients. Three groups of KTx patients were compared: (a) Young (n=20, 36 ± 7 y) receiving standard immunosuppression (Group A1) (prednisone, tacrolimus, and MPS), (b) Elderly (n=35, 65 ± 3 y) receiving standard immunosuppression (Group B1), and (c) Elderly (n=16, 65 ± 3 y) with early (mean 30 d) conversion from MPS to EVL (Group B2). Naive, memory, and regulatory peripheral blood TCD4+ lymphocytes were quantified at 0, 30, and 365 d. Results: Results are reported as [mean(p25-p75)]. Young recipients had higher lymphocyte counts at baseline [2,100(1,630-2,400) vs. 1,310 (1,000-1,600)/mm3, p<0.0001] maintained higher counts within 365 d [1,850(1,590-2,120) vs. 1,130(460-1,325)/mm3, p=0.018 and vs. 1,410(805-1,895)/mm3, p=0.268]. Elderly recipients showed a decrease in lymphocytes within 30 d [1,310(1,000-1,600) vs. 910(700-1,198)/mm3, p=0.0012] with recovery within 365 d. The same pattern was observed in total lymphocytes and TCD4+ counts. Rabbit antithymocyte globulin induced a reduction in central memory T-cell percentages at 30 d in both young recipients [6.2(3.77-10.8) vs. 5.32(2.49-7.28)% of CD4+, p=0.036] and in elderly recipients [8.17(5.28-12.88) vs. 6.74(4.36-11)% of CD4+, p=0.05] on standard immunosuppression, returning to baseline at 365 d in elderly recipients but not in young recipients. Regulatory T CD39+ cells (Treg) percentages decreased at 30 d in elderly recipients [2.1(1.23-3.51) vs. 1.69(0.8-2.66)% of CD4+, p=0.0028] and in young recipients [1.29(0.45-1.85) vs. 0.84(0.18-1.82)% of CD4+, p=0.0038], returning to baseline at 365 d in elderly recipients [2.1(1.23-3.51) vs. 2.042(0.88-2.42)% of CD4+], but not in young recipients [1.29(0.45-1.85) vs. 0.86(0.7-1.34) % of CD4+]. The elderly everolimus conversion group did not show significant changes in cell profile over time or compared to elderly recipients with standard immunosuppression. Conclusion: Aging favored the maintenance of Treg during the late transplantation period despite ongoing immunosuppression. Lymphocyte depletion due to rATG was more prominent in elderly recipients and affected memory subsets with a temporary reduction in central memory T cells. However, conversion to everolimus did not impact Treg profile. Reducing the dose of rATG in elderly recipients seems necessary for the expected lymphocyte changes with EVL to occur. Clinical trial registration: nEverOld Trial, identifier NTC01631058.
Asunto(s)
Inmunosupresores , Trasplante de Riñón , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Edad , Suero Antilinfocítico/uso terapéutico , Everolimus , Rechazo de Injerto/inmunología , Rechazo de Injerto/prevención & control , Terapia de Inmunosupresión/métodos , Inmunosupresores/uso terapéutico , Recuento de Linfocitos , Ácido Micofenólico/administración & dosificación , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/efectos de los fármacos , Subgrupos de Linfocitos T/metabolismo , Tacrolimus/administración & dosificación , Tacrolimus/uso terapéutico , Receptores de TrasplantesRESUMEN
INTRODUCTION: The scarcity of suitable donor organs has led to the inclusion of Expanded Criteria Donor (ECD) kidneys to augment the donor pool, despite potential concerns regarding post-transplant outcomes. METHODS: This retrospective study analyzed the clinical outcomes of a cohort of 317 kidney transplant recipients from deceased donors at a single center between 2008 and 2018. Patients were categorized into ECD and Standard Criteria Donor (SCD) groups, with primary nonfunctioning grafts excluded. Comprehensive laboratory evaluations were conducted, including HLA typing and serum creatinine levels. Immunosuppressive regimens were standardized, and statistical analyses were performed using the SPSS program. RESULTS: The sample consisted of 83 (26.18%) patients who received kidney transplants from ECDs and 234 (73.82%) from SCDs. The ECD group showed a longer cold ischemia time (p = 0.019) and a higher rate of delayed graft function (DGF) compared with the SCD group. No significant differences were observed in graft survival (p = 0.370) or patient survival (p = 0.993) between the ECD and SCD groups. However, differences in graft survival were noted between the groups when stratified by DGF status: ECD with DGF vs. ECD without DGF (p = 0.029), ECD with DGF vs. SCD with DGF (p = 0.188), ECD with DGF vs. SCD without DGF (p = 0.022), ECD without DGF vs. SCD with DGF (p = 0.014), ECD without DGF vs. SCD without DGF (p = 0.340), and SCD with DGF vs. SCD without DGF (p = 0.195). No differences in patient survival rates were observed among these groups for all pairwise comparisons (p > 0.05) when stratified by donor criteria and DGF status. CONCLUSIONS: Graft and patient survival rates were comparable between ECD and SCD kidney transplant recipients.
