The kidneys’ integrative responses to heat stress aid thermoregulation, cardiovascular control, and water and electrolyte regulation. Recent evidence suggests the kidneys are at increased risk of pathological events during heat stress, namely acute kidney injury (AKI), and that this risk is compounded by dehydration and exercise. This heat stress related AKI is believed to contribute to the epidemic of chronic kidney disease (CKD) occurring in occupational settings. It is estimated that AKI and CKD affect upwards of 45 million individuals in the global workforce. Water and electrolyte disturbances and AKI, both of which are representative of kidney-related pathology, are the two leading causes of hospitalizations during heat waves in older adults. Structural and physiological alterations in aging kidneys likely contribute to this increased risk. With this background, this comprehensive narrative review will provide the first aggregation of research into the integrative physiological response of the kidneys to heat stress. While the focus of this review is on the human kidneys, we will utilize both human and animal data to describe these responses to passive and exercise heat stress, and how they are altered with heat acclimation. Additionally, we will discuss recent studies that indicate an increased risk of AKI due to exercise in the heat. Lastly, we will introduce the emerging public health crisis of older adults during extreme heat events and how the aging kidneys may be more susceptible to injury during heat stress.

Occupational heat stress increases the risk of acute kidney injury (AKI) and kidney disease. This study tested the hypothesis that attenuating the magnitude of hyperthermia (i.e., increase in core temperature) and/or dehydration during prolonged physical work in the heat attenuates increases in AKI biomarkers. Thirteen healthy adults (3 women, 23 ± 2 yr) exercised for 2 h in a 39.7 ± 0.6°C, 32 ± 3% relative-humidity environmental chamber. In four trials, subjects received water to remain euhydrated ( Water), continuous upper-body cooling ( Cooling), a combination of both ( Water + Cooling), or no intervention ( Control). The magnitude of hyperthermia (increased core temperature of 1.9 ± 0.3°C; P < 0.01) and dehydration (percent loss of body mass of −2.4 ± 0.5%; P < 0.01) were greatest in the Control group. There were greater increases in the urinary biomarkers of AKI in the Control trial: albumin (increase of 13 ± 11 μg/mL; P ≤ 0.05 compared with other trials), neutrophil gelatinase-associated lipocalin (NGAL) (increase of 16 ± 14 ng/dL, P ≤ 0.05 compared with Cooling and Water + Cooling groups), and insulin-like growth factor-binding protein 7 (IGFBP7) (increase of 227 ± 190 ng/mL; P ≤ 0.05 compared with other trials). Increases in IGFBP7 in the Control trial persisted after correcting for urine production/concentration. There were no differences in the AKI biomarker tissue inhibitor of metalloproteinase 2 (TIMP-2) between trials ( P ≥ 0.11). Our findings indicate that the risk of AKI is highest with greater magnitudes of hyperthermia and dehydration during physical work in the heat. Additionally, the differential findings between IGFBP7 (preferentially secreted in proximal tubules) and TIMP-2 (distal tubules) suggest the proximal tubules as the location of potential renal injury.NEW & NOTEWORTHY We demonstrate that the risk for acute kidney injury (AKI) is higher in humans with greater magnitudes of hyperthermia and dehydration during physical work in the heat and that alleviating the hyperthermia and/or limiting dehydration equally reduce the risk of AKI. The biomarker panel employed in this study suggests the proximal tubules as the location of potential renal injury.

The endothelium plays an integral role in the development and progression of atherosclerosis. Hemodynamic forces, particularly shear stress, have a powerful influence on endothelial phenotype and function; however, there is no clear consensus on how endothelial cells sense shear. Nevertheless, multiple endothelial cell signal transduction pathways are activated when exposed to shear stress in vitro. The type of shear, laminar or oscillatory, impacts which signal transduction pathways are initiated as well as which subsequent genes are up- or down-regulated, thereby influencing endothelial phenotype and function. Recently, human studies have examined the impact of shear stress and different shear patterns at rest and during exercise on endothelial function. Current evidence supports the theory that augmented exercise-induced shear stress contributes to improved endothelial function following acute exercise and exercise training, whereas retrograde shear initiates vascular dysfunction. The purpose of this review is to examine the current theories on how endothelial cells sense shear stress, to provide an overview on shear stress-induced signal transduction pathways and subsequent gene expression, and to review the current literature pertaining to shear stress and shear patterns at rest as well as during exercise in humans and the related effects on endothelial function.

Normalization of brachial artery flow-mediated dilation (FMD) to individual shear stress area under the curve (peak FMD:SSAUC ratio) has recently been proposed as an approach to control for the large inter-subject variability in reactive hyperemia-induced shear stress; however, the adoption of this approach among researchers has been slow. The present study was designed to further examine the efficacy of FMD normalization to shear stress in reducing measurement variability.

An epidemic of chronic kidney disease (CKD) is occurring in laborers who undertake physical work in hot conditions. Rodent data indicate that heat exposure causes kidney injury, and when this injury is regularly repeated it can elicit CKD. Studies in humans demonstrate that a single bout of exercise in the heat increases biomarkers of acute kidney injury (AKI). Elevations in AKI biomarkers in this context likely reflect an increased susceptibility of the kidneys to AKI. Data largely derived from animal models indicate that the mechanism(s) by which exercise in the heat may increase the risk of AKI is multifactorial. For instance, heat-related reductions in renal blood flow may provoke heterogenous intrarenal blood flow. This can promote localized ischemia, hypoxemia and ATP depletion in renal tubular cells, which could be exacerbated by increased sodium reabsorption. Heightened fructokinase pathway activity likely exacerbates ATP depletion occurring secondary to intrarenal fructose production and hyperuricemia. Collectively, these responses can promote inflammation and oxidative stress, thereby increasing the risk of AKI. Equivalent mechanistic evidence in humans is lacking. Such an understanding could inform the development of countermeasures to safeguard the renal health of laborers who regularly engage in physical work in hot environments.