*Purpose: Approximately 1/3 of pancreas transplant fail to gain glycemic control in the first days/weeks posttransplantation, requiring exogenous insulin administration. Delayed endocrine pancreas graft function (DPGF) usually resolves but may be associated with some decrease in graft survival.

*Methods: Endocrine islets were studied with light microscopy, immunostains for insulin, glucagon, CD3, CD20,CD68 and C4d and electron microscopy (EM) in 3 patients with protracted DPGF. Findings were compared with 3 control biopsies from patiensts with optimal graft function. On EM, insulin secretory granules per µm2 of β cell surface was quantitated in all biopsies (ImageJ software). The patients were induced with Alentuzumab (n=5) and Thymoglobulin (n=1) and received triple standard immunosuppression (IS).

*Results: In contrast to controls, marked injury of β cells was noted in DPGF with preservation of α cell morphology. Electron micrograph shows β cell with cytoplasmic vacuolization and sparse Insulin secretory granules, in contrast to normal density of glucagon secretory granules in the α cell.

Severe, statistically significant loss of insulin secretory granules was uniformly observed in DPGF. See table below.

After modification-adjustment of the IS regimen, 2 patients recovered graft function (totally and partially, respectively) and the other patient was re-listed due to primary non-function.

*Conclusions: Quantifiable loss of insulin secretory granules was observed in 3 patients with DPGF. In the absence of rejection or inflammatory changes suggesting allo- or autoimmune damage, these findings point to possible metabolic/toxic mechanisms for DPGF. Better understanding of this poorly characterized entity is necessary.

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