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Supervivencia de Injerto , Trasplante de Riñón , Donantes de Tejidos , Humanos , Femenino , Masculino , Estudios Retrospectivos , Persona de Mediana Edad , Adulto , Funcionamiento Retardado del Injerto , Rechazo de Injerto/mortalidad , Rechazo de Injerto/inmunología , Resultado del Tratamiento , Selección de Donante , Tasa de SupervivenciaRESUMEN
Pediatric solid organ transplant (SOT) recipients face a challenging balance between immunosuppression and graft rejection. While Epstein-Barr Virus (EBV) and cytomegalovirus (HCMV) are known contributors to post-transplant lymphoproliferative disease and graft rejection, respectively, the roles of herpesvirus 6 and 7 (HHV6 and HHV7) and the impact of these herpesviruses on cytokine levels remain unclear, leading to gaps in clinical practice. In this associative study, we measured 17 cytokines using a Bio-Plex assay in a meticulously curated plasma sample pool (N = 158) from pediatric kidney and liver transplant recipients over a one-year follow-up period. The samples included virus-negative and virus-positive cases, either individually or in combination, along with episodes of graft rejection. We observed that the elevation of IL-4, IL-8, and IL-10 correlated with graft rejection. These cytokines were elevated in samples where HCMV or HHV6 were detected alone or where EBV and HHV7 were co-detected. Interestingly, latent EBV, when detected independently, exhibited an immunomodulatory effect by downregulating cytokine levels. However, in co-detection scenarios with ß-herpesviruses, EBV transitioned to a lytic state, also associating with heightened cytokinemia and graft rejection. These findings highlight the complex interactions between the immune response and herpesviruses in transplant recipients. The study advocates for enhanced monitoring of not only EBV and HCMV but also HHV6 and HHV7, providing valuable insights for improved risk assessment and targeted interventions in pediatric SOT recipients.
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Citocinas , Citomegalovirus , Rechazo de Injerto , Herpesvirus Humano 6 , Herpesvirus Humano 7 , Trasplante de Riñón , Trasplante de Hígado , Humanos , Trasplante de Riñón/efectos adversos , Citocinas/sangre , Citocinas/metabolismo , Niño , Herpesvirus Humano 6/inmunología , Masculino , Femenino , Preescolar , Trasplante de Hígado/efectos adversos , Citomegalovirus/inmunología , Rechazo de Injerto/virología , Rechazo de Injerto/inmunología , Herpesvirus Humano 4/inmunología , Adolescente , Lactante , Infecciones por Herpesviridae/virología , Infecciones por Herpesviridae/inmunología , Receptores de Trasplantes , Infecciones por Virus de Epstein-Barr/virología , Infecciones por Virus de Epstein-Barr/inmunología , Infecciones por Citomegalovirus/virología , Infecciones por Citomegalovirus/inmunología , HerpesviridaeRESUMEN
Solid-organ transplantation procedures have witnessed a surge in frequency. Consequently, increased attention to associated infections and their impact on graft success is warranted. The liver is the principal target for infection by the flatworm Schistosoma mansoni. Hence, rigorous screening protocols for this parasite should be implemented for liver transplantation donors and recipients. This study investigated the risks posed by schistosomiasis-infected liver tissues for successful liver transplantation (LT), considering donors and recipients, by analyzing reported cases. Among the 43 patients undergoing LT (donors = 19; recipients = 24), 32 were infected with S. mansoni, five were infected with other Schistosoma species, and no identification was made in four patients. Reported follow-up periods ranged from 1 to 132 months, and all patients achieved successful recovery. As these helminths do not replicate in their vertebrate hosts, immunosuppressive treatment is not expected to promote increased morbidity or reactivation. Moreover, suspected or confirmed schistosomiasis infections often have a benign course, and generally, should not prevent LT. The available literature was reviewed and a provisional screening protocol has been proposed.
