Abstract
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.
Highlights
The past decades’ temperature increase has coincided with the recognition of high levels of chronic kidney disease unrelated to traditional risk factors such as diabetes or hypertension among heavy laborers in disadvantaged communities around the equator [1,2,3]
We provide evidence in support of the theoretical framework using a combination of original data from two sugarcane worker cohorts, each covering two seasons: one set collected in 2014–2016 at Ingenio El Angel (IEA), El Salvador [17,96], and the other set collected in 2017–2019 at Ingenio San
Inflammation biomarkers and fever were associated with kidney injury among sugarcane cutters, an observation that could provide insight into pathogenesis of kidney damage
Summary
The past decades’ temperature increase has coincided with the recognition of high levels of chronic kidney disease unrelated to traditional risk factors such as diabetes or hypertension among heavy laborers in disadvantaged communities around the equator [1,2,3]. There is increasing evidence that strenuous physical activity generating high metabolic heat when combined with high external heat exposure is associated with a risk for decreased kidney function and injury in populations at risk of CKDnt [6,7,8]. 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. We analyze longitudinal data from >800 sugarcane cutters followed across harvest and review the CKDnt literature to assess empirical support of the theoretical framework. Discussion: Heat stress, muscle injury, reduced renal blood flow and fructose metabolism may induce kidney inflammation, the successful
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