Relación entre la compatibilidad del HLA y la pérdida del injerto en trasplante renal de donante cadavérico: Un análisis por propensity score matching en Colombia / Relationship between HLA compatibility and graft loss in renal transplant from a deceased donor: An analysis by propensity score matching in Colombia

Introducción. En Colombia, solo un 24 % de los pacientes en lista recibieron un trasplante renal, la mayoría de donante cadavérico. Para la asignación de órganos se considera el HLA A-B-DR, pero la evidencia reciente sugiere que el HLA A-B no está asociado con los desenlaces del trasplante. El objetivo de este estudio fue evaluar la relevancia del HLA A-B-DR en la sobrevida del injerto de los receptores de trasplante renal. Métodos. Estudio de cohorte retrospectivo que incluyó pacientes trasplantados renales con donante cadavérico en Colombiana de Trasplantes, desde 2008 a 2023. Se aplicó un propensity score matching (PSM) para ajustar las covariables en grupos de comparación por compatibilidad y se evaluó la relación del HLA A-B-DR con la sobrevida del injerto renal por medio de la prueba de log rank y la regresión de Cox. Resultados. Se identificaron 1337 pacientes transplantados renales, de los cuales fueron mujeres un 38,7 %, con mediana de edad de 47 años y de índice de masa corporal de 23,8 kg/m2. Tras ajustar por PSM las covariables para los grupos de comparación, la compatibilidad del HLA A-B no se relacionó significativamente con la pérdida del injerto, con HR de 0,99 (IC95% 0,71-1,37) para HLA A y 0,75 (IC95% 0,55-1,02) para HLA B. Solo la compatibilidad por HLA DR fue significativa para pérdida del injerto con un HR de 0,67 (IC95% 0,46-0,98). Conclusión. Este estudio sugiere que la compatibilidad del HLA A-B no influye significativamente en la pérdida del injerto, mientras que la compatibilidad del HLA DR sí mejora la sobrevida del injerto en trasplante renal con donante cadavérico

Introduction. In Colombia, only 24% of patients on the waiting list received a renal transplant, most of them from cadaveric donors. HLA A-B-DR is considered for organ allocation, but recent evidence suggests that HLA A-B is not associated with transplant outcomes. The objective of this study was to evaluate the relevance of HLA A-B-DR on graft survival in kidney transplant recipients. Methods. Retrospective cohort study that included kidney transplant recipients with a cadaveric donor in Colombiana de Trasplantes from 2008 to 2023. A propensity score matching (PSM) was applied to adjust the covariates in comparison groups for compatibility, and the relationship of HLA A-B-DR with kidney graft survival was evaluated using the log rank test and Cox regression. Results. A total of 1337 kidney transplant patients were identified; of those, 38.7% were female, with median age of 47 years, and BMI 23.8 kg/m2. After adjusting the covariates with PSM for the comparison groups, HLA A-B matching was not significantly related to graft loss, with HR of 0.99 (95% CI 0.71-1.37) and 0.75 (95% CI 0.55-1.02), respectively. Only HLA DR matching was significant for graft loss with an HR of 0.67 (95% CI 0.46-0.98). Conclusions. This study suggests that HLA A-B matching does not significantly influence graft loss, whereas HLA DR matching does improve graft survival in renal transplantation with a cadaveric donor.

Descripción de polimorfismos genéticos en CYP3A5 y MDR-1 y su impacto en el rechazo agudo clínico de pacientes trasplantados de hígado del Hospital San Vicente Fundación Rionegro / Description of genetic polymorphisms in CYP3A5 and MDR-1 and their impact on clinical acute rejection in liver transplant patients at Hospital San Vicente Fundación Rionegro

