Calcineurin inhibitor (CNI) use in pediatric liver and kidney transplant (Tx) patients is associated with increased risk of obesity and impaired T-regulatory (Treg) cell function. (126.19)

Abstract

Abstract CNI use can cause hyperlipidemia and new onset diabetes, and obesity may have adverse effects on allograft and patient survival, but the mechanisms are unclear. Design: We assessed if CNI or rapamycin (Rapa) use correlated with the metabolic status of children (n = 62) with stable, long-term liver (26 M, 27 F) or kidney (6 M, 3 F) allografts, and if being overweight or obese (Ow/Ob) was associated with impaired Treg phenotype or function. Results: Most patients had CNI (39) or Rapa (9) monotherapy, though 12 received CNI (8) or Rapa (4) plus MMF, Aza or steroids. 45 children had normal weight, but 7 were overweight and 10 were obese. The CNI group had more Ow/Ob patients (p=0.045) and higher BMI-for age percentile (BMI) than the Rapa group (61.7 vs. 42.9, p=0.047). CNI dose correlated with BMI (0.521, p=0.013), while Rapa use negatively correlated with BMI (-0.888, p=0.044). Also, Ow/Ob patients had reduced Treg suppressive function compared to patients with normal weight (153 vs. 100 units for autologous CD4 responders, 166 vs. 92 for standard CD4 responders, 114 vs. 43 for CD8 responders, p=0.031), and BMI was negatively correlated with CTLA-4 expression in Tregs (-0.555, p=0.011). Conclusions: CNI use is associated with being overweight or obese post-Tx, and the latter are associated with impaired Treg function and phenotype. The metabolic consequences of being overweight or obese post-Tx may include disruption of immune regulation and favor a pro-inflammatory phenotype.