PROJECT ABSTRACT Ongoing climate change is leading to an increase in the frequency and intensity of both extreme heat events (EHEs) and wildfires, a significant source of air pollution including PM2.5 (particulate matter with aerodynamic diameter less than 2.5 microns). This trend is projected to continue into the foreseeable future despite mitigation efforts because of the changes that have already taken place. Meanwhile, the number patients with end stage kidney disease (ESKD) are expected to double by 2030 compared to 2010. Using data from three Northeastern Cities (Boston, Philadelphia, Ney York), we have previously shown that EHE exposure increases risk of hospitalization and mortality among patients with ESKD. Despite very limited geographic coverage, effect estimates varied across location, race and comorbidities, highlighting the need for a national level assessment to better understand these disparities and identify subgroups/regions that confer unusually higher risk. Others have linked exposure to air pollution with development of chronic kidney disease (CKD) as well as progression of CKD to ESKD. Building on these findings and leveraging our existing data use agreement with the Renal Research Institute (a wholly owned subsidiary of Fresenius Medical Care North America (FMCNA)), we will conduct a national level assessment of the impact of EHEs and wildfire exposures, including independently and jointly, on patients with ESKDs. To accomplish our goal, we will include all patients with ESKD receiving in-center hemodialysis treatment between 2000-2019 and 2022-2025 at approximately 2,500 dialysis clinics operated by FMCNA in our analysis. Under Aim 1, we will quantify the associations between exposure to EHEs and the risk of both hospitalization and morality using a case-crossover study design. We will further examine how this risk varies by sex, age, race/ethnicity, comorbidities, intra-dialytic hypotension (IDH), socioeconomic status (SES), neighborhood-level characteristics, and climate region. In Aim 2, we will examine the association between exposure to wildfires (wildfire smoke plumes and wildfire-related PM2.5) and risk of hospitalization and mortality in patients with ESKD and effect modification by the aforementioned variables. Under Aim 3, we will investigate the interactive effect of wildfires and EHEs in hospitalization and mortality risk among ESKD patients. With the projected increases in EHE and wildfire frequencies combined with the doubling of patients requiring kidney replacement therapy across the globe by 2030, our findings will inform management guidelines and lead to the development of early warning systems helping treatment facilities manage caseloads and enable person-centric treatment. In doing so, this proposal addresses two of the three primary areas described in AHRQ’s recent Special Emphasis Notice (NOT-HS-23-006): 1) creating resilient healthcare systems and communities that can plan, prepare, respond, and ada...