Introducción. El tacrolimus es un medicamento inmunosupresor ampliamente usado en trasplante hepático, que presenta una gran variabilidad interindividual la cual se considera asociada a la frecuencia de polimorfismos de CYP3A5 y MDR-1. El objetivo de este estudio fue evaluar la frecuencia de los polimorfismos rs776746, rs2032582 y rs1045642 y su asociación con rechazo clínico y toxicidad farmacológica. Métodos. Se incluyeron pacientes inmunosuprimidos con tacrolimus a quienes se les realizó trasplante hepático en el Hospital San Vicente Fundación Rionegro entre 2020 y 2022, con supervivencia mayor a un mes. Se evaluaron las variables clínicas, rechazo agudo y toxicidad farmacológica. Se secuenciaron los genes de estudio mediante PCR, comparando la expresión o no en cada uno de los pacientes. Resultados. Se identificaron 17 pacientes. El 43 % de los pacientes se clasificaron como CYP3A5*1/*1 y CYP3A5*1/*3, entre los cuales se encontró asociación con aumento en la tasa de rechazo agudo clínico, al comparar con los pacientes no expresivos (100 % vs. 44 %, p=0,05); no hubo diferencias en cuanto a la toxicidad farmacológica u otros desenlaces. Se encontró el polimorfismo rs2032582 en un 50 % y el rs1045642 en un 23,5 % de los pacientes, sin embargo, no se identificó asociación con rechazo u otros eventos clínicos. Conclusiones. Se encontró una asociación entre el genotipo CYP3A5*1/*1 y CYP3A5*1/*3 y la tasa de rechazo clínico. Sin embargo, se requiere una muestra más amplia para validar estos datos y plantear modelos de medicina personalizada.

Introduction. Tacrolimus is an immunosuppressive drug widely used in liver transplantation, which presents great interindividual variability which is considered associated with the frequency of CYP3A5 and MDR-1 polymorphisms. The objective of this study was to evaluate the frequency of the rs776746, rs2032582 and rs1045642 polymorphisms and their association with clinical rejection and drug toxicity. Methods. Immunosuppressed patients with tacrolimus who underwent a liver transplant at the Hospital San Vicente Fundación Rionegro between 2020 and 2022 were included, with survival of more than one month. Clinical variables, acute rejection and pharmacological toxicity were evaluated. The study genes were sequenced by PCR, comparing their expression or not in each of the patients. Results. Seventeen patients were identified. 43% of the patients were classified as CYP3A5*1/*1 and CYP3A5*1/*3, among which an association was found with increased rates of clinical acute rejection when compared with non-expressive patients (100% vs. 44%, p=0.05). There were no differences in drug toxicity or other outcomes. The rs2032582 polymorphism was found in 50% and rs1045642 in 23.5% of patients; however, no association with rejection or other clinical events was identified. Conclusions. An association was found between the CYP3A5*1/*1 and CYP3A5*1/*3 genotype and the clinical rejection rate. However, a larger sample is required to validate these data and propose models of personalized medicine.

Prevalencia de Complicaciones clínicas y quirúrgicas en el postrasplante renal inmediato y su impacto a corto plazo en la función renal / Prevalence of clinical and surgical complications in immediate post-renal transplantation and their short-term impact on renal function

INTRODUCCIÓN. La enfermedad renal crónica es definida como la pérdida progresiva, permanente e irreversible de la función renal, uno de los tratamientos es el trasplante renal el mismo que aumenta la calidad de vida de los pacientes que presentan esta patología, sin embargo, a pesar de ser uno de las mejores terapias no está exento de complicaciones especialmente las que se presentan posterior al acto quirúrgico ya que afectan al buen funcionamiento del injerto y afecta la supervivencia del mismo. OBJETIVO. Determinar la prevalencia de complicaciones clínicas y quirúrgicas en el postrasplante renal inmediato con el fin de identificar las principales complicaciones que ocasionan mayor deterioro en la función renal a corto plazo. MATERIAL Y MÉTODOS. Estudio Observacional descriptivo transversal, de pacientes trasplantados que se encuentran en seguimiento desde enero del 2015 hasta diciembre del 2018 en el servicio de Trasplante renal del Hospital de Especialidades Carlos Andrade Marín. La muestra será los 211 pacientes trasplantados de donante cadavérico. Los análisis se realizaron con el paquete estadístico IBM SPSS versión 25, para lo cual se empleó estadísticas descriptivas, utilizando tablas y representando los valores absolutos y relativos de las variables cualitativas, así como medidas de tendencia central y de variabilidad para las variables cuantitativas. RESULTADOS. Se estudiaron 193 pacientes trasplantados de los cuales el 49.66% tuvieron complicaciones, de los mismos el 33.16% fueron complicaciones clínicas y 16,5% complicaciones quirúrgicas; de las clínicas la infección de tracto urinario fueron las más prevalentes con 15%, seguida por el rechazo agudo 6,7%, las infecciones por virus poliomavirus BK fueron un porcentaje de 6,2%, la necrosis tubular aguda el 3,16% terminando con el rechazo hiperagudo en el 1,5% y la toxicidad por calcineurínicos 1,04%. Mientras tanto las complicaciones quirúrgicas las urológicas son las más prevalentes 8,8% seguida por las colecciones liquidas con el 6,74% finalmente la trombosis vascular con el 1,04%. CONCLUSIONES. Las complicaciones más prevalentes son las clínicas vs las quirúrgicas, afectando de igual forma la función renal al año sin diferencia estadísticamente significativa.