Asunto(s)
Trasplante de Hígado , Esquistosomiasis mansoni , Trasplante de Hígado/efectos adversos , Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Animales , Factores de Riesgo , Adulto Joven , Rechazo de Injerto , Donantes de Tejidos , Schistosoma mansoni/aislamiento & purificación , Anciano , Adolescente , Parasitosis HepáticasRESUMEN
Patients with end-stage heart disease who undergo a heart transplant frequently have simultaneous kidney insufficiency, therefore simultaneous heart and kidney transplantation is an option and it is necessary to understand its characteristics and long-term variables. The recipient characteristics and operative and long-term variables were assessed in a meta-analysis. A total of 781 studies were screened, and 33 were thoroughly reviewed. 15 retrospective cohort studies and 376 patients were included. The recipient's mean age was 51.1 years (95% CI 48.52-53.67) and 84% (95% CI 80-87) were male. 71% (95% CI 59-83) of the recipients were dialysis dependent. The most common indication was ischemic cardiomyopathy [47% (95% CI 41-53)] and cardiorenal syndrome [22% (95% CI 9-35)]. Also, 33% (95% CI 20-46) of the patients presented with delayed graft function. During the mean follow-up period of 67.49 months (95% CI 45.64-89.33), simultaneous rejection episodes of both organ allografts were described in 5 cases only. Overall survival was 95% (95% CI 88-100) at 30 days, 81% (95% CI 76-86) at 1 year, 79% (95% CI 71-87) at 3, and 71% (95% CI 59-83) at 5 years. Simultaneous heart and kidney transplantation is an important option for concurrent cardiac and renal dysfunction and has acceptable rejection and survival rates.
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Rechazo de Injerto , Supervivencia de Injerto , Trasplante de Corazón , Trasplante de Riñón , Humanos , Masculino , Persona de Mediana Edad , Femenino , Síndrome Cardiorrenal/cirugía , Funcionamiento Retardado del Injerto , Estudios Retrospectivos , Fallo Renal Crónico/cirugía , Fallo Renal Crónico/complicaciones , Insuficiencia Cardíaca/cirugía , Insuficiencia Cardíaca/mortalidad , Resultado del TratamientoRESUMEN
INTRODUCTION: Obesity is frequent among organ transplant recipients, increasing the risk of acute graft rejection and overall morbimortality. Laparoscopic sleeve gastrectomy (LSG) effectively improves graft survival and associated comorbidities. We first compared 30-d outcomes between chronic immunosuppressed (CI) and nonchronic immunosuppressed (non-CI) patients. Then, between organ transplant and non-organ transplant CI patients who underwent LSG. METHODS: Patients who underwent LSG within the metabolic and bariatric surgery accreditation and quality improvement program 2017-2019 were included. Using 1:1 and 1:4 propensity score matching analysis, the cohorts were matched for 30 characteristics. We then compared 30-d outcomes between CI and non-CI (analysis 1) and between organ transplant and non-organ transplant CI patients who underwent LSG (analysis 2). RESULTS: A total of 486,576 patients were included. The matched cohorts in analysis 1 (n = 8978) and analysis 2 (n = 1152, n = 371) had similar preoperative characteristics. Propensity score matching in analysis 1 showed that patients in the CI group had significantly higher rates of renal complications (0.4% versus 0.2%, P = 0.006), unplanned intensive care unit admission (1.1% versus 0.7%, P = 0.003), blood transfusions (1.1% versus 0.7%, P = 0.003), readmissions (4.6% versus 3.5%, P < 0.001), reoperations (1.4% versus 1.0%, P = 0.033), interventions (1.3% versus 1.0%, P = 0.026), and postoperative bleeding (0.6% versus 0.4%, P = 0.013). In analysis 2, patients with organ transplant CI had a higher rate of pulmonary complications (1.1% versus 0.3%, P = 0.043), renal complications (2.4% versus 0.2%, P < 0.001), blood transfusions (6.5% versus 1.3%, P < 0.001), and readmissions (10.0% versus 4.6%, P < 0.001). CONCLUSIONS: Patients with transplant-related CI who underwent LSG have higher 30-d postoperative complication rates compared to nontransplant-related CI patients; however, there were no differences in terms of mortality, intensive care unit admissions, staple line leaks, or bleeding. LSG is safe and feasible in this high-risk population.
