Background: Chronic kidney disease of non-traditional origin (CKDnt) is common among Mesoamerican sugarcane workers. Recurrent heat stress and dehydration is a leading hypothesis. Evidence indicate a key role of inflammation. Methods: Starting in sports and heat pathophysiology literature, we develop a theoretical framework of how strenuous work in heat could induce kidney inflammation. We describe the release of pro-inflammatory substances from a leaky gut and/or injured muscle, alone or in combination with tubular fructose and uric acid, aggravation by reduced renal blood flow and increased tubular metabolic demands. Then, we analyze longitudinal data from >800 sugarcane cutters followed across harvest and review the CKDnt literature to assess empirical support of the theoretical framework. Results: Inflammation (CRP elevation and fever) and hyperuricemia was tightly linked to kidney injury. Rehydrating with sugary liquids and NSAID intake increased the risk of kidney injury, whereas electrolyte solution consumption was protective. Hypokalemia and hypomagnesemia were associated with kidney injury. Discussion: Heat stress, muscle injury, reduced renal blood flow and fructose metabolism may induce kidney inflammation, the successful resolution of which may be impaired by daily repeating pro-inflammatory triggers. We outline further descriptive, experimental and intervention studies addressing the factors identified in this study.

Non‐technical summary: Brain blood flow increases during the first week of living at high altitude. We do not understand completely what causes the increase or how the factors that regulate brain blood flow are affected by the high‐altitude environment. Our results show that the balance of oxygen (O₂) and carbon dioxide (CO₂) pressures in arterial blood explains 40% of the change in brain blood flow upon arrival at high altitude (5050 m). We also show that blood vessels in the brain respond to increases and decreases in CO₂ differently at high altitude compared to sea level, and that this can affect breathing responses as well. These results help us to better understand the regulation of brain blood flow at high altitude and are also relevant to diseases that are accompanied by reductions in the pressure of oxygen in the blood.

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 influence of severe passive heat stress and hypohydration (Hypo) on cardiorespiratory and cerebrovascular function is not known. We hypothesized that 1) heating-induced hypocapnia and peripheral redistribution of cardiac output (Q̇) would compromise blood flow velocity in the middle cerebral artery (MCAv) and cerebral oxygenation; 2) Hypo would exacerbate the hyperthermic-induced hypocapnia, further decreasing MCAv; and 3) heating would reduce MCAv-CO₂ reactivity, thereby altering ventilation. Ten men, resting supine in a water-perfused suit, underwent progressive hyperthermia [0.5°C increments in core (esophageal) temperature (T_C) to +2°C] while euhydrated (Euh) or Hypo by 1.5% body mass (attained previous evening). Time-control (i.e., non-heat stressed) data were obtained on six of these subjects. Cerebral oxygenation (near-infrared spectroscopy), MCAv, end-tidal carbon dioxide (Pet_CO2) and arterial blood pressure, Q̇ (flow model), and brachial and carotid blood flows (CCA) were measured continuously each 0.5°C change in T_C. At each level, hypercapnia was achieved through 3-min administrations of 5% CO₂, and hypocapnia was achieved with controlled hyperventilation. At baseline in Hypo, heart rate, MCAv and CCA were elevated ( P < 0.05 vs. Euh). MCAv-CO₂ reactivity was unchanged in both groups at all T_C levels. Independent of hydration, hyperthermic-induced hyperventilation caused a severe drop in Pet_CO2 (−8 ± 1 mmHg/°C), which was related to lower MCAv (−15 ± 3%/°C; R² = 0.98; P < 0.001). Elevations in Q̇ were related to increases in brachial blood flow ( R² = 0.65; P < 0.01) and reductions in MCAv ( R² = 0.70; P < 0.01), reflecting peripheral distribution of Q̇. Cerebral oxygenation was maintained, presumably via enhanced O₂-extraction or regional differences in cerebral perfusion.

This is the first structured review to identify and summarize research on lifestyle choices that improve health and have the greatest potential to mitigate climate change. Two literature searches were conducted on: (1) active transport health co-benefits, and (2) dietary health co-benefits. Articles needed to quantify both greenhouse gas emissions and health or nutrition outcomes resulting from active transport or diet changes. A data extraction tool (PRISMA) was created for article selection and evaluation. A rubric was devised to assess the biases, limitations and uncertainties of included articles. For active transport 790 articles were retrieved, nine meeting the inclusion criteria. For diet 2524 articles were retrieved, 23 meeting the inclusion criteria. A total of 31 articles were reviewed and assessed using the rubric, as one article met the inclusion criteria for both active transport and diet co-benefits. Methods used to estimate the effect of diet or active transport modification vary greatly precluding meta-analysis. The scale of impact on health and greenhouse gas emissions (GHGE) outcomes depends predominately on the aggressiveness of the diet or active transport scenario modelled, versus the modelling technique. Effective mitigation policies, infrastructure that supports active transport and low GHGE food delivery, plus community engagement are integral in achieving optimal health and GHGE outcomes. Variation in culture, nutritional and health status, plus geographic density will determine which mitigation scenario(s) best suit individual communities.

An altered acid–base balance following ascent to high altitude has been well established. Such changes in pH buffering could potentially account for the observed increase in ventilatory CO₂ sensitivity at high altitude. Likewise, if [H⁺] is the main determinant of cerebrovascular tone, then an alteration in pH buffering may also enhance the cerebral blood flow (CBF) responsiveness to CO₂ (termed cerebrovascular CO₂ reactivity). However, the effect altered acid–base balance associated with high altitude ascent on cerebrovascular and ventilatory responsiveness to CO₂ remains unclear. We measured ventilation , middle cerebral artery velocity (MCAv; index of CBF) and arterial blood gases at sea level and following ascent to 5050 m in 17 healthy participants during modified hyperoxic rebreathing. At 5050 m, resting , MCAv and pH were higher (P < 0.01), while bicarbonate concentration and partial pressures of arterial O₂ and CO₂ were lower (P < 0.01) compared to sea level. Ascent to 5050 m also increased the hypercapnic MCAv CO₂ reactivity (2.9 ± 1.1 vs. 4.8 ± 1.4% mmHg⁻¹; P < 0.01) and CO₂ sensitivity (3.6 ± 2.3 vs. 5.1 ± 1.7 l min⁻¹ mmHg⁻¹; P < 0.01). Likewise, the hypocapnic MCAv CO₂ reactivity was increased at 5050 m (4.2 ± 1.0 vs. 2.0 ± 0.6% mmHg⁻¹; P < 0.01). The hypercapnic MCAv CO₂ reactivity correlated with resting pH at high altitude (R²= 0.4; P < 0.01) while the central chemoreflex threshold correlated with bicarbonate concentration (R²= 0.7; P < 0.01). These findings indicate that (1) ascent to high altitude increases the ventilatory CO₂ sensitivity and elevates the cerebrovascular responsiveness to hypercapnia and hypocapnia, and (2) alterations in cerebrovascular CO₂ reactivity and central chemoreflex may be partly attributed to an acid–base balance associated with high altitude ascent. Collectively, our findings provide new insights into the influence of high altitude on cerebrovascular function and highlight the potential role of alterations in acid–base balance in the regulation in CBF and ventilatory control.