INTRODUCTION. Chronic kidney disease is defined as the progressive, permanent and irreversible loss of renal function, one of the treatments is renal transplantation, which increases the quality of life of patients with this pathology, however, despite being one of the best therapies, it is not free of complications, especially those that occur after surgery, since they affect the proper functioning of the graft and affect its survival. OBJECTIVE. To determine the prevalence of clinical and surgical complications in immediate post-renal transplantation in order to identify the main complications that cause greater deterioration in short-term renal function. MATERIAL AND METHODS. Cross-sectional descriptive observational study, of transplanted patients under follow-up from January 2015 to December 2018 in the Renal Transplant service of the Hospital de Especialidades Carlos Andrade Marín. The sample will be the 211 cadaveric donor transplanted patients. The analyses were performed with the IBM SPSS version 25 statistical package, for which descriptive statistics were used, using tables and representing the absolute and relative values of qualitative variables, as well as measures of central tendency and variability for quantitative variables. RESULTS. We studied 193 transplanted patients of whom 49.66% had complications, of which 33. Of the clinical complications, urinary tract infection was the most prevalent with 15%, followed by acute rejection 6.7%, polyomavirus BK infections were 6.2%, acute tubular necrosis 3.16%, ending with hyperacute rejection in 1.5% and calcineurin toxicity 1.04%. Meanwhile, urological surgical complications are the most prevalent 8.8% followed by liquid collections with 6.74% and finally vascular thrombosis with 1.04%. CONCLUSIONS. The most prevalent complications are clinical vs. surgical, affecting renal function at one year with no statistically significant difference.

Analysis of causes of graft loss in 135 kidney transplant recipients / 南方医科大学学报

OBJECTIVE@#To investigate the causes of graft loss in kidney transplant recipients.@*METHODS@#We retrospectively analyzed the clinical data of 135 recipients with graft loss after renal transplantation in the Eighth Medical Center of Chinese PLA General Hospital from January 1, 2002 to January 1, 2022.@*RESULTS@#A total of 135 kidney transplant recipients experienced graft failure. The causes of graft loss included graft rejection (70 cases, 51.8%), death of the recipients with functional graft (37 cases, 27.4%), surgical complications (12 cases, 8.9%), drug toxicity (4 cases, 3.0%), carbapenem-resistant Klebsiella pneumoniae infection (4 cases, 3.0%), polyoma BK virus-related nephropathy (3 cases, 2.2%), primary nonfunctioning kidney (2 cases, 1.5%), recurrence of primary disease (2 cases, 1.5%), and prerenal acute renal failure (1 case, 0.7%).@*CONCLUSION@#The main cause of graft loss after renal transplantation is graft rejection, and the secondary cause is death of the recipient with functional graft, and other reasons can be rare.

Trasplante pulmonar: una perspectiva desde la inmunología / Lung transplantation: a perspective from immunology

Resumen El trasplante pulmonar implica una serie de desafíos, que como lo ha demostrado la historia, no sólo depende de un adecuado desarrollo de técnicas quirúrgicas, sino también de la comprensión de una serie de complejas interacciones inmunológicas celulares y humorales que serán las responsables del tipo de respuesta (innata y/o adquirida) fisiológica y que pudiesen desencadenar las complicaciones asociadas al trasplante (rechazo hiperagudo, agudo o crónico). Cada una de las cuales tiene su potencial prevención y/o tratamiento. El poder conocer esta serie de respuestas, permite al clínico anticiparse a algunos de estos eventos y evitar de mejor forma el daño y las consecuencias que pueden producir en los casos de trasplante pulmonar.

