Validación de marcadores de pronóstico en la evolución inicial de trasplante renal

[ES] El trasplante de órganos, y en especial el Trasplante Renal (TR), ha supuesto un gran avance en los últimos 50 años, siendo quizá uno de los mayores ¨hitos¨ del siglo XX. Desde que se realizó el primer TR en Boston, (EE.UU.), entre dos gemelos idénticos en el año 1954 ha mejorado mucho la técnica quirúrgica, el tratamiento médico posterior a la cirugía, se han desarrollado mejores fármacos inmunosupresores, y ha disminuido la incidencia de infecciones entre estos enfermos. El TR es el tratamiento de elección para todos aquellos que sufren Enfermedad Renal Crónica (ERC), y su condición física lo permite, ya que aumenta la supervivencia cuando se compara con aquellos que permanecen en lista de espera y más aún con respecto a los que reciben tratamiento renal sustitutivo (TRS) con hemodiálisis o diálisis peritoneal . Según datos de la Organización Nacional de Trasplante (ONT), España es líder mundial en donación y trasplante de órganos. En el año 2014, se volvió a batir un record histórico, realizándose un total de 4.360 trasplantes de órganos sólidos, de los cuales 2.678 fueron trasplantes renales. También se ha evolucionado mucho en las diferentes categorías de TR, ya que si hasta el año 2003 prácticamente solo se realizaba trasplante de donante cadáver y el trasplante de donante vivo era testimonial, ahora ha aumentado esta modalidad, (trasplante de donante vivo), habiéndose realizado 423 en el año 2014, incluyendo trasplante cruzado (43 de los 423) y con donante en asistolia tipo II y tipo III de Maastricht, con 191 donantes el año pasado. Esto hace que aumenten las variables que hay que controlar, para obtener una mejor supervivencia, tanto del injerto como de los pacientes trasplantados. Uno de los puntos importantes para poder lograr una mayor supervivencia, es ofrecer a cada paciente el tratamiento inmunosupresor más adecuado según sus características. Existen varios agentes Introducción 3 terapéuticos que pueden ayudar a lograr este objetivo. El primer intento de inmunosupresión fue la irradiación total del organismo. Posteriormente, aparecieron fármacos como la Azatioprina, desde los años 60 que se usaba asociada a Corticoides. La incidencia de Rechazo Agudo (RA) con esta combinación era del 80%. Desde la mitad de los años 70 se pudo disponer de los anticuerpos policlonales antitimocíticos (ATG) y globulina antilinfocítica (ALG), que se utilizaron para el tratamiento del rechazo corticorresistente utilizando como protocolo de base Azatioprina y Corticoides. Los resultados de los primeros años mostraron una supervivencia del injerto del 50% y una mortalidad, principalmente de causa infecciosa, del 10-20%. El cambio fundamental en los resultados del TR en los años 80 fue debido a la introducción de la Ciclosporina (CsA) como inmunosupresor básico asociado a Corticoides. La tasa de RA disminuyó hasta el 40-50% y la supervivencia del injerto al año aumentó al 80% con una mortalidad más baja, debido a la disminución de la dosis de Corticoides y a los avances quirúrgicos y médicos mencionados. El tratamiento habitual consistía en doble terapia: Corticoides a dosis bajas, y CsA, y en ocasiones se usaba una triple terapia con Azatioprina como agente coadyuvante. El principal problema de la CsA es su efecto nefrotóxico, tanto agudo y reversible, como crónico, con gran influencia en la supervivencia del injerto a largo plazo. En el año 1985 estuvo disponible el primer anticuerpo monoclonal utilizado en la práctica clínica: el OKT3. Se utilizó como tratamiento del RA corticorresistente con gran eficacia, pero con importantes efectos secundarios, como el síndrome de la primera dosis por liberación de citoquinas. Algunos grupos lo utilizaron como tratamiento de inducción

Factors affecting diabetic patient’s long-term quality of life after simultaneous pancreas-kidney transplantation: a single-center analysis

