Islet alone versus islet after kidney transplantation: metabolic outcomes and islet graft survival

Abstract

Background: Isolated islet transplantation with infusions from two to three donor pancreata and Edmonton immunosuppression consistently achieves insulin independence in patients with type 1 diabetes. The success of this protocol has been attributed to a novel combination of immunosuppressive agents and avoidance of steroids; however, the outcome of islet transplantation may differ in kidney transplant recipients who are already immunosuppressed.

Methods: We compared the metabolic outcomes and graft survival of islet transplantation in our program where nine patients underwent islet transplantation alone treated with Edmonton immunosuppression and eight patients received islet after kidney (IAK) transplants under standard kidney transplant immunosuppression often including steroids.

Results: Transplants in the IAK and islet transplantation alone setting demonstrated similar islet potency (islet equivalents/unit insulin reduction) and recipients from both groups routinely gained insulin independence, functional islet mass, and duration of graft survival, however, seemed superior in the IAK group.

Conclusions: These results suggest that better islet graft function and survival may be attained using non-Edmonton rather than Edmonton immunosuppression and can include maintenance steroid therapy.

Figure 1

Assessment of the Functional Islet Mass. Plasma insulin responses to the intravenous administration of 5g arginine at t=0 min. The incremental acute insulin response (AIR_arg) was significantly lower in the ITA group compared to the IAK (p<0.05) and control (p<0.01) groups.

Figure 2

Comparison of Islet Graft Function. Metabolic control in patients of both ITA and IAK groups was assessed by measurement of the basal and the stimulated C-peptide levels 90min after the MTT at the different time points post-transplantation.

Figure 3

Comparison of Islet Graft Survival. Islet graft survival in patients achieving insulin independence in the study groups was assessed as partial function by persistence of measurable levels of basal C-peptide (>0.5 ng/mL) and complete function with independence from exogenous insulin after islet transplantation.