Antiphospholipase A2 receptor antibody-positive membranous nephropathy in the kidney donor: Lessons from a serendipitous transplantation.

Primary membranous nephropathy (PMN) is an autoimmune disease limited to the kidney that is characterized by the presence of circulating PLAR2 antibodies in 70% of the cases and usually positivity for PLA2R and IgG4 by immunohistochemistry (IHC) staining. We report the first documented case of PMN (PLA2R positive) in a deceased kidney donor, transplanted to two different recipients and their clinical and immunological evolution through serial biopsies. Recipient A's first allograft biopsy (Day 26) was compatible with a MN with both positive PLA2R and IgG4 subepithelial deposits in IHC. The donor's preimplantation kidney biopsies were retrieved and reexamined, revealing MN, with high intensity for PLA2R and IgG4 in IHC. Recipient B's protocol allograft biopsy, performed later at 3 months, also revealed histology compatible with MN but without the presence of PLA2R nor IgG4 in IHC. At 1-year follow-up, both recipients maintain graft function. Serial protocol biopsies were performed in both patients showing disappearance of IgG4 in recipient A but the persistence of PLA2R in IHC. We can conclude that, given the reversal of PMN changes in the grafts, it could be considered to transplant a patient from an asymptomatic deceased donor with PMN as long as he maintains unaltered renal function.

Clinical Utility and Evolution of Donor Serum Lactate During Normothermic Regional Perfusion in Uncontrolled Donation After Circulatory Death.

BACKGROUND: Kidney transplantation from uncontrolled donor after circulatory death (uDCD) showed a higher incidence of delayed graft function and primary failure. The aim of this study was to study basal and kinetic evolution of lactate values in uDCD preserved on normothermic regional perfusion (NRP) as a predictive factor of kidney suitability exposed to prolong ischemic conditions. METHODS: Descriptive and prospective study of a cohort of out-of-hospital cardiac arrest patients admitted to the emergency room as potential uDCD. Donors meeting the inclusion criteria were preserved on NRP for at least 2 hours before procurement. Serum lactate levels were determined at arrival as basal level and at 30 minutes intervals and compared with adequate renal perfusion in the operating room (OR). RESULTS: Forty-five donors met inclusion criteria. Of these, 38 went to the OR (84.5%). No differences were found in basal lactate between accepted and rejected kidneys (203.08 ± 59.21 vs 175.43 ± 75.32 mg/dL, respectively); neither lactate, hematologic, hepatic transaminases, creatinine, or blood gas analysis sequential values evolved while on NRP. Lactate receiver operating characteristic curve failed to predict viability at different time points and did not correlate with the macroscopic kidney poor perfusion in the OR. CONCLUSIONS: The baseline and kinetic evolution of plasma lactate values while on NRP, were not useful tools to predict the final OR kidney viability owing to previous severe ischemic insult.

Outcomes From Brain Death Donors With Previous Cardiac Arrest Accepted for Pancreas Transplantation: A Single-center Retrospective Analysis.

OBJECTIVE: The aim of the study was to evaluate the effect of cardiac arrest time (CAT) in donors after brain death (DBD) donors on pancreas transplant outcome. SUMMARY OF BACKGROUND DATA: Results from donors after circulatory death report good outcomes despite warm ischemia times up to 57 minutes. Previous cardiac arrest in DBD has been addressed as a potential risk factor, but duration of the CAT has never been evaluated. METHODS: We conducted a retrospective analysis including 342 pancreas transplants performed at our center from 2000 to 2016, and evaluated the effect of previous cardiac arrest in DBD (caDBD) on pancreas transplant outcomes. RESULTS: A total of 49 (14.3%) caDBD were accepted for transplantation [median CAT of 5.0 min (IQR 2.5-15.0)]. Anoxic encephalopathy was most frequent and P-PASS higher (16.9 vs 15.6) in caDBD group when compared with other DBD. No differences were found in all other characteristics evaluated.Graft survival was similar between both groups, as was the incidence of early graft failure (EGF). CAT increased the risk for EGF [OR 1.09 (95% CI, 1.01-1.17)], and the duration of CPR discriminated for EGF [AUC of 0.86 (95% CI, 0.74-0.98)], with a sensitivity and specificity of 100% and 75% at a cutoff of 15 minutes. When evaluated separately, caDBD >15 min increased over 5 times the risk for EGF [HR 5.80 (95% CI, 1.82-18.56); P = 0.003], and these presented fewer days on the ICU (1.0 vs 3.0 d). CONCLUSION: CaDBD donors are suitable for routine pancreas transplantation without increasing EGF risk, and in those with longer CAT it may be prudent to postpone donation a few days to allow a thorough evaluation of organ damage following cardiac arrest.