Lung transplantation involves a series of challenges, which as history has shown, depends not only on an adequate development of surgical techniques, but also on the understanding of a series of complex cellular and humoral immunological interactions that will be responsible for the type of physiological response (innate - acquired) and that could trigger the complications associated with transplantation (hyperacute, acute or chronic rejection). Each of which has its potential prevention and treatment. Being able to know this series of responses, allows the clinician to anticipate some of these events and to avoid in a better way the damage and the consequences that can occur in cases of lung transplantation.

Protocolo de inmunosupresión en trasplante hepático: revisión de la literatura / Immunosuppression protocol in liver transplantation: review article

El trasplante de hígado es el último recurso para el tratamiento de hepatopatías. Para evitar el rechazo del injerto se requieren esquemas de inmunosupresión que han ido evolucionando a lo largo de los años. Se realizó una revisión bibliográfica en la base de datos PubMed sobre las terapias inmunosupresoras disponibles para evitar el rechazo del injerto en el trasplante hepático, los esquemas utilizados, efectos adversos, interacciones y sus modificaciones desde la fase de inducción hasta el seguimiento posterior. Se encontró que la inducción habitual es con esteroides o terapia inmunológica clonal. En el mantenimiento, los inhibidores de la calcineurina son los más utilizados, las dosis se deben ajustar según sus niveles séricos y la presencia de efectos adversos como nefrotoxicidad o diabetes. Por otra parte, los inhibidores del mTOR han sido considerados como agentes reductores del riesgo de recidiva de cáncer hepatocelular. Las características del paciente y sus comorbilidades (embarazo, insuficiencia renal, diabetes, sepsis, carcinoma hepatocelular) requieren modificar el tratamiento e individualizarlo

Liver transplantation is the last option for the treatment of liver disease. Immunosuppression schemes are required to avoid graft rejection, which have evolved over the years. A literature review was carried out in PubMed on the immunosuppressive therapies available to avoid graft rejection in liver transplantation, as well as on the schemes used, adverse effects, interactions and their modifications from the induction phase to subsequent follow-up. The usual induction was found to be with steroids or clonal immune therapy. In maintenance, calcineurin inhibitors are the most widely used, and their doses should be adjusted according to their serum levels and the presence of adverse effects such as nephrotoxicity or diabetes. On the other hand, mTOR inhibitors have been considered to reduce the risk of hepatocellular cancer recurrence. The characteristics of the patient and their comorbidities (pregnancy, kidney failure, diabetes, sepsis, hepatocellular carcinoma) require modification and individualization of the treatment.

New surgical maneuver to position the graft in a descemet stripping with automated endothelial keratoplasty surgery / Nova manobra cirúrgica para posicionar o enxerto em cirurgia de ceratoplastia endotelial com desnudamento automatizado da Descemet

ABSTRACT Objective: To describe a new surgical maneuver to position the graft in a Descemet Stripping with Automated Endothelial Keratoplasty (DSAEK) surgery. Methods: Case series. Results: This technique allows a correct repositioning of the graft in a minimally invasive way. Conclusion: This new surgical maneuver was successful in manipulating the graft in DSAEK surgery and therefore might be effective and safe.

RESUMO Objetivo: Descrever uma nova manobra cirúrgica para posicionar o enxerto em uma cirurgia de ceratoplastia endotelial automatizada com desnudamento da Descemet. Métodos: Série de casos. Resultados: A técnica permitiu o correto reposicionamento do enxerto de forma minimamente invasiva. Conclusão: Esta nova manobra cirúrgica foi bem-sucedida para manipular o enxerto na cirurgia ceratoplastia endotelial automatizada com desnudamento da Descemet e, portanto, pode ser eficaz e segura.

