LIGHT/HVEM/LTßR interaction as a target for the modulation of the allogeneic immune response in transplantation.

The exchange of information during interactions of T cells with dendritic cells, B cells or other T cells regulates the course of T, B and DC-cell activation and their differentiation into effector cells. The tumor necrosis factor superfamily member LIGHT (homologous to lymphotoxin, exhibits inducible expression and competes with HSV glycoprotein D for binding to herpesvirus entry mediator, a receptor expressed on T lymphocytes) is transiently expressed upon T cell activation and modulates CD8 T cell-mediated alloreactive responses upon herpes virus entry mediator (HVEM) and lymphotoxin ß receptor (LTßR) engagement. LIGHT-deficient mice, or WT mice treated with LIGHT-targeting decoy receptors HVEM-Ig, LTßR-Ig or sDcR3-Ig, exhibit prolonged graft survival compared to untreated controls, suggesting that LIGHT modulates the course and severity of graft rejection. Therefore, targeting the interaction of LIGHT with HVEM and/or LTßR using recombinant soluble decoy receptors or monoclonal antibodies represent an innovative therapeutic strategy for the prevention and treatment of allograft rejection and for the promotion of donor-specific tolerance.

Benchmarking in the process of donation after brain death: a methodology to identify best performer hospitals.

A benchmarking approach was developed in Spain to identify and spread critical success factors in the process of donation after brain death. This paper describes the methodology to identify the best performer hospitals in the period 2003-2007 with 106 hospitals throughout the country participating in the project. The process of donation after brain death was structured into three phases: referral of possible donors after brain death (DBD) to critical care units (CCUs) from outside units, management of possible DBDs within the CCUs and obtaining consent for organ donation. Indicators to assess performance in each phase were constructed and the factors influencing these indicators were studied to ensure that comparable groups of hospitals could be established. Availability of neurosurgery and CCU resources had a positive impact on the referral of possible DBDs to CCUs and those hospitals with fewer annual potential DBDs more frequently achieved 100% consent rates. Hospitals were grouped into each subprocess according to influencing factors. Hospitals with the best results were identified for each phase and hospital group. The subsequent study of their practices will lead to the identification of critical factors for success, which implemented in an adapted way should fortunately lead to increasing organ availability.

Continuously evaluating performance in deceased donation: the Spanish quality assurance program.

The Spanish Quality Assurance Program applied to the process of donation after brain death entails an internal stage consisting of a continuous clinical chart review of deaths in critical care units (CCUs) performed by transplant coordinators and periodical external audits to selected centers. This paper describes the methodology and provides the most relevant results of this program, with information analyzed from 206,345 CCU deaths. According to the internal audit, 2.3% of hospital deaths and 12.4% of CCU deaths in Spain yield potential donors (clinical criteria consistent with brain death). Out of the potential donors, 54.6% become actual donors, 26% are lost due to medical unsuitability, 13.3% due to refusals to donation, 3.1% due to maintenance problems and 3% due to other reasons. Although the national pool of potential donors after brain death has progressively decreased from 65.2 per million population (pmp) in 2001 to 49 pmp in 2010, the number of actual donors after brain death has remained at about 30 pmp. External audits reveal that the number of actual donors could be 21.6% higher if all potential donors were identified and preventable losses avoided. We encourage other countries to develop similar comprehensive approaches to deceased donation performance.

Characteristics of patients registered with chronic renal disease in Castilla y León and survival analysis of transplanted patients and their grafts.

INTRODUCTION: Chronic kidney disease (CKD) is an important public health problem. Kidney transplantation is associated with increase survival and improvement of quality of life. OBJECTIVES: To describe the sociodemographic and clinical characteristics of patients registered in Castilla y León. To perform a survival analysis of transplant patients and their grafts. To evaluate survival depending on the transplant centre. METHODS: Descriptive study with data collected until 31 December 2008 from the Registro de Diálisis y Trasplante Renal de la Comunidad de Castilla y León (REDI). The data was described differentiating prevalent and incidents patients. Survival data was assessed with the Kaplan-Meier method. RESULTS: On 31 December 2008, 2.498 patients were on Renal Replacement Therapy (RRT) (976.8 pmp); in 2008, 337 started treatment (131.8 pmp) and 94 received kidney transplant (36.8 pmp). The first cause of CKD for incident patients is diabetes (25.0%), followed by vascular diseases (18.1%). For prevalent patients: glomerulonephritis (16.5%) and diabetes (14.4%). Differences (p = 0.0021) were observed for the treatment initiation age, group of disease and prevalent patients (p <0.0001). During 11 years 1.062 transplants were performed in 1.012 patients and 879 are still functioning (83%). In this period, the survival probability for the transplant patients is 81.076% (± 0.023), and for the 838 patients with first functioning graft is 89.336% (± 0.016). Median graft survival is between 8.7 and 9.3 years (95% confidence). CONCLUSIONS: Most of the transplants during the last 11 years are still functioning. There are no differences when comparing graft survival at the approved centers in Castilla y León (p = 0.358).