Effect of Active and Early Possible Organ and Tissue Donor Detection in the Emergency Room in a University Hospital.

PURPOSE: The emergency room of the hospital is the gateway for patients with severe brain damage due to neurologic or cardiac conditions such as stroke or cardiac arrest. The main purpose is to design an active registry of patients, in the emergency room, to facilitate the detection and follow-up of potential donors according to their clinical evolution. MATERIAL AND METHODS: This is a 1-year prospective study from May 2017 to May 2018 with a register for detection of patients admitted to the emergency room with severe brain damage (Glasgow Coma Scale score ≤ 8), with active follow-up until hospital discharge, who might have died or otherwise become possible organ and tissue donors. RESULTS: One hundred sixty-six (107 men and 59 women) patients met the inclusion criteria: (1) 30.7% recovered from cardiac arrest; (2) 31.3% from stroke; (3) 16.9% from traumatic brain injury and multiple trauma; (4) 10.2% had decreased level of consciousness; (5) 4.8% had other cardiac conditions; and (6) 6.0% had other diagnoses. Seventy-seven out of 166 patients (46.4%) were evaluated as possible organ and tissue donors, with 37 out of 77 (48.0%) of the possible donors becoming real donors. This means that 37 out of 166 (22.3%) of the possible donors admitted to the emergency room became real donors. Twenty-two out of 77 of the patients (28.6%) evaluated had clinical contraindications for donation and in 18 out of 77 (23.4%), there was family refusal for any kind of organ or tissue donation. This record allowed the generation of the following organs and tissues: 4 hearts, 19 livers, 14 lungs, 52 kidneys, 2 pancreata, 29 corneas, 19 donations of bone allografts, 15 donations of skin tissue, 14 donations of valvular allografts, and 11 vascular allografts. CONCLUSIONS: The early and active possible donors registry at the emergency room has facilitated early detection and allow adequate follow-up and evaluation of possible organ and tissue donors.

The development of a predictive model of graft function in uncontrolled donors after circulatory death: validity of a pulsatile renal preservation machine cut-off value for kidney acceptance.

BACKGROUND: The criteria for kidney suitability in uncontrolled donors after circulatory death (uDCD) procured after regional normothermic perfusion are based on macroscopic appearance and renal haemodynamic values with final renal resistance (FRR). However, these criteria have not been analysed to predict the future graft function. This study presents a model to predict the outcome in uDCD kidneys and define the predictive FRR value. METHODS: All uDCD kidney transplants performed in our hospital from 2004 to 2016 were included. Donors and recipients and pre-transplantation data are described. The endpoint was glomerular filtration rate (GFR) ≥30 mL/min at 6 months after transplantation. RESULTS: A total of 194 recipients were included. FRR in donors ≥60 years old was (mean ± SD) 0.27 ± 0.11 versus 0.22 ± 0.09 mmHg/mL/min in donors <60 years (P = 0.042). Kidney survival was 88.2% versus 84% at 12 months and 60.7% versus 30.8% at 120 months (P = 0.067). For the group of recipients from donors ≥60 years, the FRR was 0.37 ± 0.08 mmHg/mL/min in the GFR <30 mL/min group versus 0.18 ± 0.06 mmHg/mL/min in the GFR ≥30 mL/min group (P < 0.001). The value FRR ≥0.3 mmHg/mL/min predicts 59-79% of GFR <30 mL/min [odds ratio = 2.16, 95% confidence interval (CI) 1.80-6.40; P < 0.001]. The predictive accuracy of FRR for GFR by ROC curve was 0.968 (95% CI). The best cut-off for FRR was 0.3 mmHg/mL/min to predict GFR at 6 months with a sensitivity of 67%, specificity of 100%, positive predictive value of 83% and negative predictive value of 92%. CONCLUSIONS: Our results suggest that in uDCD donors the combination of donor age ≥60 years together with FRR ≥0.3 mmHg/mL/min could predict poor outcome at 6 months after transplantation in low immunological risk recipients.

