ABSTRACT
El trasplante renal constituye la mejor opción de tratamiento para los pacientes con enfermedad renal crónica terminal. La supervivencia del injerto es de gran importancia y puede ser afectada por factores inmunológicos o no inmunológicos; esto unido al número de pacientes en las listas de espera, hace necesario definir estrategias de manejo que permitan tener mejores resultados a largo plazo. Objetivo. Determinar las características clínicas y humorales, y los desenlaces en receptores de trasplante renal o combinado hígado-riñón, altamente sensibilizados, que recibieron profilaxis combinada con inmunoglobulina intravenosa y plasmaféresis en el Hospital San Vicente Fundación, en Colombia. Materiales y métodos. Se realizó un estudio retrospectivo, observacional, descriptivo, que incluyó los pacientes trasplantados entre el 4 de julio de 2010 y el 19 de abril de 2017. Como variables se incluyeron, entre otras, la etiología de la enfermedad renal crónica, el tipo de terapia recibida, y el tiempo en lista de espera en días. Como desenlace se evaluó la presencia de rechazo, el tipo de rechazo, la pérdida del injerto, las complicaciones y la muerte. Resultados. Del total de 25 pacientes, el 100% recibió inmunoglobulina intravenosa y el 84% plasmaféresis. El 12% presentó rechazo del injerto, todos de tipo humoral, y el 20% perdió el injerto. Discusión. A pesar de la gran variedad de protocolos propuestos en la literatura, en esta población especial no se ha establecido un protocolo óptimo de inmunosupresión. El protocolo en nuestra pequeña cohorte no tuvo un impacto negativo en el porcentaje de infecciones postrasplante ni en la pérdida del injerto renal, pero sí redujo el tiempo en las listas de espera; por lo tanto, se requieren estudios adicionales para confirmar los hallazgos encontrados en este estudio
Kidney transplantation is the best treatment option for patients with terminal chronic kidney disease, regardless of the etiology, making graft survival an important feature, which may be affected by immunological or non-immunological factors. This, added to the increasing number of patients on waiting lists, makes it necessary to define management strategies for these patients that allow better long-term results. Objectives. To determine the clinical, humoral and outcome characteristics in highly sensitized recipients of kidney and simultaneous kidneyliver transplant who received combined prophylaxis with intravenous immunoglobulin and plasmapheresis therapy in a Colombian medical center. Materials and methods. A retrospective, observational, descriptive study was carried out that included the transplanted patients between July 4, 2010 and April 19, 2017. Variables included the etiology of chronic kidney disease, the type of therapy received, and waiting time in days, among others. As outcomes, the presence of rejection, type of rejection, graft loss, complications and death were evaluated. Results. From a total of 25 patients, 100% received intravenous immunoglobulin and 84% plasmapheresis. Twelve percent presented graft rejection, all humoral, and 20% lost the graft. Discussion. Despite the great variety of protocols proposed in the literature, an optimal immunosuppression protocol has not been established for this particular population. The protocol in our small cohort did not have a negative impact on the percentage of post-transplant infections nor in the loss of the renal graft, but it did reduce waiting time; therefore, additional studies are required to confirm the findings in this study
Subject(s)
Kidney Transplantation , Plasmapheresis , Complement Activation , Graft RejectionABSTRACT
Objective To explore the feasibility and safety of kidney transplantation for pre-sensitized infants using deceased donors and summarize the relevant literature reports .Methods A second kidney transplantation was successfully performed for an 8-month-old pre-sensitized girl in July 2017 .She had a low level of donor specific antibody (DSA ) against human leucocyte antigen (HLA ) B62 due to severe acute rejection (AR) after her first kidney transplantation .For desensitization , plasmapheresis and intravenous immunoglobulin plus anti-CD20 antibodies were offered on operative day .Clinical data and outcomes were retrospectively analyzed .Results Renal graft regained immediate function after transplantation .Preformed DSA could be detected at 1 week .However ,there was no de novo DSA .At 1 year post-transplantation ,preformed DSA turned negative .During a follow-up period of 2 years ,renal graft showed an excellent function with a serum creatinine of 31 μmol/l and eGFR of 110 ml/min/1 .73m2 .No AR episode or proteinuria occurred .DSA stayed negative .Simultaneously physical development also caught up .Her height of 93 cm tall and weight of 13 .5 kg at month 24 & 8 months corresponded to normal grow th curve of her age .Conclusions Pre-sensitized infant could tolerate desensitization therapy well and achieve satisfactory outcomes .With surgical precisions and optimized managements ,kidney transplantation provides excellent renal functions and survivals for infants with organs from deceased donors .