Desenlaces a largo plazo en pacientes trasplantados renales con donantes de criterios expandidos: experiencia de 10 años / Long-term outcomes in kidney transplant patients with expanded criteria donors: 10-year experience

Introducción. El trasplante renal es el tratamiento de elección para la enfermedad renal crónica. Debido a la brecha con la disponibilidad de donantes, el uso de criterios expandidos es una opción que busca mejorar la tasa de donación mundial. El objetivo de este estudio fue comparar la sobrevida del injerto y del paciente trasplantado con donante de criterios expandidos versus el donante estándar. Métodos. Cohorte retrospectiva de 1002 pacientes con trasplante renal donde se determinó la sobrevida del injerto renal y del receptor a 10 años después del trasplante. La sobrevida del injerto renal y el receptor fueron estimadas por el método de Kaplan-Meier. Una regresión de Cox fue realizada ajustando el modelo multivariado.Resultados. El análisis incluyó 1002 receptores, con un 18,8 % (n=189) que correspondían al uso de donante de criterios expandidos. El grupo de trasplante renal con donante de criterios expandidos tuvo menor sobrevida del paciente (48,1 % versus 63,8 %) y del injerto (63,3 % versus 74,7 %) en comparación con el grupo de trasplante renal con donantes con criterios estándar a los 10 años después del trasplante. La asociación de trasplante renal con donante de criterios expandidos y muerte o pérdida del injerto renal no fueron significativas cuando se ajustaron las variables en el modelo multivariado. Conclusión. El trasplante renal con donante de criterios expandidos tiene menor sobrevida del receptor y del injerto frente al grupo de trasplante renal con donante estándar. No hubo diferencias estadísticamente significativas en cuanto al trasplante renal con donante de criterios expandidos frente a la pérdida del injerto renal o muerte.

Introduction. Kidney transplantation is the treatment of choice for chronic kidney disease. Due to the gap with donor availability, the use of expanded criteria is an option that seeks to improve the global donation rate. The objective of this study was to compare the survival of the graft and the transplanted patient with an expanded criteria donor versus the standard donor. Methods. Retrospective cohort of 1002 kidney transplant patients where survival of the kidney graft and the recipient was determined at 10 years after transplantation. The survival of the kidney graft and the recipient were estimated by the Kaplan-Meier method. A Cox regression was performed by fitting the multivariate model. Results. The analysis included 1002 recipients with 18.8% (n=189) corresponding to the use of an expanded criteria donor. The expanded criteria donor kidney transplant group had lower patient (48.1% versus 63.8%) and graft (63.3% versus 74.7%) survival compared to the donor kidney transplant group with standard criteria at 10 years post-transplant. The association of kidney transplantation with expanded criteria donor and death or loss of the kidney graft were not significant when the variables were adjusted in the multivariate model. Conclusion. Kidney transplantation with an expanded criteria donor has a lower recipient and graft survival compared to the standard kidney transplant group. There were no statistically significant differences in expanded criteria donor kidney transplantation versus kidney graft loss or death.

Primeiros casos de rejeição em transplante penetrante após vacina contra COVID-19 / First cases of penetrating corneal transplant rejection after COVID-19 vaccines

RESUMO Este artigo descreve dois casos de reação imunológica de rejeição de transplante penetrante após a aplicação de dois tipos de vacina contra a COVID-19 - CoronaVac (Sinopharm/Butantan) e MRNA BNT162&2 (Pfizer-BioNTech) - com intervalo de 1 e 10 dias, respectivamente. A rejeição se manifestou com hiperemia, edema corneano e embaçamento da visão, que responderam rapidamente ao uso de corticoide tópico e subconjuntival. Até onde sabemos, este é o primeiro relato de rejeição de transplante penetrante de córnea pós-vacina anti-COVID-19. Recomendamos, presentemente, como prevenção, colírio de prednisolona a 1% 4 dias antes e durante 2 semanas após receber qualquer tipo de vacina para a COVID-19.

ABSTRACT This paper describes two cases of allograft corneal transplant rejection after the application of two types of COVID-19 vaccines - Coronavac (Sinopharm/Butantan) and MRNA BNT162&2 (Pfizer-BioNTech) vaccines - with an interval of 1 to 10 days, respectively. The rejection manifested in the form of corneal edema, hyperemia and blurred vision, which responded rapidly to the use of topical and subconjunctival corticosteroid. As far as we know, this is the first published report of immunological rejection of penetrating corneal transplant after COVID-19 vaccination. As a preventative measure, we now recommend the use of 1% prednisolone eye drop 4 days before and during 2 weeks after having received any type of COVID-19 vaccine.