Safety and Tolerability of Alveolar Type II Cell Transplantation in Idiopathic Pulmonary Fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease with limited response to currently available therapies. Alveolar type II (ATII) cells act as progenitor cells in the adult lung, contributing to alveolar repair during pulmonary injury. However, in IPF, ATII cells die and are replaced by fibroblasts and myofibroblasts. In previous preclinical studies, we demonstrated that ATII-cell intratracheal transplantation was able to reduce pulmonary fibrosis. The main objective of this study was to investigate the safety and tolerability of ATII-cell intratracheal transplantation in patients with IPF. METHODS: We enrolled 16 patients with moderate and progressive IPF who underwent ATII-cell intratracheal transplantation through fiberoptic bronchoscopy. We evaluated the safety and tolerability of ATII-cell transplantation by assessing the emergent adverse side effects that appeared within 12 months. Moreover, pulmonary function, respiratory symptoms, and disease extent during 12 months of follow-up were evaluated. RESULTS: No significant adverse events were associated with the ATII-cell intratracheal transplantation. After 12 months of follow-up, there was no deterioration in pulmonary function, respiratory symptoms, or disease extent. CONCLUSIONS: Our results support the hypothesis that ATII-cell intratracheal transplantation is safe and well tolerated in patients with IPF. This study opens the door to designing a clinical trial to elucidate the potential beneficial effects of ATII-cell therapy in IPF.

Optimización del proceso de donación de tejidos en un hospital universitario: 10 años de experiencia / Optimising tissue donation process in a universiy hospital: 10 years of experience

Fundamento y objetivo: La necesidad de tejido para trasplante requiere un esfuerzo continuo en la detección y evaluación de las causas de fallecimiento de los sujetos potencialmente donantes de tejidos. El objetivo de este estudio fue evaluar la capacidad de optimizar la donación de tejidos tras la detección activa de fallecidos y la revisión exhaustiva de las causas de muerte de acuerdo con los estándares internacionales y locales de bancos de tejidos. Material y método. Desde el año 2002 se instauró un procedimiento de detección activa y precoz de fallecidos hospitalarios. Se estudió el incremento de potencialidad de donación modificando los criterios: edad (80 a 85 años), aceptación de facoemulsiones corneales, enfermedades autoinmunitarias y reevaluación de las sepsis. En la década 2002-2011 se mantuvieron los mismos criterios de exclusión absoluta. Se analizó la tasa de conversión de potenciales donantes a donantes reales de uno o varios tejidos. Resultados: Analizamos 16.531 fallecidos en parada cardiorrespiratoria. Cumplían criterios de exclusión absoluta 11.191 casos. La modificación de criterios incrementó los potenciales donantes: un 10,4% la edad, un 4,5% las enfermedades autoinmunitarias/facoemulsión y un 11,8% el criterio de sepsis (p < 0,00), con un incremento global del 16% (p < 0,00) al final del período de estudio. Se generaron un total de 2.371 donantes efectivos. La efectividad de generar donantes pasó del 11 al 21% durante la década (p < 0,00). Conclusiones: La combinación de un sistema de detección proactiva del fallecimiento y la revisión continua de los criterios de aceptación para cada tipo de tejido permite, en un medio hospitalario, incrementar el número de potenciales donantes (AU)

Background and objective: The demand of tissue for transplants requires a continuous effort in detecting potential donors and assessing the causes of death. We aimed to assess the capacity to optimise tissue donation rates with the implementation of an active detection system of hospital deaths alongside a comprehensive assessment of the causes of death according to current international and local tissue banks’ standards. Material and method: An early and pro-active detection programme of hospital deaths was implemented in 2002. The potential increase in donation was analysed according to modified criteria: age (80 to 85 years), acceptance of corneal phacoemulsification, autoimmune diseases, and sepsis reassessment. During the 2002-2011 decade, the criteria for absolute exclusion remained the same. The conversion rate from potential donors to actual donors of one or more tissue types was analysed. Results: A total of 16.531 cases of cardiac arrest were analysed, and 11.191 of the cases fulfilled criteria of absolute exclusion. The modification of criteria led to an increase of potential donors: 10.4% age factor, 4.5% autoimmune diseases/phacoemulsification factor, 11.8% sepsis factor (P < .00). The study indicated a total increase of 16% (P < .00). A total of 2.371 successful donations were generated. The efficiency to generate donors increased from 11 to 21% during the aforementioned decade (P < .00). Conclusion: A pro-active detection system of hospital deaths combined with a continuous re-assessment of the acceptance criteria for each tissue type in the hospital setting leads to an increase in the potential donors’ rate (AU)

[Optimising tissue donation process in a university hospital: 10 years of experience]. / Optimización del proceso de donación de tejidos en un hospital universitario: 10 años de experiencia.