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Gastrectomía , Trasplante de Órganos , Complicaciones Posoperatorias , Humanos , Masculino , Femenino , Gastrectomía/efectos adversos , Persona de Mediana Edad , Adulto , Estudios Retrospectivos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Trasplante de Órganos/efectos adversos , Puntaje de Propensión , Resultado del Tratamiento , Laparoscopía/efectos adversos , Terapia de Inmunosupresión/efectos adversos , Supervivencia de Injerto , Rechazo de Injerto/epidemiología , Rechazo de Injerto/inmunología , Rechazo de Injerto/etiologíaRESUMEN
INTRODUCTION: This study evaluated the efficacy and safety of mycophenolate mofetil (MMF) associated with tacrolimus (TAC) in patients undergoing kidney-pancreas and kidney transplants, in comparison with cyclosporine (CyA), azathioprine (AZA), everolimus (EVL), sirolimus (SRL), manitimus (MAN), mizoribine (MZR), and enteric-coated mycophenolate sodium (ECMPS) in combination or monotherapy. METHODS: A systematic review and meta-analysis of randomized clinical trials was performed. The outcomes comprised acute rejection, graft loss, and adverse events. RESULTS: Thirty studies were included. The main adverse events related to the TAC+MMF scheme were infection (36%; 95%CI: 26%-46%), including cytomegalovirus (CMV) (14%; 95%CI: 8%-20%); anemia (20%; 95%CI: 2%-37%); leukopenia (18%; 95%CI: 3%-33%); nausea (20%; 95%CI: 1%-39%); and diarrhea (26%; 95%CI:13%-40%). TAC+MMF was compared to the schemes AZA+TAC, CyA+AZA, CyA+MMF, CyA+SRL, ECMPS, EVL, MAN+TAC, MMF+SRL, MZR, TAC+AZA, TAC+EVR, TAC+MZR, TAC +SRL and TAC. TAC+MMF was associated with a lower risk of rejection than MMF monotherapy (RD: -0.24; 95%CI -0.46; -0.02). Comparing TAC+MMF with the other regimens, no significant difference was found for graft loss. TAC+MMF was associated with a higher risk of infections than MZR (RD: 0.174; 95%CI: 0.25; 0.323) and TAC monotherapy (RD: 0.07; 95%CI 0.003; 0.138). CONCLUSION: Gastrointestinal and hematological adverse events and infections are the most common with TAC+MMF for kidney-pancreas and kidney. TAC+MMF effectively prevents acute cellular rejection, and alternatives with AZA, CyA, SRL, ECMPS, EVL, MAN, and MSR have similar efficacy and safety profiles. TAC monotherapy and MZR may be associated with a lower risk of infections.
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Inmunosupresores , Trasplante de Riñón , Ácido Micofenólico , Trasplante de Páncreas , Ensayos Clínicos Controlados Aleatorios como Asunto , Tacrolimus , Humanos , Inmunosupresores/uso terapéutico , Inmunosupresores/efectos adversos , Ácido Micofenólico/uso terapéutico , Tacrolimus/uso terapéutico , Quimioterapia Combinada , Rechazo de Injerto/prevención & control , Resultado del TratamientoRESUMEN
Non-adherence to immunosuppressive medication after kidney transplant is an important cause of graft rejection and loss. Approaches to minimization of non-adherence have focused on the identification of episodes of medication non-adherence, but by then irreparable harm to the graft may already have occurred, and a more effective approach would be to adopt preventive measures in patients who may have difficulty in adhering to medication. The aim of this study protocol is to develop and validate a clinical questionnaire for assessing, in kidney transplant candidate patients in the pre-transplant setting, the predisposition to non-adherence to immunosuppressive medication. In this multicenter, prospective study, a pilot questionnaire in Brazilian Portuguese language, composed of Likert-scaled statements expressing patients' beliefs, behaviors and barriers regarding medication taking will be assembled from a literature review, from focus groups, and an expert panel. The pilot questionnaire will be administered to a minimum of 300 patients in kidney transplant waiting lists and exploratory factor analysis will be used for development of the definitive questionnaire. A random subsample of a minimum of 60 patients will have the scale re-administered after one month for evaluation of test-retest reliability. A multicenter, external validation study will include 364 kidney transplant candidates who will be evaluated immediately before surgery and at months 3, 6 and 12 post-transplant for assessment of concurrent validity, by comparison with two scales that assess medication non-adherence, and for determination of predictive validity using a triangulation method for assessment of medication non-adherence. Structural validity will be assessed with confirmatory factor analysis using structural equation modeling. Cross-cultural generalizability and validity will be assessed by a multicenter study, in which a translation of the scale to another language will be administered to kidney transplant candidate patients from a different culture, with a subsample being selected for test-retest. This study will be conducted in Spain with a Spanish translation of the scale.
