Development and validation of primary graft dysfunction predictive algorithm for lung transplant candidates

Abstract

PurposePrimary graft dysfunction (PGD) is the leading cause of early morbidity and mortality after lung transplantation. Accurate prediction of PGD risk could inform donor approaches and peri-operative care planning. We sought to develop a clinically useful, generalizable PGD prediction model to aid in transplant decision making. MethodsWe derived a predictive model in a prospective cohort study of subjects from 2012-2018, followed by a single-center external validation. We used regularized (lasso) logistic regression to evaluate the predictive ability of clinically-available PGD predictors and developed a user interface for clinical application. Using decision curve analysis (DCA), we quantified the net benefit of the model across a range of PGD risk thresholds and assessed model calibration and discrimination. ResultsThe PGD predictive model included distance from donor hospital to recipient transplant center, recipient age, predicted total lung capacity, lung allocation score (LAS), body mass index, pulmonary artery mean pressure, sex, and indication for transplant; donor age, sex, mechanism of death, and donor smoking status; and interaction terms for LAS and donor distance. The interface allows for real-time assessment of PGD risk for any donor/recipient combination. The model offers decision making net benefit in the PGD risk range of 10-75% in the derivation centers and 2-10% in the validation cohort, a range incorporating the incidence in that cohort. ConclusionWe developed a clinically useful PGD predictive algorithm across a range of PGD risk thresholds to support transplant decision making, post-transplant care, and enrich samples for PGD treatment trials.