Abstract
BackgroundIncreasing evidence suggests heat stress induced chronic kidney disease (CKD) may be mediated by endogenous fructose generation and may be exacerbated by rehydration by fructose-containing solutions. We have recently reported a model of CKD induced by heat stress. Here we test the hypothesis that rehydration with fructose may induce worse kidney injury than rehydration with equal amounts of water, and we also test if this fructose-induced injury is associated with activation of inflammasomes in the kidney.MethodsMice were recurrently exposed to heat (39.5 C0 for 30 min/h, 5 times daily for 5 wks) with rehydration consisting of 6 ml each night of water (Heat, n = 7) or fructose (Heat+F, 10%, n = 7), and were compared to control mice on water (Control, n = 7) or fructose (Fructose, n = 7). Various markers of renal injury were assessed.ResultsCompared to control animals, there was a progressive worsening of renal injury (inflammation and fibrosis) with fructose alone, heat stress alone, and heat stress with fructose rehydration (P < 0.01 by ANOVA). The combination of heat stress with rehydration with fructose was associated with increased intrarenal expression of the inflammasome markers, NLRP3 and IL-18, compared to heat stress alone. In addition, heat stress with or without fructose was associated with increased expression of caspase − 3 and monocyte chemoattractant protein-1 levels. Fructose administration was also associated with an increase in serum copeptin levels (a biomarker of vasopressin) and elevated copeptin was also observed in mice undergoing heat stress alone.ConclusionsThese studies suggest that heat stress may activate intrarenal inflammasomes leading to inflammation and renal injury, and provide evidence that rehydration with fructose may accelerate the renal injury and inflammatory response.
Highlights
Increasing evidence suggests heat stress induced chronic kidney disease (CKD) may be mediated by endogenous fructose generation and may be exacerbated by rehydration by fructose-containing solutions
We have raised the hypothesis that chronic recurrent heat stress might be able to induce chronic kidney disease (CKD), and we have hypothesized this may be of relevance to the epidemics of CKD being observed in among agricultural workers in various hot communities in Central America, India, Sri Lanka and elsewhere [15,16,17]
Experimental design The experimental study consisted of four groups (n = 7 each): Wild type (WT) control (Control); WT fructose (Fructose); WT mice exposed to heat and water restriction with water rehydration (Heat); and WT mice exposed to heat and water restriction with fructose-containing drinking water (10% fructose) as the rehydration fluid (Heat + F)
Summary
Increasing evidence suggests heat stress induced chronic kidney disease (CKD) may be mediated by endogenous fructose generation and may be exacerbated by rehydration by fructose-containing solutions. We have raised the hypothesis that chronic recurrent heat stress might be able to induce chronic kidney disease (CKD), and we have hypothesized this may be of relevance to the epidemics of CKD being observed in among agricultural workers in various hot communities in Central America, India, Sri Lanka and elsewhere [15,16,17]. To investigate this hypothesis, we developed a model of CKD induced in mice by repetitive heat stress and Milagres et al BMC Nephrology (2018) 19:180 dehydration over a 5 week period. Mice lacking fructokinase were protected from the renal injury of recurrent heat stress [18]
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