Tuberculosis treatment without rifampin in kidney/kidney-pancreas transplantation: A case series report.

BACKGROUND: The best approach to tuberculosis (TB) treatment in transplanted patients is still unknown. Current guidelines are based on evidence either extrapolated from other populations or observational. Rifampin-containing regimens have strong pharmacokinetic interactions with immunosuppressive regimens, with high rates of organ dysfunction and ∼20% mortality. This report describes the results obtained using non-rifampin-containing regimens to treat confirmed TB in adult patients with kidney/kidney-pancreas transplantation. METHODS: Retrospective data analysis from confirmed TB cases in adult kidney/kidney-pancreas transplant recipients (2006-2019), treated "de novo" with non-rifampin-containing regimens. RESULTS: Fifty-seven patients had confirmed TB. Thirty patients were treated "de novo" with non-rifampin-containing regimens. These patients' mean age was 49.24 (±11.50) years. Induction immunosuppression was used in 22 patients. Maintenance immunosuppression was tacrolimus-mycophenolate-steroids in 13 (43%), sirolimus-mycophenolate-steroids in 6 (20%), and other immunosuppressive regimens in 11 (36%). Belatacept was used in four patients. TB localizations: pulmonary 43%; disseminated 23%; extrapulmonary 33%. Twenty-seven (90%) patients completed treatment with isoniazid, ethambutol, and levofloxacin (12 months, 23; 9 months, 3; 6 months, 1); 12 of these patients also received pyrazinamide for the first 2 months and were cured with functioning grafts. One patient (3%) lost the graft while on treatment. Two patients (7%) died while on TB treatment. Median (range) follow-up after completion of TB treatment was 32 (8-150) months. No TB relapses were observed. CONCLUSIONS: Results with non-rifampin-containing TB treatments in this case series were better (in terms of mortality and graft dysfunction) than those previously described with rifampin-containing regimens in transplanted patients.

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.

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.