Anti-Hla donor-specific antibody monitoring in pancreas transplantation: Role of protocol biopsies.

In kidney transplantation, de novo donor-specific antibodies (DSA) correlate with poor graft survival, and Consensus Guidelines recommend a protocol biopsy. In pancreas transplantation, DSA are also associated with poor graft outcomes; however, there are no recommendations on protocol biopsies. We started an antibody screening protocol on pancreas transplant patients at 0, 3, 6, 12 months, and yearly. Patients with DSA or high MFI non-DSA were considered for protocol biopsies of both organs. Results: 143 pancreas recipients were screened. 84 patients had negative antibodies throughout the study, 11 patients were found to have antibodies at graft dysfunction, and 48 patients had positive antibodies at screening without acute organ dysfunction (study group). Among the 30 non-DSA patients, 9 had protocol simultaneous pancreas and kidney biopsies performed with negative results in all of them. In contrast, among the 18 DSA patients, 15 had these biopsies performed, and 47% presented with subclinical rejection of the kidney, the pancreas, or both. In addition, some of the DSA patients without a protocol biopsy presented with rejection during the first 15 months of follow-up. Conclusion: We conclude that protocol biopsies of both grafts may play a role in the follow-up of pancreas transplant patients with de novo DSA appearance.

Gene expression profile in delay graft function: inflammatory markers are associated with recipient and donor risk factors.

BACKGROUND: Delayed graft function (DGF) remains an important problem after kidney transplantation and reduced long-term graft survival of the transplanted organ. The aim of the present study was to determine if the development of DGF was associated with a specific pattern of inflammatory gene expression in expanded criteria of deceased donor kidney transplantation. Also, we explored the presence of correlations between DGF risk factors and the profile that was found. METHODS: Seven days after kidney transplant, a cDNA microarray was performed on biopsies of graft from patients with and without DGF. Data was confirmed by real-time PCR. Correlations were performed between inflammatory gene expression and clinical risk factors. RESULTS: From a total of 84 genes analyzed, 58 genes were upregulated while only 1 gene was downregulated in patients with DGF compared with no DGF (P = 0.01). The most relevant genes fold changes observed was IFNA1, IL-10, IL-1F7, IL-1R1, HMOX-1, and TGF-ß. The results were confirmed for IFNA1, IL-1R1, HMOX-1 and TGF-ß. A correlation was observed between TGF-ß, donor age, and preablation creatinine, but not body mass index (BMI). Also, TGF-ß showed an association with recipient age, while IFNA1 correlated with recipient BMI. Furthermore, TGF-ß, IFNA1 and HMOX-1 correlated with several posttransplant kidney function markers, such as diuresis, ultrasound Doppler, and glycemia. CONCLUSIONS: Overall, the present study shows that DGF is associated with inflammatory markers, which are correlated with donor and recipient DGF risk factors.

Estado actual del trasplanterenopancreático / Current status of the kidney-pancreas transplant

RESUMEN El trasplante de páncreas es un tratamiento alternativo para la diabetes. Sus modalidades e indicaciones son: 1) trasplante de páncreas simultáneo con riñón para pacientes con diabetes mellitus tipo 1 o con nefropatía diabética en estadio terminalen tratamiento sustitutivo o próximo al mismo; 2) trasplante de páncreas después de riñón parapacientes condiabetes mellitustipo 1 con un trasplante renal funcionante; 3) trasplante de páncreas aislado parapacientes con diabetes mellitustipo 1 con hipoglucemias aperceptivas que requieren internaciones o rescate de terceros. Algunos pacientes con diabetes mellitus tipo 2 seleccionados pueden ser candidatos a trasplante de páncreas. La selección de donantes es muy importante, el donante ideal es fallecido por traumatismo craneoencefálico, menor de 45 años, con un peso entre 30 y 90 kg, con un IMC menor a 30kg/m2, hemodinámicamente estable y sin antecedentes de paro cardiorespiratorio ni hipotensión sostenida. Hay varias estrategias de derivación de la función endócrina (sistémica y portal) y exócrina (entérica o vesical), la más utilizada es la derivación sistémica y entérica. En el manejo perioperatorio se destacan estrategias para mantener una buena presión de perfusión tisular, un control estricto de glucemia, para prevenir la trombosis del injerto debe implementarse un plan de antiagregación y anticoagulación, todo lo anterior junto a una profilaxis antibiótica, antifúngica y antiviral. Los esquemas clásicos de inmunosupresión incluyen una inducción con esteroides y anticuerpos deplecionantes de linfocitos T y un mantenimiento con un triple esquema con esteroides, tacrolimus y micofenolato. La clasificación de Banffdistingue rechazos celulares y humorales. La base del tratamiento del rechazo celular incluye pulsos de esteroides y anticuerpos deplecionantes de linfocitos T, mientras que los rechazos humorales requieren de plasmaféresis e inmunoglobulina endovenosa. Las principales complicaciones postoperatorias son el sangrado, la pancreatitis, la trombosis del injerto y las fístulas anastomóticas. En cuanto a los resultados, el trasplante de páncreas presenta, a cinco años, una supervivencia del paciente del 90% y un 77% del injerto pancreático. Las modalidades de trasplante solitario presentan menor supervivencia alejada del injerto. En Argentina hay una actividad de trasplante de páncreas de entre 60 y 80 trasplantes anuales. La reglamentación del INCUCAIprevé la inscripción anticipada en lista de espera de pacientes con nefropatía terminal con depuración de creatinina menor a 30ml/min.