ABSTRACT
Objective To explore the feasibility and safety of kidney transplantation in highly sensitized recipients by using ABO incompatible (ABOi) and yet human leucocyte antigen (HLA) supremely matched deceased donor kidneys and summarize the literatures as well .Methods A kidney graft from a deceased donor of blood type B was transplanted to a highly presensitized recipient of blood type O to achieve a HLA matching number of 7 /8 in May 2018 .Donor specific antibody (DSA) against HLA was negative and baseline anti-B IgM 1 : 16 . Plasmapheresis (PP) plus intravenous immunoglobulin (IVIG) plus anti-CD20 antibodies were offered on operation day .Clinical data was retrospectively analyzed .Results Renal graft functioned immediately and achieved a normal level of serum creatinine (SCr) at d2 after transplantation .However ,the value of SCr increased to 131 μmol/ l at d9 with a simultaneously elevated level of anti-B IgM from 1:2 at d7 to 1:16 .A renal graft biopsy at d11 showed mild inflammation in peritubular capillaries and focal tubulitis with minimal interstitial infiltration .No de novo DSA was detected .Then PP plus IVIG were then given twice ,followed by an administration of IVIG alone for another 2 days (20 g/d) .After treatments ,SCr had a range of 120- 140 μmol/l and anti-B IgM level decreased to 1:4 at d21 post-transplantation .During a follow-up of 6 months ,there was no onset of proteinuria or infection and the last value of SCr was 114 μmol/L . Conclusions In HLA highly sensitized recipients awaiting for transplant opportunities , successful prevention of HLA antibodies-mediated rejection may be achieved by using ABO incompatible and yet HLA compatible deceased donors .
ABSTRACT
Circulating alloantibodies are found in a substantial number of renal allograft recipients, and can induce chronic allograft injury, which is represented microscopically as transplant glomerulopathy and diffuse C4d deposition in peritubular capillaries (PTCs). Development of these injuries is significantly correlated with late allograft loss, and in this regard, it was included as a new disease entity named chronic antibody-mediated rejection (cAMR) in the updated Banff 05 classification. Usually, the prognosis of cAMR is poor and conventional immunosuppressants mainly targeting T cell-mediated immunity cannot prevent or reverse it. Therefore, some researchers have suggested that therapies directed at the humoral response may be required for the treatment of cAMR. Recently, some reports have suggested that the combined use of rituximab and intravenous immunoglobulin (IVIg) therapy may be useful for the treatment of cAMR. Our previous study also showed that rituximab and IVIg combination therapy effectively delayed the progression of cAMR. We administered rituximab and IVIg combination therapy to 18 biopsy-proven cAMR patients and found that it significantly slowed the decline of the estimated glomerular filtration rate. However, this effect was limited in patients with heavy proteinuria, and dissipated in all patients by 1 year post-treatment. Recently, new drugs targeting the humoral immune system, such as bortezomib and eculizumab, have been tested for the treatment of cAMR. However, the studies still lack definitive data in terms of successful treatment of cAMR. We speculate that those therapies will compensate for the limitation of previous anti-humoral therapies for cAMR.
Subject(s)
Humans , Allografts , Capillaries , Classification , Glomerular Filtration Rate , Immune System , Immunity, Cellular , Immunoglobulins , Immunoglobulins, Intravenous , Immunosuppressive Agents , Isoantibodies , Kidney Transplantation , Pathology , Prognosis , Proteinuria , Bortezomib , RituximabABSTRACT
Objective To determine the roles of MyD88 and Trif,critical adaptor proteins for TLR signaling,in production of donor-specific antibodies (DSA) and memory T cells in a presensitized mouse cardiac transplant model.Methods Skin grafts from Balb/c mice were transplanted into either wild type B6 mice or B6 Myd88 and Trif double knockout mice (Myd88/Trif DKO).The recipients were subsequently transplanted heterotopically with cardiac grafts from the same donors two weeks after skin transplantation.Plasma DSA levels and spleen phenotypical analysis were performed prior to heart transplant or at time of cardiac rejection by using flow cytometry.Results Recipients presensitized with skin grafts developed accelerated cardiac allograft rejection in the absence of Myd88 and Trif.However,plasma DSA,especially IgG2,was significantly decreased (P＜0.05) in Myd88/Trif DKO mice,compared to that in Wild Type mice at 2nd week after skin transplantation.The production of DSAs including all IgG subtypes was further reduced 3 days following heart transplantation in the Myd88/Trif DKO.In addition,MyD88/Trif DKO mice had impaired ability to generate memory T cells,as percentages of both CD44hi CD4+ and CD44hi CD8+ were significantly lower in the DKO than in Wild Type mice (P＜0.01,P＜0.05).Conclusion Simultaneous ablation of MyD88 and Trif in recipients significantly decreases the production of serum DSAs and spleen memory T cells following allogeneic skin and heart transplantation,supporting a crucial role of TLR signaling in adaptive immune responses in organ transplantation.
