Investigating the role of clinical measures before dialysis treatment as mediators in the association between ambient temperature and mortality/hospital admissions

Abstract

BACKGROUND AND AIM: Typical thermoregulatory responses among healthy individuals include reduced blood pressure and perspiration. Individuals living with end-stage renal disease (ESRD) are susceptible to physiological fluctuations caused by ambient temperature changes that may increase health complications. We investigated whether systolic blood pressure (preSBP) and interdialytic weight gain change (IDWG) can independently mediate the association between ambient temperature and hospital admissions and between mortality outcomes among ESRD patients. METHODS: The study population consisted of ESRD patients in Philadelphia County, PA, from 2011 to 2019 (n=1981). Within a time-to-event framework, we estimated the association between daily maximum dry-bulb temperature (TMAX) and, in separate models, all-cause hospital admissions (ACHA) and all-cause mortality (ACM) outcomes during warmer calendar months. The study employed the difference (c-c') method to decompose total effect models for ACHA and ACM using preSBP and IDWG as time-dependent mediators and then applied proportion mediated (PM) using indirect effects. Covariate adjustments for total and direct effect models include age, race/ethnicity, blood pressure medication use, treatment location, preSBP, and IDWG. RESULTS:Based on Lag 2- Lag 1 temporal ordering, 1°C TMAX increase in was associated with an increased hazard of ACHA by 7.6% (adjusted hazard ratio (HR), 1.076; 95% confidence interval, 1.070-1.082) and ACM 7.5% (adjusted HR, 1.075, 1.050-1.100). Mediation analysis for hospital admission events identified significant indirect effects for all three studied pathways and significant indirect effects for IDWG and conjoined preSBP + IDWG pathways for mortality. The mechanistic path for IDWG, independent of preSBP, demonstrated inconsistent mediation in ACHA (-2.67%) and ACM (-6.26%). PM estimates from the conjoined pathway suggest that it is likely not a candidate path in combined pathway models. CONCLUSIONS:This work has provided a step toward understanding physiological linkages that may explain or suppress temperature-driven hospital admissions and mortality risks. These findings could help discern candidate heat-adaptation interventions. KEYWORDS: Survival, temperature, Short-term exposure, Epidemiology, Mortality, Environmental epidemiology