[Purpose]: Pancreas transplantation (PT) is one of the few ways to restore euglycemia within diabetic patients; however, the high morbidity caused by surgical complications and the need for immunosuppressive therapy has raised controversy about PT improving the health-related quality-of-life (HRQoL). The aim of this study is to assess the long-term (≥ 5 years after PT) HRQoL and to identify the factors affecting it.[Methods]: A single-center, cross-sectional study of 49 sequential PT was performed. All patients conducted a telephone interview to fulfill the modification of Medical Outcome Health Survey Short Form questionnaire (SF-36v2) and were compared to similar post-PT studies from the literature.[Results]: Patients with a history of replacement renal therapy (RRT) or neuropathy undergoing a PT were associated to a worse bodily pain (P = 0.03) and physical function (P = 0.04), respectively, whereas those with retinopathy showed an improved Role Emotional (P = 0.04). Multivariate analysis revealed the presence of RRT as the only independent prognostic factor for a worse bodily pain [relative risk = 3.9; 95% confidence interval (1.1–14.6)], (P = 0.04). Furthermore, nearly all PT recipients (91.8%) claimed an overall better health than prior to PT.[Conclusion]: Our study confirms that PT recipients’ HRQoL improves after PT, showing similar HRQoL scores across different populations and suggests that patients in predialysis could benefit from an improved HRQoL if transplanted on the early stages of the disease

Manejo de la inmunosupresión en pacientes trasplantados de riñón con COVID19. Estudio multicéntrico nacional derivado del registro COVID de la Sociedad Española de Nefrología

Introduction: SARS CoV2 infection has had a major impact on renal transplant patients with a high mortality in the first months of the pandemic. Intentional reduction of immunosuppressive therapy has been postulated as one of the cornerstone in the management of the infection in the absence of targeted antiviral treatment. This has been modified according to the patient`s clinical situation and its effect on renal function or anti-HLA antibodies in the medium term has not been evaluated.Objectives: Evaluate the management of immunosuppressive therapy made during SARS-CoV2 infection, as well as renal function and anti-HLA antibodies in kidney transplant patients 6 months after COVID19 diagnosis.Material and methods: Retrospective, national multicentre, retrospective study (30 centres) of kidney transplant recipients with COVID19 from 01/02/20 to 31/12/20. Clinical variables were collected from medical records and included in an anonymised database. SPSS statistical software was used for data analysis.Results: renal transplant recipients with COVID19 were included (62.6% male), with a mean age of 57.5 years. The predominant immunosuppressive treatment prior to COVID19 was triple therapy with prednisone, tacrolimus and mycophenolic acid (54.6%) followed by m-TOR inhibitor regimens (18.6%). After diagnosis of infection, mycophenolic acid was discontinued in 73.8% of patients, m-TOR inhibitor in 41.4%, tacrolimus in 10.5% and cyclosporin A in 10%. In turn, 26.9% received dexamethasone and 50.9% were started on or had their baseline prednisone dose increased. Mean creatinine before diagnosis of COVID19, at diagnosis and at 6 months was: 1.7 +/- 0.8, 2.1 +/- 1.2 and 1.8 +/- 1 mg/dl respectively (p < 0.001). 56.9% of the patients (N = 350) were monitored for anti-HLA antibodies. 94% (N = 329) had no anti-HLA changes, while 6% (N = 21) had positive anti-HLA antibodies. Among the patients with donor-specific antibodies post-COVID19 (N = 9), 7 patients (3.1%) had one immunosuppressant discontinued (5 patients had mycophenolic acid and 2 had tacrolimus), 1 patient had both immunosuppressants discontinued (3.4%) and 1 patient had no change in immunosuppression (1.1%), these differences were not significant.Conclusions: The management of immunosuppressive therapy after diagnosis of COVID19 was primarily based on discontinuation of mycophenolic acid with very discrete reductions or discontinuations of calcineurin inhibitors. This immunosuppression management did not influence renal function or changes in anti-HLA antibodies 6 months after diagnosis

Use of tocilizumab in kidney transplant recipients with COVID-1

Acute respiratory distress syndrome associated with coronavirus infection is related to a cytokine storm with large interleukin-6 (IL-6) release. The IL-6-receptor blocker tocilizumab may control the aberrant host immune response in patients with coronavirus disease 2019 (COVID-19) . In this pandemic, kidney transplant (KT) recipients are a high-risk population for severe infection and showed poor outcomes. We present a multicenter cohort study of 80 KT patients with severe COVID-19 treated with tocilizumab during hospital admission. High mortality rate was identified (32.5%), related with older age (hazard ratio [HR] 3.12 for those older than 60 years, P = .039). IL-6 and other inflammatory markers, including lactic acid dehydrogenase, ferritin, and D-dimer increased early after tocilizumab administration and their values were higher in nonsurvivors. Instead, C-reactive protein (CRP) levels decreased after tocilizumab, and this decrease positively correlated with survival (mean 12.3 mg/L in survivors vs. 33 mg/L in nonsurvivors). Each mg/L of CRP soon after tocilizumab increased the risk of death by 1% (HR 1.01 [confidence interval 1.004-1.024], P = .003). Although patients who died presented with worse respiratory situation at admission, this was not significantly different at tocilizumab administration and did not have an impact on outcome in the multivariate analysis. Tocilizumab may be effective in controlling cytokine storm in COVID-19 but randomized trials are needed

