497 - New Onset Diabetes after Kidney Transplantation (NODAT): Impact of Tacrolimus Cessation on Outcomes

Publication Number: 2483.497

Katie MARIE. Sullivan, Ann & Robert H. Lurie Children's Hospital of Chicago, WAUWATOSA, WI, United States; Stella Kilduff, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, United States; Carlos C. Becerril Romero, Ann & Robert H. Lurie Children's Hospital of Chicago, Shorewood, IL, United States; Debora Matossian, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, United States; Beje Thomas, MCW Froedtert, Wauwatosa, WI, United States; Priya S. Verghese, Northwestern University The Feinberg School of Medicine, Chicago, IL, United States

Background: Calcineurin inhibitors (CNIs) such as tacrolimus and cyclosporine (CSA), cornerstones of modern transplant immunosuppression, are toxic to islet cells and a potential cause of NODAT, occurring in 3-20% of recipients. The impact of converting tacrolimus to an alternate immunosuppressant (IS) to reverse NODAT has not been tested in pediatric kidney recipients on steroid avoidance versus inclusive protocols.

Objective: To test whether conversion of tacrolimus to an alternative agent is associated with resolution of NODAT (HbA1c < 6.5) and/or impaired glucose tolerance (IGT) (HbA1c < 5.7), stratified by steroid free (SF) versus inclusive (SI) protocols.

Design/Methods: Data on patient and transplant demographics and outcomes were retrospectively collected on all pediatric kidney recipients less than 21 years of age at transplant diagnosed with IGT or NODAT between 1/1/2013 and 12/31/2023 from two pediatric transplant centers. Patient outcomes were compared using descriptive statistics and stratified by whether they were on steroid avoidance/free (SF) or inclusive (SI) protocols.

Results: Of the 49 patients included, 26 and 23 were on SA and SI protocols respectively: 3 (13%) and 5 (27%) of IGT patients and 5 (36%) and 3(30%) of NODAT patients on SF and SI protocols respectively were switched from tacrolimus to an alternate IS. Tacrolimus was changed to cyclosporine in all but one patient on a SI protocol who was switched to sirolimus. Following conversion to CSA, there was normalization of the HbA1c in recipients with IGT in 100% of patients on a SF protocol but none of those on a SI protocol (p=0.082). In those with NODAT, the HbA1c normalized in 40% on a SF protocol versus 66% of patients on a SI protocol (p=0.50). Rejection post-conversion occurred within six months in 3 recipients on SF protocols (2 with IGT and 1 with NODAT), and 2 on SI protocols (both had NODAT).

Conclusion(s): Converting tacrolimus to alternate immunosuppressives can be an effective option for many patients with IGT and NODAT. In recipients on a SI protocol, A1c normalization was not observed in IGT but was in NODAT. Therefore, being on a SI protocol may increase the risk of progression to NODAT in IGT patients despite switching to CSA. On a SF protocol both IGT and NODAT patients showed normalization of A1c.For patients converted from tacrolimus, close monitoring and adjustment of other immunosuppression may be necessary to prevent rejection. Prospective, multicentre studies are necessary to assess the impact of tacrolimus avoidance in posttransplant NODAT / IGT. .

Katie Sullivan CV
Katie Sullivan CV_sept2025docx[65].pdf