Klinisch II - P23 - The role of methylprednisolone in the rescue of functional graft loss after islet rejection

M.F. Nijhoff, H. Bouwsma, J. Ringers, H.J.W. de Fijter, T.A. Rabelink, E.J.P de Koning

Chair(s): drs. Christina Krikke, chirurg, UMC Groningen

Thursday 10 march 2016

13:00 - 13:30h at Foyer

Categories: Postersessie

Parallel session: Postersessies XI - Opgesplitst in 3 tijdblokken en 3 categoriëen (klinisch, basaal, donatie)

There are currently no accurate tools for the early detection of acute islet graft rejection. The diagnosis is generally made after severe functional loss has already occurred. Methylprednisolone, rituximab and immunoglobulin have been reported as treatment, but there is a scarcity of data on the efficacy of these treatment options on islet graft outcome. Therefore we compared the outcome in recipients with acute rejection that received methylprednisolone to those who did not. Methods: 7 patients with type 1 diabetes who had received an islet transplantation and had acute allograft rejection were studied. Signs of allograft rejection included sudden hyperglycemia, lower C-peptide concentrations, increased immunological markers and precipitating events. All patients received supportive care, including optimization of medical therapy. Methylprednisolone treatment consisted of 1000mg i.v. daily for three days. Clinical data before, during and 3 months after the episode of acute rejection were obtained. Patients were also assessed for islet function using insulin independence and beta score (from 0 to 8 points): a combined measure of insulin secretion and clinical outcome.

Results:
Rejection was indicated by hyperglycemia (7/7), 74.1% lower C-peptide concentrations (7/7), preceding low exposure to immunosuppressants (4/7), preceding infection (3/7), and presence of donor-specific antibodies (3/7). No change in anti-GAD titer or PRA was present in the acute phase of rejection. Two patients received i.v. steroids within one week after their first hyperglycemia; five others did not. Patient and transplantation characteristics in both groups were similar. Before the rejection, the two patients in the treated group had a beta score of 6 and 7, with the second being insulin independent; the untreated group had a median beta score of 6 with 2 of 5 patients being insulin independent. Stimulated C-peptide levels were 1.79 ±0.87 nmol/L for the treated group and 1.50±0.74 for the untreated group. Rejection occurred 7.1 (range 2.5–16) months after transplantation. No patients retained insulin independence. Beta score dropped to a median of 1 in both groups and stimulated C-peptide decreased to 0.19±0.2 and 0.28±0.46 nmol/L in the treated and untreated group, respectively.

Conclusion:
Methylprednisolone treatment in 2 patients with acute islet allograft rejection did not restore allograft function nor did it lead to better outcomes as compared to untreated patients