ABSTRACT Pancreas transplantation is an alternative treatment for diabetes. Its modalities and indications are the following: 1) simultaneous pancreas and kidney transplantation: type 1 diabetes mellitus patients with end-stage diabetic nephropathy (in replacement treatment or close to it); 2) pancreas transplantation after kidney: type 1 diabetes mellitus patients with a functioning kidney transplant; 3) isolated pancreas transplantation: type 1 diabetes mellitus patients with unperceived hypoglycemia requiring hospitalization or rescue by third parties. Some of the screened type 2 diabetes mellitus patients may be pancreas transplantation candidates. Choosing a donor is very important: the ideal donor should be a deceased one who died due to intracranial injury, under 45 years of age, weighing between 30 and 90 kg, with a BMI below 30kg/m2, hemodynamically stable and having no history of cardiopulmonary arrest or sustained hypotension. There exist various strategies to divert the endocrine function (systemic and portal) and the exocrine function (vesical or enteric), systemic and enteric diversion being the most commonly used. Among the techniques which stand out during perioperative management, we could mention maintaining a good tissue perfusion, a strict glycemic control, an antiaggregation/anticoagulation plan to prevent graft thrombosis and antibiotic, antifungal and antiviral prophylactic treatment. Classic immunosuppression schemes consist of induction with T cell depleting steroids and antibodies and keeping a three-drug treatment including steroids, tacrolimus and mycophenolate. Banff classification draws a distinction between cellular and humoral rejection. The basis for cellular rejection treatment includes steroid-pulse therapy and T-cell depleting antibodies, while humoral rejection requires plasmapheresis and endovenous immunoglobulin. The main postoperative complications are bleeding, pancreatitis, graft thrombosis and anastomosis fistula. As for the results, the survival rate 5 years after pancreas transplantation is 90% for patients and 77% for pancreatic grafts. Isolated transplantation presents a lower long-term survival of the graft. In Argentina, between 60 and 80 pancreas transplants are performed every year. INCUCAI regulations provide for early registration on the waiting list for patients suffering from end-stage nephropathy with a creatinine clearance lower than 30 mL/min.

Diabetes mellitus post transplante / Post transplant Diabetes mellitus

El creciente aumento del transplante de órganos sólidos como alternativa terapéutica a diferentes enfermedades se acompaña de un incremento en la prevalencia de diabetes mellitus post transplante.Aunque la sobrevida del injerto y del paciente después del transplante de un órgano sólido ha mejorado en los últimos años, los receptores de transplante continúan mostrando una mayor prevalencia de enfermedad cardiovascular en comparación con la población general. Los factores que determinan esto último son la hipertensión arterial, la dislipidemia y la diabetes mellitus. Entre ellos, la diabetes mellitus post transplante se ha identificado como uno de los factores más importantes que, además del aumento de mortalidad cardiovascular, también reduce la función del injerto, aumenta el riesgo de infecciones e incrementa el porcentaje de pérdida del injerto.Existen varios factores de riesgo asociados a esta enfermedad. Dentro de los potencialmente modificables se encuentra la presencia de síndrome metabólico y obesidad antes del transplante. Entre los no modificables figuran el antecedente de diabetes mellitus tipo 2 en familiar de primer grado, la edad mayor de 40 años, y la coinfección con virus de hepatitis C. También la predisposición a desarrollar esta patología está vinculada con el tipo de inmunosupresión recibida. Los corticoides y los inhibidores calcineurínicos (Ciclosporina y Tacrolimus) son drogas con una gran capacidad diabetogénica.En el año 2003 se publicaron las Normas de Consenso Internacional sobre Diabetes de Novo Post Transplante, estableciéndose que el diagnóstico se realiza según los criterios de la Asociación Americana de Diabetes. Asimismo se fijó utilizar el algoritmo de tratamiento para diabetes mellitus tipo 2, teniendo en cuenta las posibles interacciones con las drogas inmunosupresoras y los eventuales efectos adversos de las mismas. A pesar de ello, la mayoría de los pacientes con DMPT requieren tratamiento con insulina.Debemos recordar...

The increasing amount of solid organs transplantation as a therapeutic alternative in different diseases is accompanied by an increase in the prevalence of post transplantation diabetes mellitus. Despite last years improvement of graft and patient over-life after solid organ transplantation, the receivers continue showing an important prevalence of cardiovascular disease in comparison with the general population. The factors which determine this condition are the hypertension, hyperlipidemia, and diabetes mellitus. Among them, the post-transplantation diabetes mellitus has been identified like one of the most important factors that in addition to the increase of cardiovascular mortality, also reduces the graft function, increases the risks of infections and the percentage of graft loss...