The dual mTORC1/2 inhibitor AZD2014 inhibits acute graft rejection in a rat liver transplantation model / 南方医科大学学报

OBJECTIVE@#To investigate the inhibitory effect of AZD2014, a dual mTORC1/2 inhibitor, against acute graft rejection in a rat model of allogeneic liver transplantation.@*METHODS@#Liver transplantation from Lewis rat to recipient BN rat (a donor-recipient combination that was prone to induce acute graft rejection) was performed using Kamada's two-cuff technique. The recipient BN rats were randomized into 2 groups for treatment with daily intraperitoneal injection of AZD2014 (5 mg/kg, n=4) or vehicle (2.5 mL/kg, n=4) for 14 consecutive days, starting from the first day after the transplantation. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBIL) levels of the rats were measured 3 days before and at 1, 3, 5, 7, 10, and 14 days after the transplantation, and the survival time of the rats within 14 days were recorded. Immunohistochemical staining was used to examine the expressions of CD3 and Foxp3 in the liver graft, and acute graft rejection was assessed using HE staining based on the Banff schema.@*RESULTS@#Three rats in the control group died within 14 days after the surgery, while no death occurred in the AZD2014 group, demonstrating a significantly longer survival time of the rats in AZD2014 group (χ2=4.213, P=0.04). Serum ALT, AST and TBIL levels in the control group increased progressively after the surgery and were all significantly higher than those in AZD2014 group at the same time point (P < 0.05). Pathological examination revealed significantly worse liver graft rejection in the control group than in AZD2014 group based on assessment of the rejection index (P < 0.01); the rats in the control group showed more serious T lymphocyte infiltration and significantly fewer Treg cells in the liver graft than those in AZD2014 group (P < 0.01).@*CONCLUSIONS@#AZD2014 can effectively inhibit acute graft rejection in rats with allogeneic liver transplantation.

Retrasplante cardíaco: reporte de un caso / Cardiac re-transplantation: case report

RESUMEN: El Trasplante cardíaco es la mejor alternativa para la insuficiencia cardíaca terminal, logrando buenos resultados de sobrevida y calidad de vida a largo plazo. Una de las causas más importantes de morbimortalidad es la falla del injerto, la que puede ser secundaria, entre otros, a rechazo agudo y/o vasculopatía y su presencia requiere considerar todas las alternativas terapéuticas, dentro de las cuales está el retrasplante. Los resultados de sobrevida en retrasplante cardíaco son buenos. No obstante, los pacientes presentan los riesgos de una terapia inmunosupresora más intensa, así como el desarrollo recurrente de vasculopatía del injerto. Por lo que se considera una opción en pacientes cuidadosamente seleccionados, dado que la experiencia internacional demuestra que la sobrevida del retrasplante es menor que en el primer trasplante. Presentamos el caso de un paciente trasplantado a los 42 años, quien desarrolla una enfermedad vascular del injerto e insuficiencia cardíaca con capacidad funcional IV, por lo cual se decidió realizar un retrasplante cardíaco.

ABSTRACT: Cardiac transplantation is the best alternative for terminal heart failure, achieving good long-term survival and life quality. One of the most important causes of morbidity and mortality is graft failure, which may be secondary, among others, to acute rejection and / or vasculopathy and its presence requires the consideration of all therapeutic alternatives, re transplantation being one of them. The results of survival in cardiac retransplantation are good; however, they present the risks of a more intense immunosuppressive therapy as well as the recurrent development of graft vasculopathy. Therefore, it is considered an option in carefully selected patients given that international experience shows that the survival of retransplantation is lower than in primary cases. We present the case of a 42 year old transplanted patient , who developed graft vascular disease with progressive deterioration of his ventricular function leading to functional class IV. for which a cardiaccardiac retransplantation was performed.

C-Reactive protein level and left ventricular mass are associated with acute cellular rejection after heart transplant

