Glomerular filtration rate reserve is reduced during mild passive heat stress in healthy young adults

Abstract

We tested the hypothesis that, compared with normothermia, the increase in glomerular filtration rate (GFR) after an oral protein load (defined as the GFR reserve) is attenuated during moderate passive heat stress in young healthy adults. Sixteen participants (5 women; 26 ± 2 yr) completed two experimental visits, heat stress or a normothermic time-control, assigned in a block-randomized crossover design. During the heat stress trial, core temperature was increased by 0.6°C in the first hour before commencing a 2-min cold pressor test (CPT) to assess renal vasoconstrictor responses. One-hour post-CPT, subjects ingested a whey protein shake (1.2 g of protein/kg body wt), and measurements were taken pre-, 75, and 150 min postprotein. Segmental artery vascular resistance was calculated as the quotient of Doppler ultrasound-derived segmental artery blood velocity and mean arterial pressure and provided an estimate of renal vascular tone. GFR was estimated from creatinine clearance. The increase in segmental artery vascular resistance during the CPT was attenuated during heat stress (end CPT: 5.6 ± 0.9 vs. 4.7 ± 1.1 mmHg/cm/s, P = 0.024). However, the reduction in segmental artery vascular resistance in response to an oral protein load did not differ between heat stress (at 150 min: 1.9 ± 0.4 mmHg/cm/s) and normothermia (at 150 min: 1.8 ± 0.5 mmHg/cm/s; P = 0.979). The peak increase in creatinine clearance postprotein, independent of time, was attenuated during heat stress (+26 ± 19 vs. +16 ± 20 mL/min, P = 0.013, n = 13). GFR reserve is diminished by mild passive heat stress. Moreover, renal vasoconstrictor responses are attenuated by mild passive heat stress, but renal vasodilator responses are maintained.

Keywords: glomerular filtration rate; heat stress; kidney function; oral protein loading; renal blood flow.

Figure 1.

Schematic of the study protocol. Participants were instrumented and underwent 20 min of normothermic baseline in both trials. Renal ultrasound measurements (indicated by transducer symbols) were taken at baseline along with blood (indicated by the syringe) and urine (indicated by collection cup). Participants were then either passively heated or remained in normothermic conditions postbaseline measures. Renal ultrasound measurements were then taken after 1 h into each experimental condition at pre-CPT and during the cold pressor test. Forty-five minutes later, preprotein ultrasound measures were collected along with the collection of blood and urine samples. Participants then ingested 1.2 g/kg of whey protein. Renal ultrasound measures were collected 75 min and 150 min postprotein along with the collection of blood and urine samples. CPT, cold pressor test.

Figure 2.

Mean arterial pressure (A), renal segmental artery blood velocity (B), and renal segmental artery vascular resistance pre-CPT (C), and every minute during the cold pressor test. Data are presented as means ± SD and individual values (normothermia: blue lines; heat stress: red lines). *Significantly different from heat stress (P < 0.046). ^PSignificantly different from pre-CPT (i.e., time = 0 min; P ≤ 0.031). Data were analyzed using a two-way linear mixed model. When a significant main effect or interaction was identified, Sidak pairwise comparisons were carried out. P values from the two-way linear mixed model are reported alongside pairwise comparisons (where necessary). n = 16 for all except for during heat stress and the segmental artery vascular resistance variable where n = 15 due to the identification of an outlier. Linear mixed model output with outlier included—time: P < 0.001, trial: P = 0.1535, trial × time: P = 0.214. CPT, cold pressor test.

Figure 3.

Segmental artery blood velocity (A), segmental artery vascular resistance (B), renal artery blood velocity (C), and renal artery vascular resistance preprotein (D), 75 min postprotein and 150 min postprotein. Data are presented as means ± SD and individual values (normothermia: blue lines; heat stress: red lines). ^PSignificantly different from preprotein (P ≤ 0.027). Data were analyzed using a two-way linear mixed model. When a significant main effect or interaction was identified, Sidak pairwise comparisons were carried out. P values from the two-way linear mixed model are reported alongside pairwise comparisons (where necessary). Normothermia: n = 16; heat stress: n = 15.

Figure 4.

Creatinine clearance preprotein, 75 min postprotein and 150 min postprotein (normothermia: n = 15; heat stress: n = 13; A), and peak change (Δ) in creatinine clearance (n = 13 paired samples; B). Data are presented as means ± SD and/or individual values (normothermia: blue lines; heat stress: red lines). ^PSignificantly different from preprotein (P = 0.043). Absolute data were analyzed using a two-way linear mixed model with Sidak post hoc comparisons. P values from the two-way linear mixed model and post hoc comparisons are reported. Peak changes in creatinine clearance were analyzed via a one tailed t test with potential outlier included and excluded.