Project Summary Over 700,000 people in the United States have end-stage kidney disease (ESKD). This number has increased by approximately 20,000 each year for over 2 decades. Some subgroups are more likely than others to progress from chronic kidney disease to ESKD. In addition to established racial and income disparities in chronic kidney disease progression, people engaging in high-risk substance use (i.e. with a high likelihood of health, legal, social, or financial consequences) or experiencing food insecurity or housing instability are also at increased risk. Despite their relevance in chronic kidney disease progression, we do not know the extent to which these risk factors affect patient outcomes after initiation of hemodialysis or which subgroups among patients on hemodialysis are affected by them. This is significant because patients on hemodialysis exposed to these modifiable risk factors may be particularly vulnerable to poor outcomes and high-cost healthcare utilization. The proposed study leverages the World Health Organization’s Commission on the Social Determinants of Health framework to generate two testable hypotheses: (1) High-risk substance use, food insecurity and housing instability will cluster within patient subgroups stratified by indicators of socioeconomic position; (2) this “risk factor clustering” will increase risk of hospitalization and decrease quality of life among patients on hemodialysis. Accordingly, the two specific aims of the study are to determine associations between indicators of socioeconomic position and high-risk substance use, food insecurity, and housing instability among patients on hemodialysis; and to examine the independent associations of substance use, food insecurity and housing instability with hospitalization and quality of life. The research team will enroll a convenience sample of 330 participants from the same large dialysis organization. For Aim 1, participants will complete measures of independent (age, gender, race, ethnicity, education, income and financial strain, occupation and community poverty) and dependent variables (substance use, food insecurity and housing instability), enabling cross- sectional analyses. For Aim 2, the study team will leverage a prospective cohort design to quantify associations between substance use, food insecurity, housing instability and hospitalization rate. We will follow participants for 6 months and extract hospitalization counts from dialysis facility medical records. Participants will also complete a measure of quality of life at enrollment. We will examine cross-sectional associations between substance use, food insecurity, housing instability and quality of life. The proposed study advances the National Institute of Nursing Research’s strategic goal to support self-management and improve quality of life for patients with multiple chronic conditions. Patients with ESKD self-manage highly complex treatment regimens and have multiple comorbidities. Th...