BACKGROUND AND OBJECTIVE: The demand of tissue for transplants requires a continuous effort in detecting potential donors and assessing the causes of death. We aimed to assess the capacity to optimise tissue donation rates with the implementation of an active detection system of hospital deaths alongside a comprehensive assessment of the causes of death according to current international and local tissue banks' standards. MATERIAL AND METHOD: An early and pro-active detection programme of hospital deaths was implemented in 2002. The potential increase in donation was analysed according to modified criteria: age (80 to 85 years), acceptance of corneal phacoemulsification, autoimmune diseases, and sepsis reassessment. During the 2002-2011 decade, the criteria for absolute exclusion remained the same. The conversion rate from potential donors to actual donors of one or more tissue types was analysed. RESULTS: A total of 16.531 cases of cardiac arrest were analysed, and 11.191 of the cases fulfilled criteria of absolute exclusion. The modification of criteria led to an increase of potential donors: 10.4% age factor, 4.5% autoimmune diseases/phacoemulsification factor, 11.8% sepsis factor (P<.00). The study indicated a total increase of 16% (P<.00). A total of 2.371 successful donations were generated. The efficiency to generate donors increased from 11 to 21% during the aforementioned decade (P<.00). CONCLUSION: A pro-active detection system of hospital deaths combined with a continuous re-assessment of the acceptance criteria for each tissue type in the hospital setting leads to an increase in the potential donors' rate.

Presente y futuro de la donación y trasplante de órganos: ¿nos enfrentamos a la crisis del «Modelo Español»? / Present and future of organ donation and transplantation: are we confronting a crisis in the “Spanish Model”?

La donación y trasplante de órganos se enfrenta a nuevos escenarios que pueden inducir la crisis del llamado «Modelo Español». El descenso de los accidentes de tráfico; las campañas de prevención de los factores de riesgo cardiovascular; la mejoría en el tratamiento médico y quirúrgico del paciente neurocrítico; la aplicación de protocolos de «limitación del tratamiento de soporte vital» al final de la vida; el control del ingreso de pacientes sin pronóstico vital en Urgencias; la actuación precoz desde los Servicios de Emergencia extrahospitalarias en el manejo de los pacientes isquémicos con la implementación de protocolos desde la creación de los «códigos infarto agudo de miocardio» o las Unidades de Ictus; son factores que pueden causar descenso de la potencialidad de donación con la consiguiente pérdida del liderazgo mundial si no se produce un proceso de reinvención por parte de las instituciones y del personal involucrado a pesar de las circunstancias médicas y socioeconómicas actuales(AU)

New challenges confronting the process of organ donation and transplantation could lead to a crisis situation in the so called “Spanish Model”. The reduction in traffic accidents; better campaigns to prevent cardiovascular risk factors; improvement in the medical and surgical approach of neurocritical patients; application of protocols for withdrawal of therapeutic efforts together with a restricted hospitalization of patients without vital prognosis performed in Emergency Departments; better acute management of ischaemic patients in extra-hospital emergencies, together with the development of Acute Myocardial Infarction and Stroke Units, are all factors that could have a negative impact in potential organ donors and threaten Spain‘s leadership if the institutions and personnel involved do not work to reinvent the process by confronting the medical and socioeconomic circumstances(AU)

Recommendations for management of Chagas disease in organ and hematopoietic tissue transplantation programs in nonendemic areas.

The substantial immigration into Spain from endemic areas of Chagas disease such as Latin America has increased the number of potential donors of organs and tissues. In addition, an increasing number of patients with advanced Chagas heart disease may eventually be eligible to receive a heart transplant, a universally accepted therapeutic strategy for the advanced stages of this disease. Therefore, it is necessary to establish protocols for disease management. This document is intended to establish the guidelines to be followed when a potential donor or a tissue or organ recipient is potentially affected by Chagas disease and summarizes the action criteria against the possibility of Chagas disease transmission through the donation of organs, tissues, or hematopoietic stem cells and aims to help professionals working in this field. A single registry of transplants in Trypanosoma cruzi infected donors and/or recipients will provide and disseminate experience in this area, which has shown a low recorded incidence to date.