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Inmunosupresores , Trasplante de Riñón , Cumplimiento de la Medicación , Humanos , Inmunosupresores/uso terapéutico , Encuestas y Cuestionarios , Cumplimiento de la Medicación/estadística & datos numéricos , Estudios Prospectivos , Reproducibilidad de los Resultados , Rechazo de Injerto/prevención & control , Proyectos Piloto , Femenino , MasculinoRESUMEN
Con el advenimiento de nuevas técnicas quirúrgicas y medicaciones inmunosupresoras la sobrevida de los niños trasplantados mejoró, llegando a la adultez. La continuidad de su tratamiento requiere un proceso planificado que permita su tránsito a un sistema de salud orientado al adulto. El objeto de este trabajo es mostrar la transición a centros de adultos en una cohorte de pacientes trasplantados renales en el Hospital Garrahan, describir sus características clínicas y demográficas, su evolución, y oportunidades de mejora implementadas. Debido a cambios médicos y su abordaje desde la interdisciplina, se dividió a la población en tres periodos: era 1 (1988-1999), era 2 (2000-2009), y era 3 (2010- 2023). En la era 1, 179 adolescentes continuaron su atención médica en un centro de adultos, 212 en la era 2 y 201 en la era 3. En la era 1 el seguimiento estaba coordinado por el nefrólogo de cabecera y eran consultados los servicios de Urología, Servicio Social y Salud Mental. En la era 2, se fortaleció el trabajo en interdisciplina y aún más a partir del 2011. Surgieron centros de trasplante de adultos que recibían adolescentes y médicos dedicados a ellos en forma preferencial. En la actualidad la transición comienza a los 12 años y progresa hasta los 18. El modelo implementado es la transición directa, entre el nefrólogo pediatra y el de adultos, con varias consultas secuenciales en ambos centros. Si bien la sobrevida del paciente e injerto mejoraron, el rechazo, asociado a no adherencia, es una asignatura por mejorar (AU)
With the advent of new surgical techniques and immunosuppressive medications, the survival of transplanted children has improved, allowing them to reach adulthood. The continuity of their treatment requires a planned process that facilitates their transition to an adult-oriented healthcare system. The aim of this study was to examine the transition to adult centers in a cohort of renal transplant patients at Garrahan Hospital, describing their clinical and demographic characteristics, their evolution, and the improvement opportunities implemented. Based on medical changes and the interdisciplinary approach, the population was divided into three periods: era 1 (1988- 1999), era 2 (2000-2009), and era 3 (2010-2023). In era 1, 179 adolescents continued their medical care in an adult center, 212 in era 2, and 201 in era 3. In era 1, follow-up was coordinated by the attending nephrologist with consultations from Urology, Social Services, and Mental Health Services. In era 2, interdisciplinary work was strengthened, and even more so since 2011. Adult transplant centers were created to receive adolescents with physicians dedicated to their care on a preferential basis. Currently, the transition begins at 12 years of age and progresses up to 18. The implemented model involves direct transition between the pediatric nephrologist and the adult nephrologist, with several sequential consultations in both centers. Although patient and graft survival have improved, rejection associated with non-adherence remains an area for improvement
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Humanos , Niño , Adolescente , Grupo de Atención al Paciente , Trasplante de Riñón , Resultado del Tratamiento , Transición a la Atención de Adultos/organización & administración , Cuidado de Transición , Cumplimiento y Adherencia al Tratamiento/psicología , Rechazo de Injerto/prevención & control , Supervivencia de Injerto , Estudios Retrospectivos , Estudio ObservacionalRESUMEN
OBJECTIVE: To identify the main predictors for corneal graft failure in patients who underwent retransplantation. METHOD: This is a cross-sectional research with a quantitative and analytical approach, conducted based on data from secondary sources of a Human Eye Tissue Bank (HETB) in Northeast Brazil. Data were collected from the medical charts of all patients transplanted between January 2010 and December 2014. Descriptive statistics were used for the univariate analysis by means of absolute and relative frequencies and means. For the inferential analysis, the chi-square (X²) and the Fisher's Exact tests were used. RESULTS: A total of 241 records were reviewed, representing 258 keratoplasties, of which 27 (10.46%) were retransplantations due to corneal graft failure. Of the total, 55.56% of the individuals were female, with a mean age of 58.56 years, 55.56% of the population was brown, and the highest relative frequency of housing found was in the Central Mesoregion. Of the corneal graft failure cases, 88.89% were due to late failure, 30.77% of cases were classified as pseudophakic and 11.57% as aphakic. Through inferential analysis, a statistical association was obtained among the variable "corneal graft failure" and mesoregion of the state, presence of glaucoma, vascularization, and classification of the eye. CONCLUSION: The prognosis of keratoplasty is of multifactorial nature. Factors such as mesoregion of the State (place of residence), glaucoma, corneal vascularization, and aphakic eyes represent predictors for graft failure in the analyzed sample.