OBJECTIVES: Acute cellular rejection (ACR) remains a major complication of heart transplant (HT). The gold standard for its diagnosis is endomyocardial biopsy (EMB), whereas the role of non-invasive biomarkers for detecting ACR is unclear. This study aimed to identify non-invasive biomarkers for the diagnosis of ACR in patients undergoing HT and presenting with normal left ventricular function. METHODS: We evaluated patients who underwent HT at a single center between January 2010 and June 2019. Patients were enrolled after HT, and those with left ventricular (LV) systolic dysfunction before EMB were excluded. We included only the results of the first EMB performed at least 30 days after HT (median, 90 days). Troponin, B-type natriuretic peptide (BNP), and C-reactive protein (CRP) levels were measured and echocardiography was performed up to 7 days before EMB. ACR was defined as International Society for Heart and Lung Transplantation grade 2R or 3R on EMB. We performed logistic regression analysis to identify the non-invasive predictors of ACR (2R or 3R) and evaluated the accuracy of each using area under the receiver operator characteristic curve analysis. RESULTS: We analyzed 72 patients after HT (51.31±13.63 years; 25 [34.7%] women); of them, 9 (12.5%) developed ACR. Based on multivariate logistic regression analysis, we performed forward stepwise selection (entry criteria, p<0.05). The only independent predictors that remained in the model were CRP level and LV mass index. The optimal cut-off point for CRP level was ≥15.9 mg/L (odds ratio [OR], 11.7; p=0.007) and that for LV mass index was ≥111 g/m2 (OR, 13.6; p=0.003). The area under the receiver operating characteristic curve derived from this model was 0.87 (95% confidence interval [CI], 0.75-0.99), with sensitivity of 85.7% (95% CI, 42.1%-99.6%), specificity of 78.4% (95% CI, 64.7%-88.7%), positive predictive value of 35.3% (95% CI, 14.3%-61.7%), and negative predictive value of 97.6% (95% CI, 87.1%-99.9%). CONCLUSIONS: Among patients undergoing HT, CRP level and LV mass were directly associated with ACR, but troponin and BNP levels were not.

An open-label randomized clinical trial to evaluate the efficacy of everolimus versus tacrolimus in triple maintenance immunosuppressive therapy for kidney transplant patients

Tacrolimus (TAC), a calcineurin inhibitor, and everolimus (EVL), an mTOR inhibitor, have been used as immunosuppressive (ISS) drugs in post-kidney transplantation therapy. The objective of this study was to compare the efficacy of EVL vs TAC in the ISS maintenance triple therapy. Ninety-seven kidney transplant patients, who received triple maintenance therapy with TAC, mycophenolate mofetil (MMF), and methyl prednisone (PRED), were evaluated. After four months of post-kidney transplant therapy, 30 patients enrolled in a randomized controlled clinical trial, in which 16 patients received TAC+MMF+PRED (cohort 1), and 14 patients switched to EVL+MMF+PRED (cohort 2). The patients were followed-up for 36 months. Two patients from cohort 1 lost their grafts after one year due to non-adherence. Two patients from cohort 2 had intolerance to mTOR inhibitors and were switched back to TAC from EVL. One case (6.25%) in cohort 1 and three cases (21.43%) in cohort 2 of acute T-cell-mediated rejection was observed. Antibody-mediated acute rejection (ABMAR) was observed in four patients (25.0%) in cohort 1, and antibody-mediated chronic rejection (ABMCR) was observed in two patients (12.50%). One patient from cohort 2 lost the graft after 15 months due to polyomavirus infection. The graft survival rate was 87.50% in cohort 1 and 92.86% in cohort 2. This clinical trial showed that the EVL+MMF+PRED triple maintenance therapy was efficacious compared with TAC during 32 months of follow-up. However, further studies are needed to confirm the efficacy of this regimen for long-term graft survival.

Safety and effectiveness of mycophenolate mofetil associated with tacrolimus for liver transplantation immunosuppression: a systematic review and meta-analysis of randomized controlled trials

A combination of immunosuppressants may improve outcomes due to the synergistic effect of their different action mechanisms. Currently, there is no consensus regarding the best immunosuppressive protocol after liver transplantation. This review aimed to evaluate the effectiveness and safety of tacrolimus associated with mycophenolate mofetil (MMF) in patients undergoing liver transplantation. We performed a systematic review and meta-analysis of randomized clinical trials. Eight randomized trials were included. The proportion of patients with at least one adverse event related to the immunosuppression scheme with tacrolimus associated with MMF was 39.9%. The tacrolimus with MMF immunosuppression regimen was superior in preventing acute cellular rejection compared with that of tacrolimus alone (risk difference [RD]=-0.11; p =0.001). The tacrolimus plus MMF regimen showed no difference in the risk of adverse events compared to that of tacrolimus alone (RD=0.7; p=0.66) and cyclosporine plus MMF (RD=-0.7; p=0.37). Patients undergoing liver transplantation who received tacrolimus plus MMF had similar adverse events when compared to patients receiving other evaluated immunosuppressive regimens and had a lower risk of acute rejection than those receiving in the monodrug tacrolimus regimen.