ABSTRACT
OBJECTIVE: The significance of pretransplant, donor-specific antibodies on long-term patient outcomes is a subject of debate. This study evaluated the impact and the presence or absence of donor-specific antibodies after kidney transplantation on short- and long-term graft outcomes. METHODS: We analyzed the frequency and dynamics of pretransplant donor-specific antibodies following renal transplantation from a randomized trial that was conducted from 2002 to 2004 and correlated these findings with patient outcomes through 2009. Transplants were performed against a complement-dependent T- and B-negative crossmatch. Pre- and posttransplant sera were available from 94 of the 118 patients (80%). Antibodies were detected using a solid-phase (LuminexH), single-bead assay, and all tests were performed simultaneously. RESULTS: Sixteen patients exhibited pretransplant donor-specific antibodies, but only 3 of these patients (19%) developed antibody-mediated rejection and 2 of them experienced early graft losses. Excluding these 2 losses, 6 of 14 patients exhibited donor-specific antibodies at the final follow-up exam, whereas 8 of these patients (57%) exhibited complete clearance of the donor-specific antibodies. Five other patients developed ''de novo'' posttransplant donor-specific antibodies. Death-censored graft survival was similar in patients with pretransplant donor-specific and non-donor-specific antibodies after a mean follow-up period of 70 months. CONCLUSION: Pretransplant donor-specific antibodies with a negative complement-dependent cytotoxicity crossmatch are associated with a risk for the development of antibody-mediated rejection, although survival rates are similar when patients transpose the first months after receiving the graft. Our data also suggest that early posttransplant donor-specific antibody monitoring should increase knowledge of antibody dynamics and their impact on long-term graft outcome.
Subject(s)
Adolescent , Adult , Female , Humans , Middle Aged , Young Adult , Antibodies/immunology , Blood Grouping and Crossmatching , Graft Rejection/immunology , Graft Survival/immunology , Kidney Transplantation/immunology , Tissue Donors , Cross-Sectional Studies , Cyclosporine/therapeutic use , Follow-Up Studies , Graft Rejection/prevention & control , HLA Antigens/immunology , Immunosuppressive Agents/therapeutic use , Kidney Transplantation/adverse effects , Tacrolimus/therapeutic useABSTRACT
El trasplante renal es el tratamiento de elección para los pacientes con falla renal terminal. Las principales causas de pérdida de injertos son la muerte del paciente con injerto funcionante, especialmente de causa cardiovascular y la nefropatía crónica del injerto, con una pérdida crónica de injertos que resulta en un problema relevante. Dentro de las causas de nefropatía crónica destaca la causa inmunológica. Una de las causas de pérdida de injertos de origen inmunológico son los rechazos agudos, los que pueden ser de origen celular y humoral. Por otra parte, y a pesar de los avances en la comprensión de los mecanismos responsables de la inmunidad celular y el desarrollo de nuevas drogas inmunosupresoras (DIS), el rechazo mediado por anticuerpos o humoral aparece hoy como un peligro para la sobrevida del injertos a corto y a largo plazo. Afortunadamente el tratamiento del rechazo agudo humoral con drogas específicas ha resultado exitoso, sin embargo no ha ocurrido lo mismo con el rechazo mediado por anticuerpos de presentación más tardía, posiblemente por su comportamiento subclínico y un diagnóstico tardío, permaneciendo como un nuevo desafío recientemente reconocido. Por otra parte y basado en el exitoso tratamiento del RAH, se ha planteado mejorar las expectativas de llegar a realizar un trasplante a los pacientes sensibilizados. Esto es posible conseguir aplicando protocolos de desensibilización que se basan en la utilización de las mismas drogas para tratar RAH, consiguiendo ampliar las posibilidades de trasplante. El éxito de éstas es relativo al tipo de protocolos y a la intensidad de la sensibilización. La sobrevida del injerto en esta situación es plausible en la gran mayoría de los casos, sin embargo existe riesgo de presentar rechazo agudo humoral, y más complejo aún es el hecho que la sobrevida a largo plazo de los injertos sigue siendo todavía desconocida.
Renal Transplantation is the therapy of choice for patients with end-stage renal failure. The main causes for graft losses are patient death with functioning graft, mainly of cardiovascular etiology and chronic allograft nephropathy. Among the causes of chronic allograft nephropathy, the immunological ones are among the most important; one of them are the acute rejection episodes, which can be of cellular or humoral etiology; in addition, and despite the understanding of the mechanisms responsible for the cell immunity and the development of new immunosuppressive drugs (DIS) the antibody mediated rejection o humoral rejection has become today a danger for the short and long term allograft survival. Fortunately, the treatment of acute humoral rejection with specific drugs has become successful, however, the situation is different with late occurring antibody mediated rejection episodes, probably due to its subclinical behavior and a late diagnosis, remaining as a new challenge recently recognized. On the other hand based on the successful treatment of the RAH, expectations of performing a transplant in sensitized patients have been improved. This is possible to achieve using desensitizing protocols base don the same drugs used to treat RAH, thus increasing transplant possibilities. The success is related to the type of protocols and the intensity of the desensitizing. Graft survival in this situation is possible in the large majority of cases, however, the risk of acute humoral rejection is present, but even more complex is the fact thatlong-term survival is still unknown.