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Trasplante de Córnea , Reoperación , Humanos , Femenino , Persona de Mediana Edad , Masculino , Estudios Transversales , Reoperación/estadística & datos numéricos , Anciano , Adulto , Brasil , Factores de Riesgo , Insuficiencia del Tratamiento , Rechazo de InjertoRESUMEN
INTRODUCTION: The causal relationship between hyperparathyroidism and kidney graft dysfunction remains inconclusive. Applying Bradford-Hill's temporality and consistency causation principles, we assessed the effect of parathyroid hormone (iPTH) on graft histology and eGFR trajectory on kidney transplant recipients (KTRs) with normal time-zero graft biopsies. METHODS: Retrospective cohort study evaluating the effect of hyperparathyroidism on interstitial fibrosis and tubular atrophy (IF/TA) development in 1232 graft biopsies. Pre-transplant hyperparathyroidism was categorized by KDIGO or KDOQI criteria, and post-transplant hyperparathyroidism by iPTH >1× and >2× the URL 1 year after transplantation. RESULTS: We included 325 KTRs (56% female, age 38 ± 13 years, follow-up 4.2 years [IQR: 2.7-5.8]). Based on pre-transplant iPTH levels, 26% and 66% exceeded the KDIGO and KDOQI targets, respectively. There were no significant differences in the development of >25% IF/TA between KTRs with pre-transplant iPTH levels above and within target range according to KDIGO (53% vs. 62%, P = .16, HR.94 [95% CI:.67-1.32]) and KDOQI (60% vs. 60%, P = 1.0, HR 1.19 [95% CI:.88-1.60]) criteria. Similarly, there were no differences when using 1 year post-transplant iPTH cut-offs > 88 pg/mL (58% vs. 64%, P = .33) and > 176 pg/mL (55% vs. 62%, P = .19). After adjusting for confounders, no significant differences were observed in eGFR trajectories among the iPTH strata. CONCLUSION: In young KTRs who received a healthy graft, no association was found between increased pre- and post-transplant iPTH levels and graft dysfunction, as assessed histologically and through eGFR trajectory. The concept of hyperparathyroidism as a risk factor for graft dysfunction in recipients at low risk requires reevaluation.
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Aloinjertos , Tasa de Filtración Glomerular , Rechazo de Injerto , Supervivencia de Injerto , Hiperparatiroidismo , Trasplante de Riñón , Complicaciones Posoperatorias , Humanos , Trasplante de Riñón/efectos adversos , Femenino , Masculino , Estudios Retrospectivos , Adulto , Estudios de Seguimiento , Hiperparatiroidismo/etiología , Hiperparatiroidismo/patología , Pronóstico , Factores de Riesgo , Rechazo de Injerto/etiología , Rechazo de Injerto/patología , Aloinjertos/patología , Complicaciones Posoperatorias/etiología , Pruebas de Función Renal , Fallo Renal Crónico/cirugía , Persona de Mediana Edad , Hormona Paratiroidea/sangreRESUMEN
INTRODUCTION: Although RT has improved the survival of the population with ESRD due to all causes, renal outcomes in SLE are controversial. The objective of this study is to describe the characteristics and evolution of the patients and the kidney transplant in LN, and compare it with patients transplanted for other causes. MATERIALS AND METHODS: Retrospective, observational, analytical, single-center study in which records of patients undergoing nephrotransplantation for LN were analyzed. They were compared with a group of patients transplanted at the same center for other causes of ESRD. RESULTS: 41 patients with kidney transplant due to SLE and 89 transplanted due to other causes of ESRD were registered. Graft loss occurred in 12 (29.26%) patients with LN and 34 (38.2%) patients in the comparison group (p = .428). Only one case (4.8%) presented reactivation of the LN in the graft, without graft loss. Median graft survival was 73.1 months in the LN group and 66.3 months in the comparison group (p = .221). A total of 8 (19.5%) patients with LN and 11 (12.4%) without LN died (p = .42), with infections being the main cause in both groups. There were no statistically significant differences between groups in graft and patient survival. In a sub-analysis of 28 patients with LN with aPL study, 4 thrombotic events were observed, in 3 different patients, in the aPL-positive group. There were no statistically significant differences in terms of causes of graft loss and graft survival (positive aFL 75.7 months vs negative aFL 72.7 months, p= .96). There were also no differences in mortality between the groups (p = .61). CONCLUSION: Patients transplanted for LN did not differ from the control population in terms of graft and patient survival. Infections were the main cause of death, so prophylaxis and vaccination continue to be a fundamental pillar in the prevention of infections in immunocompromised patients.
