Research Letter
June 24, 2024
Kidney Function Biomarkers During Extreme Heat Exposure in Young and Older Adults
Zachary J. McKenna, Whitley C. Atkins, Josh Foster, et al
JAMA. Published online June 24, 2024. doi:10.1001/jama.2024.9845
Older adults are vulnerable to heat-related morbidity and mortality.1 Kidney complications account for many of the excess hospital admissions during heat waves,1 yet studies investigating the effects of age and heat on markers of kidney function are sparse. This study investigated plasma-based markers of kidney function in young and older adults following 3-hour extreme heat exposure.
Methods
These data were obtained simultaneously with previously published findings.2 Following institutional review board approval from the University of Texas Southwestern Medical Center, participants provided written informed consent. Young (18-39 years) and older (≥65 years) participants were recruited from the Dallas-Fort Worth area; exclusion criteria (such as heart disease and chronic medical conditions) appear in Supplement 1. Data collection occurred between March 2021 and March 2023. On separate randomized days (>6 days apart) participants underwent testing in a chamber maintained at 47 °C and 15% relative humidity (dry setting) and 41 °C and 40% relative humidity (humid setting). These conditions were modeled after the 2018 Los Angeles heat wave and the 1995 Chicago heat wave, respectively. A length of 3 hours was chosen to represent the duration of peak environmental temperatures during the day.3 To mimic heat generation associated with activities of daily living, participants performed seven 5-minute bouts of light (approximately 3 metabolic equivalents of task) physical activity dispersed throughout the heat exposure (Supplement 1). Participants drank 3 mL/kg body mass of water every hour.
We collected blood after 30 minutes of semirecumbent rest at baseline, end-heating (heating stopped after end-heating sample was collected), and 2 hours post heat exposure. Blood collection at baseline and 2 hours post heat exposure was performed in a thermoneutral room. We obtained a comprehensive metabolic profile (Abbott Alinity) and analyzed cystatin C via immunoassay (R&D Systems). The primary outcome was plasma creatinine, with a clinically meaningful change identified as greater than or equal to 0.3 mg/dL.4 Cystatin C was used as a secondary outcome.5
Within each environment, we analyzed data using linear mixed-effect models with main effects of time, group, and time × group interaction. For our primary and secondary outcomes, we used 2-sided Dunnett tests to compare with baseline within a group (Prism 9.4, GraphPad). Statistical significance was set to α ≤.05.
Results
Participants included 20 young adults (21-39 years) and 18 older adults (65-76 years) (Table 1).
Dry Setting
In the dry setting, mean (SD) core temperature increased by 1.4 °C (0.3) in older adults and 0.7 °C (0.3) in young adults (Table 2). Mean (SD) body mass loss was 1.1% (0.5%) in older adults and 1.2% (0.4%) in young adults. Mean (SD) creatinine statistically significantly increased from baseline (older adults, 0.89 mg/dL [0.21]; young adults, 0.88 mg/dL [0.14]) to end-heating by 0.10 mg/dL (0.11) in older adults (P = .004) but not in young adults. Mean (SD) creatinine increased from baseline to 2 hours post heat exposure by 0.17 mg/dL (0.14) in older adults (P < .001) and 0.06 mg/dL (0.08) in young adults (P = .004). Two older adults had increases in creatinine of greater than or equal to 0.3 mg/dL at 2 hours post heat exposure. Mean (SD) cystatin C statistically significantly increased from baseline (older adults, 0.78 mg/dL [0.31]; young adults, 0.74 mg/dL [0.30]) to end-heating by 0.29 mg/L (0.36 [P = .01]) and 2 hours post heat exposure by 0.28 mg/L (.30 [P = .004]) in older adults but not in young adults.
Humid Setting
In the humid setting, mean (SD) core temperature increased by 1.1 °C (0.3) in older adults and 0.6 °C (0.3) in young adults. Mean (SD) body mass loss was 0.6% (0.4%) in older adults and 0.5% (0.3%) in young adults. Mean (SD) creatinine was not significantly different between baseline (older adults, 0.89 mg/dL [0.21]; young adults, 0.88 mg/dL [0.14]) and end-heating in older adults, but decreased by −0.05 mg/dL (0.07 [P = .008]) in young adults. Mean (SD) creatinine statistically significantly increased from baseline to 2 hours post heat exposure in older adults by 0.06 mg/dL (0.01 [P = .01]) but not in young adults. One older adult had an increase in creatinine of greater than or equal to 0.3 mg/dL at 2 hours post heat exposure. There was no time by group interaction for cystatin C (interaction P = .73).
Discussion
Older adults had increases in plasma creatinine and cystatin C after exposure to the dry setting, but there were only minor changes in young or older adults following exposure to the humid setting. Though creatinine changes were modest (<0.3 mg/dL), they occurred despite the provision of water. These findings provide limited evidence that the heightened thermal strain in older adults during extreme heat may contribute to reduced kidney function. Limitations include using plasma-based markers of kidney function, a short laboratory-based exposure, and a small number of generally healthy participants.
