PROJECT SUMMARY / ABSTRACT Peripheral artery disease (PAD), characterized by diseased arteries to the limbs, affects 200 million people worldwide and 9 million people in the U.S. Chronic kidney disease (CKD) affects 20 million people in the U.S. and confers a markedly higher risk for PAD. Yet patients with CKD are less likely to have revascularization procedures and are more likely to undergo lower extremity amputation than patients without CKD. In addition to a high prevalence of traditional risk factors such as hypertension and diabetes mellitus, patients with CKD have other unique risk factors such as chronic inflammation or uremia, which in turn can lead to more aggressive PAD at a younger age. Therefore, patients with CKD need dedicated study. Our overarching goal is to help close these evidence gaps and address these limitations by harnessing the power of Optum Clinformatics Data Mart, which includes over 7 billion claims records on over 83 million unique lives from all 50 states spanning 2005-2019. Our secondary goal is to facilitate future PAD studies using real-world data by leveraging the power of natural language processing to improve our ability to accurately and automatically ascertain PAD from large electronic health record databases. Our innovative algorithm will be of particular importance among subgroups where clinical trial evidence is limited, such as in advanced CKD. Our proposal has the Specific Aims. Aim 1: To evaluate lower extremity revascularization in patients with non-dialysis- requiring CKD. We hypothesize that patients with CKD undergoing surgical versus endovascular revascularization will have longer initial hospitalization, but fewer subsequent major adverse limb events. AIM 2: To evaluate antiplatelet and anticoagulant medications after lower extremity revascularization in patients with non-dialysis-requiring CKD. We hypothesize that real-world patients with CKD treated with antiplatelet medications or direct oral anticoagulants after lower extremity revascularization will have higher rates of bleeding but lower rates of major adverse limb events. AIM 3: To develop an algorithm that accurately and automatically ascertains PAD from electronic health record databases. We hypothesize that a natural language processing-approach applied to diagnostic vascular testing reports will have better test performance (i.e. sensitivity, specificity, positive and negative predictive values) for identifying PAD than a traditional approach that uses administrative billing codes. Manual chart review will serve as the gold standard.