Patient and graft survival in pancreas transplant recipients: The EFISPAN study

Introduction and objectives: Graft outcomes in pancreas transplantation have improved in recent decades, but data are mainly derived from registries or prospective single-centre studies. This large epidemiological study was undertaken to investigate the impact of clinical and demographic factors on graft and patient survival in pancreas transplant recipients in Spain, and to provide robust, country-wide, practice-based data to complement registry findings. Patients and methods: We conducted a retrospective, longitudinal, epidemiological study to assess risk factors impacting patient and graft survival in pancreas transplant recipients in eight centres in Spain. All patients transplanted between 1 January 2008 and 31 December 2012 were included; data were collected until 31 December 2015. The Kaplan–Meier method was used for all time-to-event analyses, including patient survival, graft survival, acute rejection, and BPAR. For graft survival analysis, in cases of death with functioning graft, patients were censored without any event on the date of death. For acute rejection and BPAR, patients were censored without any event on the date of death or graft loss. Univariable and multivariable analyses (Cox proportional hazards model) were conducted to assess the association between baseline clinical and demographic characteristics and patient/graft survival. Results: Data were included for 241 (80.1%) simultaneous pancreas-kidney transplants, 56 (18.6%) pancreas-after-kidney transplants and 4 (1.3%) pancreas transplants alone. Mean ± standard deviation time from diagnosis until transplantation was 26.1 ± 7.5 years. Nineteen patients died, mainly due to infections (n = 10); the remaining 282 patients (93.7%) survived from transplantation until the end of the study. Among 55 patients (18.3%) with pancreas graft loss, the main reasons were vascular thrombosis (n = 19), chronic rejection (n = 10), acute rejection (n = 6) and death with a functioning graft (n = 5). The overall rate of vascular-related death was 1.3% at 5 years post transplant. Univariable analysis showed that patient age and weight, donor age, previous kidney transplantation, previous cardiovascular events and need for insulin more than 48 h post transplantation were significantly associated with pancreas graft survival. Of these, in multivariable analyses pancreas graft survival was inferior in patients who had received a previous kidney transplant prior to pancreas transplantation (log-rank test, p = 0.0002). Glucose metabolism, renal function and cardiovascular risk factors were generally stable following transplantation. Conclusions: The results of this multicentre study highlight the excellent patient and graft outcomes following pancreas transplantation, with a notably low incidence of cardiovascular events. Resumen: Introducción y objetivos: Los resultados del injerto en el trasplante de páncreas han mejorado en las últimas décadas, pero los datos provienen principalmente de registros o estudios prospectivos unicéntricos. Este estudio epidemiológico se llevó a cabo para investigar el impacto de los factores clínicos y demográficos en la supervivencia del injerto y del paciente en receptores de trasplante de páncreas en España, y proporcionar datos sólidos, basados en la práctica a nivel nacional, para complementar los hallazgos de los registros. Pacientes y métodos: Realizamos un estudio epidemiológico longitudinal, retrospectivo, para evaluar los factores de riesgo que influyen en la supervivencia del paciente y del injerto en receptores de trasplante de páncreas en 8 centros de España. Se incluyeron todos los pacientes trasplantados entre el 1 de enero de 2008 y el 31 de diciembre de 2012; los datos se recogieron hasta el 31 de diciembre de 2015. Se utilizó el método de Kaplan-Meier para todos los análisis del tiempo transcurrido hasta el evento, incluida la supervivencia del paciente, la supervivencia del injerto, el rechazo agudo y el BPAR. Para el análisis de la supervivencia del injerto, en los casos de muerte con injerto funcionante, los pacientes fueron censurados sin ningún evento en la fecha de la muerte. Para el rechazo agudo y BPAR, los pacientes fueron censurados sin ningún evento en la fecha de la muerte o pérdida del injerto. Se realizaron análisis univariables y multivariables (modelo de riesgos proporcionales de Cox) para evaluar la asociación entre las características clínicas y demográficas basales y la supervivencia del paciente/injerto. Resultados: Se incluyeron datos de 241 (80,1%) trasplantes de páncreas-riñón simultáneos, 56 (18,6%) trasplantes de páncreas después de riñón y 4 (1,3%) trasplantes de páncreas aislados. El tiempo medio ± desviación estándar desde el diagnóstico hasta el trasplante fue de 26,1 ± 7,5 años. Diecinueve pacientes fallecieron, principalmente por infecciones (n = 10); los 282 pacientes restantes (93,7%) sobrevivieron desde el trasplante hasta el final del estudio. De los 55 pacientes (18,3%) con pérdida del injerto de páncreas, las principales razones fueron trombosis vascular (n = 19), rechazo crónico (n = 10), rechazo agudo (n = 6) y muerte con un injerto funcionante (n = 5). La tasa global de muerte relacionada con eventos vasculares fue del 1,3% a los 5 años del trasplante. El análisis univariable mostró que la edad y el peso del paciente, la edad del donante, el trasplante renal previo, los eventos cardiovasculares previos y la necesidad de insulina durante más de 48 h después del trasplante se asociaron significativamente con la supervivencia del injerto de páncreas. De estos, en los análisis multivariables, la supervivencia del injerto de páncreas fue inferior en los pacientes que habían recibido un trasplante de riñón previo al trasplante de páncreas (prueba de rango logarítmico, p = 0,0002). El metabolismo de la glucosa, la función renal y los factores de riesgo cardiovasculares se mantuvieron en general estables después del trasplante. Conclusiones: Los datos obtenidos de este estudio multicéntrico destacan los excelentes resultados del paciente y del injerto después del trasplante de páncreas, con una incidencia notablemente baja de eventos cardiovasculares

