Kidney transplant in the next decade: Strategies, challenges and vision of the future.

Although the results of kidney transplantation (KT) have improved substantially in recent years, a chronic and inexorable loss of grafts mainly due to the death of the patient and chronic dysfunction of the KT, continues to be observed. The objectives, thus, to optimize this situation in the next decade are fundamentally focused on minimizing the rate of kidney graft loss, improving patient survival, increasing the rate of organ procurement and its distribution, promoting research and training in health professionals and the development of scientific registries providing clinical and reliable information that allow us to optimize our clinical practice in the field of KT. With this perspective, this review will deep into: (1) strategies to avoid chronic dysfunction and graft loss in the medium and long term; (2) to prolong patient survival; (3) strategies to increase the donation, maintenance and allocation of organs; (4) promote clinical and basic research and training activity in KT; and (5) the analysis of the results in KT by optimizing and merging scientific registries.

Evolution of kidney allograft loss causes over 40 years (1979-2019).

INTRODUCTION: The improvement of kidney allograft recipient and graft survival showed a decrease over the last 40 years. Long-term graft loss rate remained stable during a 25-year time span. Knowing the changing causes and the risk factors associated with graft loss requires special attention. The present study aimed to assess the causes of graft loss and kidney allograft recipient death. Also, we aimed to compare two different periods (1979-1999 and 2000-2019) to identify changes in the characteristics of the failed allografts and recipient and donors profile. METHODS AND PATIENTS: We performed a single-center cohort study. We included all the kidney transplant recipients at the Hospital del Mar (Barcelona) between May 1979 and December 2019. Graft loss was defined as recipient death with functioning graft and as loss of graft function (return to dialysis or retransplantation). We assessed the causes of graft loss using clinical and histological information. We also analyzed the results of the two different transplant periods (1979-1999 and 2000-2019). RESULTS: Between 1979 and 2019, 1522 transplants were performed. The median follow-up time was 56 (IQR 8-123) months. During follow-up, 722 (47.5%) grafts were lost: 483 (66.9%) due to graft failure and 239 (33.1%) due to death with functioning graft. The main causes of death were cardiovascular (25.1%), neoplasms (25.1%), and infectious diseases (21.8%). These causes were stable between the two periods of time. Only the unknown cause of death has decreased in the last period. The main cause of graft failure (loss of graft function) was the allograft chronic dysfunction (75%). When histologic information was available, antibody-mediated rejection (ABMR) and interstitial fibrosis/tubular atrophy (IF/TA) were the most frequent specific causes (15.9% and 12.6%). Of the graft failures, 213 (29.5%) were early (<1 year of transplantation). Vascular thrombosis was the main cause of early graft failure in the second period (2000-2019) (46.7%) and T-cell-mediated rejection (TCMR) was the main cause (31.3%) in the first period (1979-1999). The causes of late graft loss were similar between the two periods. CONCLUSIONS: The causes of kidney allograft recipient death are still due to cardiovascular and malignant diseases. Vascular thrombosis has emerged as a frequent cause of early graft loss in the most recent years. The evaluation of the causes of graft loss is necessary to improve kidney transplantation outcomes.

Trasplante renal en la próxima década: estrategias, retos y visión de futuro / Kidney transplant in the next decade: Strategies, challenges and vision of the future

Aunque los resultados del trasplante renal (TR) han mejorado sustancialmente en los últimos años, continúa observándose una pérdida crónica e inexorable de los injertos debido principalmente a la muerte del paciente y a la disfunción crónica del TR. Por tanto, los objetivos para optimizar esta situación en la próxima década se centran fundamentalmente en minimizar la tasa de pérdida de injertos renales, mejorar la supervivencia de los pacientes, incrementar la tasa de obtención de órganos y su distribución, fomentar la investigación y la formación de los profesionales sanitarios y la elaboración de registros científicos que proporcionen una información clínica y fiable que nos permita optimizar nuestra práctica clínica en el campo del TR. Con esta perspectiva, esta revisión profundizará en: 1) estrategias para evitar la disfunción crónica y la pérdida del injerto a medio y largo plazo; 2) prolongar la supervivencia del paciente; 3) estrategias para incrementar la donación, mantenimiento y distribución de órganos; 4) promocionar la investigación clínica y básica y la actividad formativa en TR; y 5) el análisis de los resultados en TR mediante la optimización y fusión de los registros. (AU)