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Supervivencia de Injerto , Fallo Renal Crónico , Trasplante de Riñón , Nefritis Lúpica , Humanos , Estudios Retrospectivos , Femenino , Nefritis Lúpica/cirugía , Nefritis Lúpica/mortalidad , Nefritis Lúpica/complicaciones , Adulto , Masculino , Argentina/epidemiología , Fallo Renal Crónico/cirugía , Fallo Renal Crónico/mortalidad , Persona de Mediana Edad , Pronóstico , Adulto Joven , Rechazo de Injerto , Resultado del TratamientoAsunto(s)
Everolimus , Inmunosupresores , Trasplante de Riñón , Ácido Micofenólico , Sirolimus , Tacrolimus , Humanos , Everolimus/uso terapéutico , Inmunosupresores/uso terapéutico , Inmunosupresores/efectos adversos , Tacrolimus/uso terapéutico , Ácido Micofenólico/uso terapéutico , Ácido Micofenólico/efectos adversos , Sirolimus/uso terapéutico , Sirolimus/efectos adversos , Rechazo de Injerto/prevención & control , Rechazo de Injerto/inmunología , Resultado del Tratamiento , Persona de Mediana Edad , Femenino , Factores de Tiempo , Masculino , Quimioterapia Combinada , AdultoRESUMEN
Tacrolimus (TAC) is an immunosuppressant drug that prevents organ rejection after transplantation. This drug is transported from cells via P-glycoprotein (ABCB1) and is a metabolic substrate for cytochrome P450 (CYP) 3A enzymes, particularly CYP3A4 and CYP3A5. Several single-nucleotide polymorphisms (SNPs) have been identified in the genes encoding CYP3A4, CYP3A5, and ABCB1, including CYP3A4-392A/G (rs2740574), CYP3A5 6986A/G (rs776746), and ABCB1 3435C/T (rs1045642). This study aims to evaluate the association among CYP3A4-392A/G, CYP3A5-6986A/G, and ABCB1-3435C/T polymorphisms and TAC, serum concentration, and biochemical parameters that may affect TAC pharmacokinetics in Mexican kidney transplant (KT) patients. METHODS: Forty-six kidney transplant recipients (KTR) receiving immunosuppressive treatment with TAC in different combinations were included. CYP3A4, CYP3A5, and ABCB1 gene polymorphisms were genotyped using qPCR TaqMan. Serum TAC concentration (as measured) and intervening variables were assessed. Logistic regression analyses were performed at baseline and after one month to assess the extent of the association between the polymorphisms, intervening variables, and TAC concentration. RESULTS: The GG genotype of CYP3A5-6986 A/G polymorphism is associated with TAC pharmacokinetic variability OR 4.35 (95%CI: 1.13-21.9; p = 0.0458) at one month of evolution; in multivariate logistic regression, CYP3A5-6986GG genotype OR 9.32 (95%CI: 1.54-93.08; p = 0.028) and the use of medications or drugs that increase serum TAC concentration OR 9.52 (95%CI: 1.79-88.23; p = 0.018) were strongly associated with TAC pharmacokinetic variability. CONCLUSION: The findings of this study of the Mexican population showed that CYP3A5-6986 A/G GG genotype is associated with a four-fold increase in the likelihood of encountering a TAC concentration of more than 15 ng/dL. The co-occurrence of the CYP3A5-6986GG genotype and the use of drugs that increase TAC concentration correlates with a nine-fold increased risk of experiencing a TAC at a level above 15 ng/mL. Therefore, these patients have an increased susceptibility to TAC-associated toxicity.