Best practices during COVID-19 pandemic in solid organ transplant programs in Spain

Clinical management of transplant patients abruptly changed during the first months of COVID-19 pandemic (March to May 2020). The new situation led to very significant challenges, such as new forms of relationship between healthcare providers and patients and other professionals, design of protocols to prevent disease transmission and treatment of infected patients, management of waiting lists and of transplant programs during state/city lockdown, relevant reduction of medical training and educational activities, halt or delays of ongoing research, etc. The two main objectives of the current report are: 1) to promote a project of best practices in transplantation taking advantage of the knowledge and experience acquired by professionals during the evolving situation of the COVID-19 pandemic, both in performing their usual care activity, as well as in the adjustments taken to adapt to the clinical context, and 2) to create a document that collects these best practices, thus allowing the creation of a useful compendium for the exchange of knowledge between different Transplant Units. The scientific committee and expert panel finally standardized 30 best practices, including for the pretransplant period (n = 9), peritransplant period (n = 7), postransplant period (n = 8) and training and communication (n = 6). Many aspects of hospitals and units networking, telematic approaches, patient care, value-based medicine, hospitalization, and outpatient visit strategies, training for novelties and communication skills were covered. Massive vaccination has greatly improved the outcomes of the pandemic, with a decrease in severe cases requiring intensive care and a reduction in mortality. However, suboptimal responses to vaccines have been observed in transplant recipients, and health care strategic plans are necessary in these vulnerable populations. The best practices contained in this expert panel report may aid to their broader implementation.Funding: This Project was funded by an unrestricted grant from Chiesi Pharmaceuticals. Ampersand Consulting was also involved as a methodological adviso

Breakthrough Infections Following mRNA SARS-CoV-2 Vaccination in Kidney Transplant Recipients.

The clinical effectiveness of coronavirus disease 2019 (COVID-19) vaccination in kidney transplant (KT) recipients is lower than in the general population. From April to October 2021, 481 KT recipients with COVID-19, included in the Spanish Society of Nephrology COVID-19 Registry, were analyzed. Data regarding vaccination status and vaccine type were collected, and outcomes of unvaccinated or partially vaccinated patients (n = 130) were compared with fully vaccinated patients (n = 351). Clinical picture was similar and survival analysis showed no differences between groups: 21.7% of fully vaccinated patients and 20.8% of unvaccinated or partially vaccinated died (P = 0.776). In multivariable analysis, age and pneumonia were independent risk factors for death, whereas vaccination status was not related to mortality. These results remained similar when we excluded patients with partial vaccination, as well as when we analyzed exclusively hospitalized patients. Patients vaccinated with mRNA-1273 (n = 213) showed a significantly lower mortality than those who received the BNT162b2 vaccine (n = 121) (hazard ratio: 0.52; 95% confidence interval, 0.31-0.85; P = 0.010). COVID-19 severity in KT patients has remained high and has not improved despite receiving 2 doses of the mRNA vaccine. The mRNA-1273 vaccine shows higher clinical effectiveness than BNT162b2 in KT recipients with breakthrough infections. Confirmation of these data will require further research taking into account the new variants and the administration of successive vaccine doses