Although the results of kidney transplantation (KT) have improved substantially in recent years, a chronic and inexorable loss of grafts mainly due to the death of the patient and chronic dysfunction of the KT, continues to be observed. The objectives, thus, to optimize this situation in the next decade are fundamentally focused on minimizing the rate of kidney graft loss, improving patient survival, increasing the rate of organ procurement and its distribution, promoting research and training in health professionals and the development of scientific registries providing clinical and reliable information that allow us to optimize our clinical practice in the field of KT. With this perspective, this review will deep into: (1) strategies to avoid chronic dysfunction and graft loss in the medium and long term; (2) to prolong patient survival; (3) strategies to increase the donation, maintenance and allocation of organs; (4) promote clinical and basic research and training activity in KT; and (5) the analysis of the results in KT by optimizing and merging scientific registries. (AU)

Evolución de las causas de pérdida del injerto en trasplante renal durante 40 años (1979-2019) / Evolution of kidney allograft loss causes over 40 years (1979-2019)

Introducción: La mejoría en la supervivencia del receptor y del injerto renal sufre un proceso de deceleración. La tasa de pérdida del injerto a medio y largo plazo permanece estable desde hace 25 años. Es fundamental conocer las causas de pérdida del injerto y los factores relacionados, así como identificar si se han producido cambios en las causas de pérdida del injerto en los últimos años. El objetivo del presente estudio fue evaluar las causas de pérdida del injerto según fallecimiento del receptor o pérdida del injerto con vuelta a diálisis/retrasplante, y analizar las causas específicas de pérdida del injerto en 2 épocas (1979-1999 y 2000-2019) para identificar cambios en el perfil de los injertos perdidos. Pacientes y métodos: Estudio retrospectivo de todos los trasplantes renales (TR) realizados en el Hospital del Mar (Barcelona) entre mayo-1979 y diciembre-2019. Consideramos pérdida del injerto el fallecimiento del paciente con injerto funcionante o el re-inicio de diálisis o retrasplante. Revisamos las causas de pérdida mediante información clínica e histológica, y analizamos los resultados en 2 periodos (1979-1999 y 2000-2019). (AU)

Introduction: The improvement of kidney allograft recipient and graft survival showed a decrease over the last 40 years. Long-term graft loss rate remained stable during a 25-year time span. Knowing the changing causes and the risk factors associated with graft loss requires special attention. The present study aimed to assess the causes of graft loss and kidney allograft recipient death. Also, we aimed to compare two different periods (1979-1999 and 2000-2019) to identify changes in the characteristics of the failed allografts and recipient and donors profile. Methods and patients: We performed a single-center cohort study. We included all the kidney transplant recipients at the Hospital del Mar (Barcelona) between May 1979 and December 2019. Graft loss was defined as recipient death with functioning graft and as loss of graft function (return to dialysis or retransplantation). We assessed the causes of graft loss using clinical and histological information. We also analyzed the results of the two different transplant periods (1979-1999 and 2000-2019). (AU)

Supervivencia del paciente trasplantado y del injerto renal en una cohorte retrospectiva en México / Transplant patient and kidney graft survival in a retrospective cohort in Mexico