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Subfamilia B de Transportador de Casetes de Unión a ATP , Citocromo P-450 CYP3A , Inmunosupresores , Trasplante de Riñón , Polimorfismo de Nucleótido Simple , Tacrolimus , Humanos , Citocromo P-450 CYP3A/genética , Trasplante de Riñón/efectos adversos , Tacrolimus/sangre , Tacrolimus/farmacocinética , Tacrolimus/administración & dosificación , Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Femenino , Masculino , Polimorfismo de Nucleótido Simple/genética , Adulto , México , Inmunosupresores/farmacocinética , Inmunosupresores/sangre , Inmunosupresores/administración & dosificación , Persona de Mediana Edad , Genotipo , Rechazo de Injerto/genéticaRESUMEN
BACKGROUND: Tacrolimus is the primary calcineurin inhibitor used in immunosuppressive regimens to prevent allograft rejection (AR) after organ transplantation. Recent studies have linked intrapatient variability (IPV) of tacrolimus with AR occurrence and reduced survival, especially in kidney transplant recipients. However, limited data are available on the impact of tacrolimus IPV on adverse outcomes after liver transplantation (LT). AIMS: The aim of this study was to assess the association between tacrolimus IPV using various methodologies with acute AR and long-term patient survival after LT. METHODS: All patients who underwent LT from January 2010 to July 2021 were retrospectively evaluated. Tacrolimus IPV was calculated for each patient using the mean and SD, mean absolute deviation (MAD), coefficient of variation (CV), and time in therapeutic range (TTR). These measures were then compared with AR within the first 24 months after LT and to long-term survival. RESULTS: Out of 234 patients, 32 (13.7%) developed AR and 183 (78.2%) survived, with a mean follow-up of 101 ± 43 months. Tacrolimus IPV, assessed by mean, SD, MAD, and CV, was 8.3 ± 2.1, 2.7 ± 1.3, 32.0% ± 11.7%, and 39.4% ± 15.4%, respectively. There was no statistically significant correlation between Tacrolimus IPV and AR or survival post-LT. CONCLUSIONS: In a large cohort of patients from diverse racial backgrounds, tacrolimus IPV was not associated with clinically relevant outcomes such as AR and survival after LT.
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Rechazo de Injerto , Inmunosupresores , Trasplante de Hígado , Tacrolimus , Humanos , Tacrolimus/uso terapéutico , Masculino , Rechazo de Injerto/prevención & control , Femenino , Inmunosupresores/uso terapéutico , Persona de Mediana Edad , Estudios Retrospectivos , Adulto , AncianoRESUMEN
BACKGROUND: Adverse outcomes affect survival rates in heart transplant (HT) patients. This study aims to evaluate the potential of endomyocardial biopsies (EMB) in predicting adverse outcomes and survivorship in this population. METHODS: We analyzed 952 EMB samples from 107 HT patients (2002-2009) receiving standard cyclosporine, mycophenolate, and prednisone doses. EMBs were assessed for cell rejection, vasculitis, Quilty effect, and eosinophilia patterns. Cell rejection was numerically scored (0R = 0, 1R = 1, 2R = 2, 3R = 3). Other patterns scored 1 for presence, 0 for absence. Scores for each pattern group were averaged per EMB. Biopsies were grouped into predictive (adverse outcomes) and non-predictive (no adverse outcomes). Adverse outcomes were acute rejection (AR) or patient death. Statistical analysis included t-tests (continuous variables), chi-square (categorical variables), and logistic regression (p < 0.05). EMB scores correlated with patient survivorship, analyzed using the Kaplan-Meier method and log-rank test. RESULTS: Of 952 EMBs, 720 were non-predictive, 232 predictive (Fig. 1a). Cell rejection was a significant predictor of AR and mortality (Fig. 1b). Only cell rejection was considered for survivorship, with results in quartiles: Q1 (0-0.43), Q2 (0.44-0.83), Q3 (0.84-1.25), and Q4 (>1.25) (Fig. 1c). CONCLUSION: Among the histological patterns studied, cell rejection can be considered an indicator of adverse outcomes and survivorship rates in HT patients.