Perioperative Diabetes Mellitus and Chronic Lung Allograft Dysfunction After Lung Transplantation

Abstract

<h3>Purpose</h3> Identifying the risks for chronic lung allograft dysfunction (CLAD) after a lung transplant (LTx) is beneficial to the patient. In our clinical and preclinical investigation, we showed that CD26 is expressed in CLAD-developing lung allografts, and a CD26/DPP-4 inhibitor, a glycemic agent, effectively works in post-LTx graft protection. In other words, DM and CLAD share a common characteristic as a target of the DPP-4 inhibitor. Therefore, we hypothesized that diabetes mellitus (DM) is relevant to CLAD. Our study aimed to clarify if DM is a risk for post-LTx outcome. <h3>Methods</h3> The records of patients receiving an initial LTx in our institution between 2010-2018 were reviewed retrospectively. Patient characteristics and postoperative outcomes were analyzed. We established 6 months post-LTx as the landmark point for predicting overall survival (OS) and CLAD development. To identify perioperative DM, the patient was evaluated for DM at 6 months post-LTx. Cox regression analysis was used for the landmark analysis at 6 months post-LTx for OS and CLAD-free survival. <h3>Results</h3> A total of 172 patients were investigated. DM and CLAD occurred in 76 and 40 patients, respectively, and 40 died. The five-year OS rate of the cohort was 74.4%, while the five-year CLAD-free survival rates was 62.6%. At 6 months post-LTx, the unadjusted and adjusted hazard ratios (HRs) of DM for OS were 3.46 (95% confidence interval [CI_95%] = [1.44-8.32]) and 2.78 (CI_95%= [1.39-5.56]), respectively. Unadjusted and adjusted HRs of DM for CLAD-free survival were 2.28 (CI_95%= [1.21-4.30]) and 2.05 (CI_95%= [1.09-4.02]). A Kaplan-Meier curve with the patients stratified according to presence or absence of DM shows five-year CLAD-free survival rates of 50.1% and 72.9%, respectively (Figure). <h3>Conclusion</h3> Perioperative DM was identified as an independent adverse factor for OS and CLAD-free survival. The perioperative management of DM should be considered important in the clinical field of lung transplantation.