Introducción: el conocimiento de la funcionalidad del injerto y la supervivencia del paciente es fundamental para valorar el éxito del trasplante renal. Objetivo: determinar la supervivencia de los pacientes trasplantados por tipo de donante y la funcionalidad de los injertos renales en una cohorte en México. Material y métodos: cohorte de trasplante renal de 2013 a 2017 en México. Se analizaron 790 pacientes seguidos por un año para valorar la supervivencia de los pacientes trasplantados por tipo de donante y la funcionalidad de los injertos renales. Para ello se usaron medidas de tendencia central y dispersión, así como tablas de supervivencia de Kaplan-Meier con SPSS, versión 25. Resultados: de los 790 pacientes, 518 fueron de donante vivo (65.56%) con supervivencia del paciente de 97.88% y de funcionalidad del injerto de 93.24% a 12 meses de seguimiento; 272 pacientes recibieron el injerto de donante fallecido con supervivencia del paciente de 91.18% y funcionalidad del injerto renal de 84.19%. Conclusiones: aún existe una diferencia de casi 5% en la supervivencia del paciente receptor de un donante vivo en referencia con un donante fallecido. Para la funcionalidad del injerto renal esta diferencia es > 7%. La donación cadavérica ha aumentado; sin embargo, incluso en cifras bajas es de aproximadamente el 35% en México

Background: Knowledge of the functionality of the graft and patient survival is essential to assess the success of kidney transplantation. Objective: To determine the survival of transplanted patients by type of donor and the functionality of kidney grafts in a cohort in Mexico. Material and methods: Kidney transplant cohort from 2013 to 2017 in Mexico. 790 patients followed up for one year were analyzed to assess the survival of transplanted patients by type of donor and the functionality of kidney grafts. For this, measures of central tendency and dispersion were used, as well as Kaplan-Meier survival tables with SPSS, version 25. Results: Out of the 790 patients, 518 were from living donors (65.56%) with patient survival of 97.88% and graft function of 93.24% at 12 months of follow-up; 272 patients received the graft from a deceased donor with patient survival of 91.18% and renal graft function of 84.19%. Conclusions: There is still a difference of almost 5% in the survival of the recipient patient from a living donor compared to a deceased donor. For the functionality of the kidney graft, this difference is > 7%. Cadaveric donation has increased; however, even at low figures is of approximately 35% in Mexico

Caracterización de la evolución clínica del trasplante renal en pacientes con virus de la hepatitis C positivo / Characterization of the clinical course of kidney transplantation in patients with positive hepatitis C virus

Introducción: La infección por el virus de la hepatitis C es un evento común en los receptores de trasplante renal que la arrastran desde su estancia en los tratamientos de hemodiálisis previos al implante. La positividad al virus C se ha asociado a una evolución desfavorable después del trasplante, dado por una mayor frecuencia de complicaciones clínicas, metabólicas e inmunológicas que repercuten de forma negativa tanto en la supervivencia del injerto como del paciente. Objetivos: Caracterizar la evolución clínica de los pacientes trasplantados de riñón con virus de la hepatitis C positivo y determinar la evolución de este grupo de enfermo de acuerdo a variables demográficas, clínicas y de supervivencia. Método: Estudio analítico, transversal, retrospectivo en pacientes trasplantados renales del Hospital Clínico Quirúrgico Hermanos Ameijeiras, desde el año 2005 al 2017. Se excluyeron los menores de 15 años, los retrasplantes, los trasplantes dobles y los combinados o cuando no se pudo obtener la información. Se comparan las variables escogidas entre enfermos que llegan al trasplante con serología positiva al virus C, (HVC positivos), con los HVC negativos. Resultados: Del total de 156 enfermos, 65 por ciento (102) fueron HVC positivos, no se encontraron diferencias entre grupo en cuanto a edad y sexo de receptores y donantes, así como tampoco en el tratamiento inmunosupresor utilizado. El donante vivo se empleó menos en los HVC positivos donde se encontraron más enfermos con poliquistosis renal. La necrosis tubular aguda (NTA) y el rechazo fueron más frecuentes en los HVC positivos, siendo la primera estadísticamente significativa, p=0,0421, también resultaron significativamente más frecuente en el grupo HVC positivo, la proteinuria, p=0,041, la elevación de enzimas hepáticas, p=0,047 y la diabetes postrasplante, p=0,047. La supervivencia del injerto y los pacientes fue menor en los HVC positivos. Conclusiones: En este estudio la hepatitis por virus C impacta negativamente en la evolución del injerto y propicia la aparición de algunas complicaciones clínicas, lo que sin dudas pudiera influir en una menor expectativa de vida tanto para el injerto como para el enfermo(AU)

