Pathophysiological Mechanisms by which Heat Stress Potentially Induces Kidney Inflammation and Chronic Kidney Disease in Sugarcane Workers

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.

Dysuria, heat stress, and muscle injury among Nicaraguan sugarcane workers at risk for Mesoamerican nephropathy

“…Scand J Work Environ Health -online first Dysuria, heat events, and muscle events in sugarcane workers Among sugarcane workers, cane cutters appear at greatest risk of MeN (6,(9)(10)(11)(12). One of the main proposed causal hypotheses has focused on the potential physical challenges faced by cane cutters, including strenuous physical exertion in extreme heat (3,(13)(14)(15)(16)(17)(18), such that volume depletion in conjunction with other factors, such as muscle injury, results in recurrent episodes of subclinical kidney injury that eventually manifest with clinically apparent CKD (13)(14)(15)(16)(17)(18)(19).…”

“…With demanding physical exertion, cane cutters may also be at risk of muscle damage with release of nephrotoxic proteins from muscle, including myoglobin (13,14,(17)(18)(19)(24)(25)(26). Elevated concentrations of muscle injury biomarkers, myoglobin and creatinine kinase (CK), are associated with muscle damage-related illness and acute kidney injury (AKI) (24)(25)(26)(27).…”

Sugarcane Workweek Study: Risk Factors for Daily Changes in Creatinine

“…Studies have shown biochemical evidence of heatinduced kidney injury. 23,24,27,59 which can be induced with increases in serum and urine uric acid and extracellular volume depletion. 53 In addition, rest breaks were found to be protective against severe increases in creatinine and a nonsignificant trend that increasing USG was associated with increases in creatinine.…”

Heat Safety in the Workplace: Modified Delphi Consensus to Establish Strategies and Resources to Protect the US Workers

“…More recently, the impact of hypohydration on aspects of worker health beyond the workplace has begun to be elucidated. For instance, repeated exposure to a hypohydrated state caused by severe physical work in the heat has been proposed to bring about chronic kidney disease, which is speculated to be due to the workers experiencing repeated bouts of subclinical kidney injury (Glaser et al., 2016 ; Hansson et al., 2020 ; Johnson et al., 2019 ; Mix et al., 2018 ; Nerbass et al., 2017 , 2019 ; X. Yang et al., 2020 ). Cases of chronic kidney disease have been reported in workers performing manual work in hot environments in hottest regions in the world (Aguilar & Madero, 2019 ; Butler‐Dawson et al., 2019 ; Glaser et al., 2016 ; X. Yang et al., 2020 ).…”