From shelter to stroke: A mediation-proxy analysis of homelessness-associated stroke risk in dialysis patients

Dialysis patients face high ischemic stroke risk, only partly explained by cardiometabolic and genetic factors. Homelessness, race, and other social determinants may further elevate risk, but the pathways affecting outcomes in dialysis patients remain uncharacterized.

We conducted a retrospective cohort study using the TriNetX electronic health record network, identifying 8,821 adults with at least one homelessness code and 320,432 housed adults who initiated dialysis between 2014 - 2024 with ≥ 5 years of prior data. The primary outcome was time to first ischemic stroke within 5 years. A multivariable Cox model adjusted for age, sex, race/ethnicity, and dialysis modality estimated the total homelessness effect (HR₀). We then ran 3 hazard-attenuation models, each adding 1 composite mediator block, clinical (hypertension, diabetes, hyperlipidemia, obesity), psychosocial (nicotine dependence, depression), and social-adversity (ICD-10 Z56-Z65 codes), to calculate the percent reduction in the homelessness log-hazard. Sensitivity analyses used a composite stroke-or-death endpoint and a landmark survivor cohort excluding early deaths.

Homelessness conferred a 4.61-fold higher 5-year stroke hazard. The clinical block attenuated this hazard by 12.1%, and the psychosocial block by 15.2%. In contrast, the social-adversity block amplified the effect by 27.4%, reflecting a suppressor phenomenon from under-documented social determinants of health codes. Sensitivity checks confirmed robustness, with a stroke-or-death HR 1.35 and death-free cohort HR 4.50.

Pre-dialysis homelessness and Black race independently predict stroke risk in dialysis patients. This reaffirms the need for standardized social-needs screening, area-level deprivation measures, and advanced data-extraction methods to accurately capture social adversity and guide targeted interventions.