Introduction: Hepatitis C virus infection is a common event in kidney transplant recipients that has dragged it along since their stay in hemodialysis treatments prior to implantation. Positivity to virus C has been associated with an unfavorable evolution after transplantation, due to higher frequency of clinical, metabolic and immunological complications that negatively affect both graft and patient survival. Objectives: To describe the clinical evolution of kidney transplant patients with positive hepatitis C virus and to determine the evolution of this group of patients according to demographic, clinical and survival variables. Method: An analytical, cross-sectional, retrospective study in kidney transplant patients at Hermanos Ameijeiras Hospital was carried out from 2005 to 2017. This study excluded children under 15 years of age, re-transplants, double and combined transplants or when it was not possible to gather the information. The variables chosen among patients who arrive at transplantation with positive serology for virus C (positive HCV) were compared with negative HCV. Results: One hundred and fifty six patients were the total, 65 percent (102) were HVC positive, no differences were found between groups in terms of age and sex of recipients and donors, nor in the immunosuppressive treatment used. The living donor was less used in positive HVC where more patients with polycystic kidney disease were found. Acute tubular necrosis (ATN) and rejection were more frequent in positive HVC, the former being statistically significant, p = 0.0421, proteinuria, p = 0.041, elevation was also significantly more frequent in the positive HVC group of liver enzymes, p = 0.047 and post-transplant diabetes, p = 0.047. Graft and patient survival was lower in positive HCV. Conclusions: In this study, hepatitis C virus has negative impact on the evolution of the graft and favors the appearance of some clinical complications, which undoubtedly could influence a shorter life expectancy for both the graft and the patient(AU)

Kidney transplant registries: How to optimise their utility? / Registros en trasplante renal: ¿cómo optimizar su utilidad?

The scientific Registries (RE) in renal transplantation (Tx) are very useful since they allow us to identify risk factors in this population and facilitate contrasting the information with other national and international registries, contributing to establishing strategies which improve outcomes in terms of survival. They constitute an organised and planned system that uses observational methods and standardised systematic processes, including adjusted risk models, to essentially evaluate survival outcomes. The scientific RE are complemented with clinical trials providing scientific evidence, but inexcusably need adequate statistical analysis to generate reliable clinical data that contribute to optimising the prognosis of the transplant population. In addition, scientific RE provide valuable information on the performance of Tx programmes and help generate prognostic indexes, which could contribute to improving survival. Under these prerequisites, this review will assess the following aspects related to the scientific RE in the Tx: 1) the concept and importance of implementing RE in Tx; 2) the measures that are needed for the correct execution of the scientific RE; 3) the benefits, quality and limitations of RE; 4) the statistical tools for the adequate analysis of survival; and 5) utility of RE in the evaluation of performance, quality and surveillance of transplant programmes and the generation of comorbidity índices.

Development and results of a novel pancreas transplant program in Spain: the surgeon's point of view. / Desarrollo y resultados de un nuevo programa de trasplante de páncreas en España: la visión del cirujano.

INTRODUCTION: Simultaneous kidney-pancreas transplantation for patients with type 1 diabetes and end-stage chronic renal disease is widely performed. However, the rate of surgical morbidity from pancreatic complications remains high. The aim of this study was to describe the development and results of a new program, from the point of view of the pancreatic surgeon. METHODS: We analyzed 53 simultaneous kidney-pancreas transplantations performed over a period of seven years (2009-2016), with a median follow up of 39 months (range: 1-86 months). RESULTS: Out of the total of this series, two patients died: one patient because of cardiac arrest immediately after surgery; and another patient due to traffic accident, complicated by pneumonia. Among the 51 living patients, two grafts were lost: one due to chronic rejection four years after transplantation; and the other due to arterial thrombosis 20 days after transplantation (the only case requiring transplantectomy). In ten patients, one or more re-operations were necessary due to the following: graft pancreatitis (n=4), small intestinal obstruction (n=4), arterial thrombosis (n=1), fistula (n=1) and hemoperitoneum (n=1). Overall patient and graft survival rates after 1, 3 and 5 years were 98, 95 and 95% and 96, 93 and 89%, respectively. CONCLUSIONS: This study has shown that the results of a new pancreas transplant program, which relies on the previous experience of other groups, do not demonstrate a learning curve. Adequate surgeon education and training, as well as the proper use of standardized techniques, should ensure optimal results.

