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.

Personalized hydration strategies play a key role in optimizing the performance and safety of athletes during sporting activities. Clinicians should be aware of the many physiological, behavioral, logistical and psychological issues that determine both the athlete’s fluid needs during sport and his/her opportunity to address them; these are often specific to the environment, the event and the individual athlete. In this paper we address the major considerations for assessing hydration status in athletes and practical solutions to overcome obstacles of a given sport. Based on these solutions, practitioners can better advise athletes to develop practices that optimize hydration for their sports.

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.

Occupational heat exposure is linked to the development of kidney injury and disease in individuals who frequently perform physically demanding work in the heat. For instance, in Central America, an epidemic of chronic kidney disease of nontraditional origin (CKDnt) is occurring among manual laborers, whereas potentially related epidemics have emerged in India and Sri Lanka. There is growing concern that workers in the United States suffer with CKDnt, but reports are limited. One of the leading hypotheses is that repetitive kidney injury caused by physical work in the heat can progress to CKDnt. Whether heat stress is the primary causal agent or accelerates existing underlying pathology remains contested. However, the current evidence supports that heat stress induces tubular kidney injury, which is worsened by higher core temperatures, dehydration, longer work durations, muscle damaging exercise, and consumption of beverages containing high levels of fructose. The purpose of this narrative review is to identify occupations that may place US workers at greater risk of kidney injury and CKDnt. Specifically, we reviewed the scientific literature to characterize the demographics, environmental conditions, physiological strain (i.e., core temperature increase, dehydration, heart rate), and work durations in sectors typically experiencing occupational heat exposure, including farming, wildland firefighting, landscaping, and utilities. Overall, the surprisingly limited available evidence characterizing occupational heat exposure in US workers supports the need for future investigations to understand this risk of CKDnt.

The purpose of this study was to test the hypothesis that consuming a soft drink (i.e., a high fructose, caffeinated beverage) during and following exercise in the heat elevates biomarkers of acute kidney injury (AKI) in humans. Twelve healthy adults drank 2 L of an assigned beverage during 4 h of exercise in the heat (35.1 ± 0.1°C, 61 ± 5% relative humidity) in counterbalanced soft drink (Soft Drink) and water (Water) trials, and ≥1 L of the same beverage after leaving the laboratory. Stage 1 AKI (i.e., increased serum creatinine ≥0.3 mg/dL) was detected at post-exercise in 75% of participants in the Soft Drink trial compared to 8% in Water (P=0.02). Furthermore, urinary neutrophil gelatinase-associated lipocalin (NGAL), a biomarker of AKI, was higher during an overnight collection period after the Soft Drink trial compared to Water in both absolute concentration (6 ± 4 ng/dL vs. 5 ± 4 ng/dL, P<0.04) and after correcting for urine flow rate (6 ± 7 [ng×dL^-1]/[mL×min^-1] vs. 4 ± 4 [ng×dL^-1]/[mL×min^-1], P=0.03). Changes in serum uric acid from pre-exercise were greater in the Soft Drink trial than Water at post-exercise (P<0.01) and 24 h (P=0.05). There were greater increases from pre-exercise in serum copeptin, a stable marker of vasopressin, at post-exercise in the Soft Drink trial (P<0.02) than Water. These findings indicate that consuming a soft drink during and following exercise in the heat induces AKI, likely via vasopressin mediated mechanisms.