Favorable effect of CD26/DPP-4 inhibitors on postoperative outcomes after lung transplantation: A propensity-weighted analysis

Abstract

We have shown the efficacy of CD26/dipeptidyl peptidase 4 (CD26/DPP-4) inhibitors, antidiabetic agents, in allograft protection after experimental lung transplantation (LTx). We aimed to elucidate whether CD26/DPP-4 inhibitors effectively improve postoperative outcomes after clinical LTx. We retrospectively reviewed the records of patients undergoing LTx at our institution between 2010 and 2021 and extracted records of patients with diabetes mellitus (DM) at 6months post-LTx. The patient characteristics and postoperative outcomes were analyzed. We established 6months post-LTx as the landmark point for predicting overall survival (OS) and chronic lung allograft dysfunction (CLAD)-free survival. Hazard ratios were estimated by Cox regression after propensity score weighting, using CD26/DPP-4 inhibitor treatment up to 6months post-LTx as the exposure variable. We evaluated CLAD samples pathologically, including for CD26/DPP-4 immunohistochemistry. Of 102 LTx patients with DM, 29 and 73 were treated with and without CD26/DPP-4 inhibitors, respectively. Based on propensity score adjustment using standardized mortality ratio weighting, the 5-year OS rates were 77.0% and 44.3%, and the 5-year CLAD-free survival rates 77.8% and 49.1%, in patients treated with and without CD26/DPP-4 inhibitors, respectively. The hazard ratio for CD26/DPP-4 inhibitor use was 0.34 (95% confidence interval (CI) 0.14-0.82, p=0.017) for OS and 0.47 (95% CI 0.22-1.01, p=0.054) for CLAD-free survival. We detected CD26/DPP-4 expression in the CLAD grafts of patients without CD26/DPP-4 inhibitors. Analysis using propensity score weighting showed that CD26/DPP-4 inhibitors positively affected the postoperative prognosis of LTx patients with DM.