Preemptive kidney transplantation in elderly recipients with kidneys discarded of very old donors: A good alternative.

BACKGROUND: The shortage of organs is a major hurdle in kidney transplantation, and one solution to the problem is to extend the age of the donor. However, organs from older donors are often discarded due to the macroscopic appearance of the parenchyma or major vessels. On the other hand, a large number of elderly patients are potential candidates for kidney transplantation, while many kidneys from elderly deceased donors are discarded due to a lack of age-matched recipients. In addition, a large number are often discarded due to the lack of compatible recipients among elderly patients undergoing chronic dialysis. A possible solution to avoid this wastage of kidneys potentially suitable for transplantation could be the performance of preemptive kidney transplantation (PKT) in carefully selected elderly patients. PKT improves graft and patient survival compared to other renal replacement therapy options. There is no information about PKT in elderly patients receiving kidneys from elderly deceased donors. METHODS: From 2007 to 2012, we performed a prospective observational study comparing 26 elderly patients receiving PKT with a control group of 26 elderly patients receiving a first transplant after prior dialysis. RESULTS: Mean age of recipients was 74.3±2.9 years and mean age of donors was 73.8±4.1 years. Induction immunosuppression was similar in both groups. Death-censored graft survival was 96% in the PKT group and 68% in the control group (p=0.02), at 5 years after transplantation. Immediate and delayed graft function occurred in 92% and 3.8%, respectively, of patients in the PKT group and 53% and 34.6% of patients in the control group (p=0.005). Acute rejection was significantly more frequent in PKT patients (23.1% vs 3.8%, p=0.043). At the end of follow-up time 35.5±20.1 months, the glomerular filtration rate was similar in both groups (42.2±11.7 vs 41.7±11.2ml/min, p-value=0.72). Patient survival was similar in the two groups. CONCLUSIONS: Elderly patients with end stage of renal disease non-dialysis may benefit from PKT elderly deceased donors whose kidneys were to be discarded for there are not patients in the waiting list.

Outcomes of liver transplant with donors over 70 years of age.

UNLABELLED: Organ shortage has forced transplant teams to progressively expand the acceptance of marginal donors. METHODS: We performed a comparative analysis of the post-transplant evolution depending on donor age (group I: less than 70 years old (n=474) vs. group II: 70 or more years old [n=105]) over a 10 year period (2002-2011). RESULTS: Donors over 70 years old were similar to donors less than 70 years old in terms of ICU stay, gender, weight, laboratory results, and use of vasoactive drugs. However, the younger donor group presented with cardiac arrest more often (GI: 14 vs. GII: 3%, P=.005). There were no differences in initial poor function (GI: 6% vs. GII: 7,7%; P=.71), ICU stay (GI: 2.7±2 vs. GII: 3.3±3.8, P=.46), hospital stay (GI: 13.5±10 vs. GII: 15.5±11, P=.1), or hospital mortality (GI: 5.3 vs. GII: 5.8%, P=.66) between receptors of more or less than 70 year old grafts. After a median follow up of 32 months, no differences were found in the incidence of biliary tract complications (GI: 17 vs. GII: 20%, P=.4) or vascular complications (GI: 11 vs. GII: 9%, P=.69). The actuarial 5 year survival was similar for both study groups (GI: 70 vs. GII: 76%, P=.54). CONCLUSIONS: In our experience, the use of grafts from donors older than 70 years, when other risk factors are avoided (cold ischemia, steatosis, sodium levels), does not worsen the results of liver transplantation on the short or long term.