Características de los pacientes registrados con enfermedad renal crónica en Castilla y León y análisis de supervivencia de los trasplantados y de sus injertos / Characteristics of patients registered with chronic renal disease in Castilla y León and survival analysis of transplanted patients and their grafts

Introducción: La enfermedad renal crónica (ERC) es un problema importante de salud pública. El trasplante renal se relaciona con el aumento de la supervivencia y con la mejora en la calidad de vida. Objetivos: Describir las características sociodemográficas y clínicas de los pacientes registrados en Castilla y León. Realizar un análisis de supervivencia de los pacientes sometidos a trasplante y de sus injertos. Evaluar la supervivencia en función del centro de trasplante. Métodos: Estudio descriptivo con datos recogidos hasta 31 de diciembre de 2008 en el Registro de Diálisis y Trasplante Renal de la Comunidad de Castilla y León (REDI). Descripción general de los pacientes, diferenciando incidentes de prevalentes. Se realizaron análisis de supervivencia utilizando el método de Kaplan-Meier. Resultados: A 31 de diciembre de 2008, había 2.498 pacientes en tratamiento sustitutivo renal (TSR) (976,8 pacientes por millón de población, pmp); en 2008, 337 iniciaron tratamiento (131,8 pmp) y 94 fueron sometidos a trasplante (36,8 pmp). La causa más frecuente de ERC en pacientes incidentes es la diabetes (25,0%), seguida de las enfermedades vasculares (18,1%). En pacientes prevalentes las causas más frecuentes son glomerulonefritis (16,5%) y diabetes (14,4%). Hay diferencias (p = 0,0021) en la edad de inicio del tratamiento, según grupo de enfermedad (en prevalentes también, p <0,0001) (AU)

Introduction: Chronic kidney disease (CKD) is an important public health problem. Kidney transplantation is associated with increase survival and improvement of quality of life. Objectives: To describe the sociodemographic and clinical characteristics of patients registered in Castilla y León. To perform a survival analysis of transplant patients and their grafts. To evaluate survival depending on the transplant centre. Methods: Descriptive study with data collected until 31 December 2008 from the Registro de Diálisis y Trasplante Renal de la Comunidad de Castilla y León (REDI). The data was described differentiating prevalent and incidents patients. Survival data was assessed with the Kaplan-Meier method. Results: On 31 December 2008, 2.498 patients were on Renal Replacement Therapy (RRT) (976.8 pmp); in 2008, 337 started treatment (131.8 pmp) and 94 received kidney transplant (36.8 pmp) (AU)

[Dialysis and transplant. Spain in 2005]. / Informe de Situación de Diálisis y Trasplante en España, 2005.

In 2005, renal replace treatment (dialysis and transplant) was necessary for about 40,000 people, without being known the number accurate and either their basic characteristics, such as: time in treatment, modality or treatment changes. The presented data cover the 76% of the Spanish population and are the result of the cooperation among technicians of registries, nephrologists and transplant coordinations. 4,125 people started RRT in 2005, the total estimated acceptance rate for renal replacement therapy in adults in Spain was 126 pmp and regarding other European countries it locates us in an intermediate area. The incidence rate seems to keep stable in the last years although there were some differences among communities (from 104 pmp in Castile and Leon to 186 pmp in Canary Islands). Diabetes Mellitus is the most diagnosed cause of renal failure in 2005, more than 20% of patients, followed by vascular diseases. The estimated prevalence of renal replacement therapy in Spain at the end of 2005 was 903 pmp, with important variations among communities (from 806 pmp in Cantabria to 1056 pmp in Valencia Region). The 47% of prevalent RRT patients had a functioning transplant. Mortality on haemodialysis and peritoneal dialysis was 13.7% and 10.8% respectively. Mortality on transplant was 1.3%, one of the lowest values registered so far. Mortality on renal replacement therapy was around 5% among patients from 45 to 64 years, 11% between 65 and 74 years and 19% among the patients older than 75 years.

Informe de situación de diálisis y trasplante en España, 2004 / Dialysis and transplant situation, Spain 2004

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