Pancreas-After-Islet Transplantation in Nonuremic Type 1 Diabetes: A Strategy for Restoring Durable Insulin Independence

Abstract

Islet transplantation offers a minimally-invasive approach for beta cell replacement in diabetic patients with hypoglycemic unawareness. Attempts at insulin independence may require multiple islet re-infusions from distinct donors, thus increasing the risk for allogeneic sensitization. Currently, solid organ pancreas transplant is the only remaining surgical option following failed islet transplantation in the US. However, the immunologic impact of repeated exposure to donor antigens on subsequent pancreas transplantation is unclear. Here we describe a case series of seven patients undergoing solid organ pancreas transplant following islet graft failure, with long-term follow-up of pancreatic graft survival and renal function. Despite highly variable panel-reactive antibody (PRA) levels prior to pancreas transplant (mean 27±35%), all seven patients achieved stable and durable insulin independence with a mean follow-up of 6.7 years. Mean hemoglobin A1c (HgbA1c) values improved significantly from post-islet, pre-pancreas levels (mean 8.1±1.5%) to post-pancreas levels (mean 5.3±0.1%; p=0.0022). Three patients experienced acute rejection episodes successfully managed with thymoglobulin and methylprednisolone, and none of these pre-uremic type 1 diabetic recipients developed Stage 4 or 5 chronic kidney disease postoperatively. These results support pancreas-after-islet (PAI) transplantation with aggressive immunosuppression and protocol biopsies as a viable strategy to restore insulin independence after islet graft failure.

Long-term Persistence of Allosensitization After Islet Allograft Failure

“…Several studies suggest that pancreas after islet transplantation can be a successful strategy to achieve long-term insulin independence in previously failed islet allograft recipients. 12,37 However, allosensitization remains of concern given the prolonged wait time for subsequent transplantation. 37,38…”

Response to Treatment for Chronic-active T Cell–mediated Rejection in Kidney Transplantation: A Report of 3 Cases

“…However, if the most important aspect of CA-TCMR treatment is intensive immunosuppression that is long-acting and well-tolerated, then our strategy of combining the 4 immunosuppressive agents appeared to be a viable treatment option that might enhance immunosuppression and reduce toxicity by reducing the dosage of individual drugs. Approaches applying the same concept to pancreas transplantation alone 9 and posterior islet transplantation 10 have been reported.…”

Pancreas transplantation following total pancreatectomy for chronic pancreatitis

“…While alloislet cell transplantation has the benefit of being minimally invasive, results remain mixed with regard to longterm insulin free durability. (30) Recent reports indicate that pancreas alone transplantation following failed alloislet transplant can restore durable insulin independence even in the setting of sensitization from multiple prior alloislet infusions. (31-32) Furthermore, the incidence of total pancreatectomy continues to increase with indications for pathologies outside of chronic…”