Glomerular Filtration Rate Reserve During Mild Passive Heat Stress Does Not Differ Between Younger Men and Women
Authors: Freemas Jessica A. , Worley Morgan L. , Gabler Mikaela C. , Baker Tyler , Hess Hayden W. , Mcdeavitt Jovi , Johnson Blair D. , Chapman Christopher L. , Schlader Zachary J. 
Published: May 2022

Purpose

The incidence of acute kidney injury during heat waves is higher in young women compared to young men. Acute kidney injury is clinically defined as an abrupt reduction in glomerular filtration rate (GFR). The magnitude of reduction in GFR during acute kidney injury is reflective of the availability of functional nephrons. Functional nephron mass is lower in women compared to men. Therefore, women may be at a greater risk of AKI during heat waves due to a reduced ability to maintain GFR. In a heterogenous group of men and women, we have recently demonstrated that GFR reserve, which is defined as the capacity to increase GFR in response to an increase in functional demand (e.g., oral protein load), is reduced with passive heat stress. This study tested the hypothesis that GFR reserve is lower in women compared to men during passive heat stress.

Methods

Following 2 hours of passive heat stress (water perfused suit), healthy young men (n=13) and women (n=12, eumenorrheic, tested in the early follicular phase) ingested a whey protein shake (1.2 g of protein/kg of body weight) to test GFR reserve. Serum (sCr) and urinary (uCr) creatinine and urine flow rate were measured pre‐protein, and 75‐min and 150‐min post‐protein ingestion. GFR was estimated from creatinine clearance (CrCl = uCr x urine flow rate ÷ sCr). Data are presented as mean ± SD.

Results

The increase in core temperature pre‐protein (men: 0.7 ± 0.2, women: 0.8 ± 0.2°C, p=0.829) and total body fluid loss (men: ‐2.9 ± 0.7, women: ‐2.9 ± 0.8%, p=0.926) did not differ between men and women. sCr did not differ between men (pre‐protein: 1.1 ± 0.2 mg/dL) and women (pre‐protein 1.0 ± 0.1 mg/dL) at any time (p=0.097) and did not change from pre‐ following protein ingestion (p=0.107). uCr was elevated above pre‐protein levels (men: 94.4 ± 78.4, women: 40.0 ± 14.0 mg/dL) in both men and women at 75‐ and 150‐ min post‐protein (p≤0.011) but did not differ between groups at any time (p≥0.105). Urine flow rate was reduced post‐protein (p<0.001), but there were no differences between men and women (p=0.331). Pre‐protein CrCl was higher in men (130 ± 32 mL/min) versus women (89 ± 12 mL/min, p=0.005), which was maintained throughout the post‐protein period (p≤0.005). CrCl increased by 15 ± 19 mL/min from pre‐ to 150‐min post‐protein in men (p=0.022) but did not differ from pre‐protein in women (change at 150‐min post‐protein: +9 ± 21 mL/min, p=0.568). However, the peak increase in CrCl post‐protein, independent of time, did not differ between men (+19 ± 19 mL/min) and women (+11 ± 19 mL/min, p=0.193).

Conclusion

During mild passive heat stress, the magnitude of increase in CrCl following an oral protein load did not differ between young healthy men and eumenorrheic women tested in the early follicular phase of the menstrual cycle. Thus, biological sex differences in GFR reserve during heat exposure do not likely contribute to the increased risk of acute kidney injury during heat waves in young women when estrogen is at its lowest levels. Whether GFR reserve during passive heat stress is modified by the menstrual cycle phase requires further investigation.