Low Risk of Anti-Human Leukocyte Antigen Antibody Sensitization After Combined Kidney and Islet Transplantation

Abstract

Anti-human leukocyte antigen (HLA) antibody could lead to humoral rejection and a decrease in graft survival after kidney transplantation. A recent report has suggested that islet transplantation alone is associated with a high rate of sensitization. The withdrawal of the immunosuppressive therapy because of the progressive nonfunction of the islets could explain the high rate of sensitization. Because the specific risk of immunization of multiple islet infusions remains unknown, we studied the immunization rate in our cohort of multiple islet infusions transplant recipients. De novo anti-HLA antibodies were analyzed in 37 patients after islets alone (n=8), islet-after-kidney (n=13), and simultaneous islet-kidney (n=16) transplantation by solid phase assays over time. The rate of immunization was 10.8% that is comparable with the risk of immunization after kidney transplantation alone. Multiple islet infusions do not represent a specific risk for the development of anti-HLA antibodies after combined kidney-islets transplantation.

Evidence for Humoral Rejection of a Pancreatic Islet Graft and Rescue with Rituximab and IV Immunoglobulin Therapy

“…The development of such antibodies precedes graft failure in kidney, heart and lung transplantation (6,7). Although previous reports suggest that the same may be true for islet transplantation, it is difficult to prove because numerous factors influence graft function (11)(12)(13)(14) …”

Kidney, Pancreas and Islet Transplant Options for Patients with Diabetic Nephropathy

“…Nevertheless, these first encouraging results could not be fully reproduced by other centers and patients needed multiple islet transfusions with a long-term success below 10% [53][54][55]. In addition, the immunosuppressive protocols are potentially nephrotoxic and may be accompanied with a deterioration of the renal function [56,57], whereas the failed islet grafts may lead to recipients' alloimmunization (sensitization) by the production of de novo anti-HLA antibodies in titers ranging between 10.8%-31% [56][57][58]. These poor results have raised skepticism in the transplant community [59] and today only a few centers continue islet transplants on a regular basis [54,55].…”

“…Regarding IT, the main obstacles are the rather poor long-term results regarding insulin independence, the need for long-term immunosuppression and its risks (infections, malignancies etc. ), the possible more rapid deterioration of the renal function due to nephrotoxicity (calcineurin inhibitors) and the risk of alloimmunization [53][54][55][56][57][58]. However, successful IT has also been associated with significant benefits, such as stabilization or even improvement of retinopathy and neuropathy [54,55].…”

“…Although the ultimate goal of islet transplantation would be to achieve insulin independence, this can be done rarely and the current goals focus mainly on protection from hypoglycemia, reduction of the daily dose of insulin and correction of HbA1c [54,55]. Due to all the above reasons, islet transplantation should be still considered as an experimental procedure performed only in experienced transplant centers and it is currently recommended only for well informed T1DM patients with difficult to control diabetes and well preserved renal function, or already immunosuppressed T1DM patients undergoing simultaneous islet-kidney transplantation, islet transplantation after SPK and failure of the pancreas graft, or islet transplantation following a successful kidney transplant [54,57]. As there is also a limited pool of donors for pancreata, islet transplantation research is now focusing on alternative resources such as stem cells or xenogeneic (porcine) islets [54,62].…”

Pancreas Versus Islets After a Successful Kidney Transplant

“…Indeed, with T-depletional inductive immunosuppression and tacrolimus-based immunosuppression, this concern has largely been eliminated in recent islet transplant experience [32]. The risk has also been low in SIK transplantation [56,67].…”