Early stage of antibody-mediated rejection after lung transplantation： A case report and literature review / 中南大学学报(医学版)

Antibody-mediated rejection (AMR) is a rare and serious complication after lung transplantation, with no characteristic of pathological manifestation, no systematic standard treatment, and the poor efficacy and prognosis. We reported a case of early AMR after lung transplantation and the relevant literature has been reviewed. A male patient presented with symptoms of cold 99 days after transplantation and resolved after symptomatic treatment. He admitted to the hospital 14 days later because of a sudden dyspnea and fever. Anti-bacteria, anti-fungi, anti-virus, and anti-pneumocystis carinii treatment were ineffective, and a dose of 1 000 mg methylprednisolone did not work too. The patient's condition deteriorated rapidly and tracheal intubation was done to maintain breathing. Serum panel reactive antibody and donor specific antibody showed postive in humen leukocyte antigen (HLA) II antibody. Pathological examination after transbronchial transplantation lung biopsy showed acute rejection. Clinical AMR was diagnosed combined the donor-specific antibody with the pathological result. The patient was functionally recovered after combined treatment with thymoglobuline, rituximab, plasmapheresis, and immunoglobulin. No chronic lung allograft dysfunction was found after 3 years follow up. We should alert the occurrence of AMR in lung transplantation recipient who admitted to hospital with a sudden dyspnea and fever while showed no effect after common anti-infection and anti-rejection treatment. Transbronchial transplantation lung biopsy and the presence of serum donor-specific antibody are helpful to the diagnosis. The treatment should be preemptive and a comprehensive approach should be adopted.

Donor-specific antibodies, glomerulitis, and human leukocyte antigen B eplet mismatch are risk factors for peritubular capillary C4d deposition in renal allografts / 中华医学杂志(英文版)

BACKGROUND@#The complement system plays an important role in the immune response to transplantation, and the diagnostic significance of peritubular capillary (PTC) C4d deposition (C4d+) in grafts is controversial. The study aimed to fully investigate the risk factors for PTC C4d+ and analyze its significance in biopsy pathology of kidney transplantation.@*METHODS@#This retrospective study included 124 cases of kidney transplant with graft biopsy and donor-specific antibody (DSA) testing from January 2017 to December 2019 in a single center. The effects of recipient pathological indicators, eplet mismatch (MM), and DSAs on PTC C4d+ were examined using univariate and multivariate logistic regression analyses.@*RESULTS@#In total, 35/124 (28%) were PTC C4d+, including 21 with antibody-mediated rejection (AMR), eight with renal tubular injury, three with T cell-mediated rejection, one with glomerular disease, and two others. Univariate analysis revealed that DSAs (P < 0.001), glomerulitis (P < 0.001), peritubular capillaritis (P < 0.001), and human leukocyte antigen (HLA) B eplet MM (P = 0.010) were the influencing factors of PTC C4d+. According to multivariate analysis, DSAs (odds ratio [OR]: 9.608, 95% confidence interval [CI]: 2.742-33.668, P < 0.001), glomerulitis (OR: 3.581, 95%CI: 1.246-10.289, P = 0.018), and HLA B eplet MM (OR: 1.166, 95%CI: 1.005-1.353, P = 0.042) were the independent risk factors for PTC C4d+. In receiver operating characteristic curve analysis, the area under the curve was increased to 0.831 for predicting PTC C4d+ when considering glomerulitis, DSAs, and HLA B eplet MM. The proportions of HLA I DSAs and PTC C4d+ in active antibody-mediated rejection were 12/17 and 15/17, respectively; the proportions of HLA class II DSAs and PTC C4d+ in chronic AMR were 8/12 and 7/12, respectively. Furthermore, the higher the PTC C4d+ score was, the more serious the urinary occult blood and proteinuria of recipients at the time of biopsy.@*CONCLUSIONS@#PTC C4d+ was mainly observed in AMR cases. DSAs, glomerulitis, and HLA B eplet MM are the independent risk factors for PTC C4d+.