Recomendaciones para el trasplante renal de donante vivo

Esta guía de recomendaciones para el TR de donante vivo (TRDV) es un documento elaborado con el patrocinio de la Sociedad Española de Nefrología, la Sociedad Española de Trasplantes y la Organización Nacional de Trasplantes que actualiza la calidad de la evidencia disponible para ofrecer el mejor tratamiento de la insuficiencia renal crónica cuando se disponga de un donante vivo potencial. El objetivo principal de esta guía es proporcionar a los profesionales con responsabilidad en los estudios previos del donante vivo y del receptor trasplantado, las mejores herramientas para tomar decisiones en beneficio del donante vivo y del receptor del trasplante. Además, en el contexto actual del TR, el donante vivo debe recuperar el protagonismo que alcanzó en un pasado reciente. Para ello, las nuevas modalidades de donación HLA y/o ABO incompatible, así como la donación cruzada disponibles en diversos centros con experiencia en TRDV, son oportunidades adicionales para el tratamiento de enfermos renales que tienen un donante incompatible. Los buenos resultados en supervivencia del paciente y del injerto están ampliando las circunstancias de aceptación de donantes vivos de riñón, incluyendo donantes de mayor edad y otros con algunos condicionantes que incluyen antecedentes o alteraciones límite que, cuando son evaluados con criterios objetivos, pueden aportar un numero adicional de trasplantes. No se ha obviado en esta guía que el TRDV puede representar algún riesgo para el que dona. Estos problemas que pueden aparecer a corto o largo plazo tienen que ser objeto principal de valoración previa a la donación y presentados al potencial donante para que en ejercicio de su autonomía los asuma o rechace. La experiencia acumulada en los últimos años ha permitido avanzar en el análisis de riesgos para preservar la salud de los donantes, aspecto que debe estar siempre presente en los responsables de programas de TRDV cuando se procede al estudio de idoneidad de un potencial donante. Finalmente, esta guía ha sido estructurada para facilitar la toma de decisiones con recomendaciones y sugerencias ante incertidumbres derivadas de los resultados en los exhaustivos estudios predonación. Y todo ello, con el objetivo de que el consentimiento informado que debe certificar la calidad de los estudios y la información proporcionada a donante y receptor, alcancen las mayores garantías posibles

Recommendations for living donor kidney transplantation Recomendaciones para el trasplante renal de donante vivo

Altres ajuts: European Regional Development (Fund-ERDF).This Guide for Living Donor Kidney Transplantation (LDKT) has been prepared with the sponsorship of the Spanish Society of Nephrology (SEN), the Spanish Transplant Society (SET), and the Spanish National Transplant Organization (ONT). It updates evidence to offer the best chronic renal failure treatment when a potential living donor is available. The core aim of this Guide is to supply clinicians who evaluate living donors and transplant recipients with the best decision-making tools, to optimise their outcomes. Moreover, the role of living donors in the current KT context should recover the level of importance it had until recently. To this end the new forms of incompatible HLA and/or ABO donation, as well as the paired donation which is possible in several hospitals with experience in LDKT, offer additional ways to treat renal patients with an incompatible donor. Good results in terms of patient and graft survival have expanded the range of circumstances under which living renal donors are accepted. Older donors are now accepted, as are others with factors that affect the decision, such as a borderline clinical history or alterations, which when evaluated may lead to an additional number of transplantations. This Guide does not forget that LDKT may lead to risk for the donor. Pre-donation evaluation has to centre on the problems which may arise over the short or long-term, and these have to be described to the potential donor so that they are able take them into account. Experience over recent years has led to progress in risk analysis, to protect donors' health. This aspect always has to be taken into account by LDKT programmes when evaluating potential donors. Finally, this Guide has been designed to aid decision-making, with recommendations and suggestions when uncertainties arise in pre-donation studies. Its overarching aim is to ensure that informed consent is based on high quality studies and information supplied to donors and recipients, offering the strongest possible guarantees