04-2: Role of Immunosuppression and TNF-Alpha Inhibition in Outcomes of Islet-alone and Islet-after-Kidney Transplantation: Report from The Collaborative Islet Transplant Registry
06/2025
Journal Article
Authors:
Baidal, David;
Brand, Adam;
Payne, Elizabeth;
Ballou, Cassandra;
Hunsicker, Lawrence;
Alejandro, Rodolfo;
Rickels, Michael
Volume:
109
Pagination:
17
Issue:
6S1
Journal:
Transplantation
DOI:
10.1097/01.tp.0001122968.35568.eb
Keywords:
Islet transplantation alone (ITA) Islet-after-kidney (IAK) transplantation TNFα inhibition
Abstract:
Introduction: Islet transplantation alone (ITA) has been shown to result in better outcomes compared to Islet-after-kidney (IAK) transplantation. We evaluated whether immunosuppression selection and TNFα inhibition could account for differences in outcomes between ITA and IAK transplantation in 2 large cohorts from the Collaborative Islet Transplant Registry (CITR). Methods: ITA (N=984) and IAK (N=203) recipients registered in CITR with at least 1-year of follow-up, were analyzed. Mixed effects models were used to evaluate the following outcomes: C-peptide ≥0.1 nmol/L, C-peptide ≥1.0 nmol/L, HbA1c≤6.5%, insulin independence, absence of severe hypoglycemic events (SHEs), and a composite outcome of insulin independence & absence of SHE & HbA1≤6.5%. Results: In univariate analyses, HbA1c ≤6.5%, insulin independence, and the composite outcome were significantly higher in ITA vs IAK. When evaluating IS strategies in the full population and the ITA cohort, the following predictors were found to be significant for all outcomes: induction with TNFα inhibitor, maintenance with mTOR and CNI, and use of sirolimus vs MMF. In the IAK cohort, TNFα inhibition was significant for C-peptide ≥1.0 nmol/L; maintenance with mTOR and CNI was significant for absence of SHE and C-peptide ≥0.1 nmol/L; and sirolimus vs MMF was significant for all outcomes except HbA1c≤6.5%. After adjusting for confounders, differences between ITA and IAK remained for insulin independence and the composite outcome. Conclusions: Our data support the use of induction with TNFα inhibition, maintenance with combination mTOR and CNI, and the use of sirolimus over MMF as standard immunosuppression in islet transplantation. ITA outperformed IAK in insulin independence rates and the composite outcome. Further analyses aimed at identifying additional factors predictive of optimal outcomes in each of these cohorts are required.