Impact of Angiotensin Blockade on Development of Chronic Lung Allograft Dysfunction

Abstract

Background: The renin-angiotensin-aldosterone system (RAAS) is responsible for a multitude of physiological functions, including immunological effects such as promotion of TGF-β and upregulation of IL-6 and IL-8 which are also implicated in the development of chronic lung allograft dysfunction (CLAD). Blockade of the RAAS pathway in pre-clinical models has demonstrated a decrease in these cytokines and pulmonary neutrophil recruitment. Objective: This study sought to evaluate whether use of RAAS inhibitor (RAASi) in lung transplant recipients impacted CLAD-free survival. Methods: In this retrospective, single-center study, 35 lung transplant recipients who received a RAASi post-transplant were compared to 70 lung transplant recipients not exposed to a RAASi and were followed for up to 5 years post-transplant. Results: The incidence of CLAD did not differ based on RAASi treatment (34.3% in RAASi vs 38.6%, P-value .668). This was confirmed with a multivariable Cox proportional hazards model with RAASi initiation as a time-varying covariate (RAASi hazard ratio of 1.01, P-value .986). Incidence of hyperkalemia and acute kidney injury were low in the RAASi group. Conclusions: This study demonstrated no association between post-transplant RAASi use and decreased risk of CLAD development. RAASi were also well tolerated in this patient population.