Physiological Changes Before Dialysis Treatments Can Potentially Mediate the Effects of Extreme Heat Events on Hospital Admission Risk

Typical thermoregulatory response to elevated temperatures among healthy individuals include reduced blood pressure and perspiration. However, individuals living with end-stage renal disease (ESRD) are susceptible to physiological fluctuations that may increase their risk of mortality. As such, the underlying mechanism for extreme heat-related hospital admissions among individuals with ESRD undergoing hemodialysis (HD) is relatively unclear. Traditional mediation analysis was used to decompose the total effect between extreme heat and hospital admissions. We hypothesize that the exposure-outcome pathway is mediated by systolic blood pressure before HD treatment (preSBP) and inter-dialytic weight gain (IDWG). This study used records from ESRD patients treated at Fresenius Kidney Care clinics from 2003 to 2012 (n= 7962). Calendar day- and location-specific temperature thresholds were calculated to identify extreme heat events (EHEs) during the study period. We fitted Cox proportional hazards models with time-dependent covariates to estimate the association between EHEs and hospitalization using varying lag structures (lag0, lag1, and lag2). We examined preSBP and IDWG as mediators using VanderWeele’s difference method for each lag structure. Extreme heat exposure for each lag structure increased the hazard risk (HR) of hospital admission after model adjustments (lag2: adjusted HR= 1.09, 95% confidence interval, 1.01- 1.19; lag1: 1.08, 0.99- 1.17; and lag0: 1.16, 1.07- 1.26). In lag1 models, preSBP and IDWG significantly (p<0.05) mediated 22.54% and 1.81% of its adjusted association, respectively, and 42.16% when both are included. In lag0 models, IDWG significantly mediated -19.10% of its adjusted association, suggesting a potential protective pathway against same-day EHE effects. This work has provided a step forward to understanding potential physiological linkages between extreme heat and hospitalization. Concomitant changes in blood pressure and IDWG may have possible antagonistic effects on extreme heat-related admission. Such findings could be critical in discerning potential interventions to minimize the impact of extreme heat among ESRD patients.