• Tamara Milagres, Fernando E García-Arroyo, Miguel A Lanaspa, Gabriela Garcia, Takuji Ishimoto, Ana Andres-Hernando, Masanari Kuwabara, Thomas Jensen, Yuka Sato, Jason Glaser, Laura G Sánchez-Lozada, Richard J Johnson, and Carlos Roncal-Jimenez.
• Division of Renal Diseases and Hypertension, Nephrology Division, Mail Stop C281, University of Colorado Anschutz Medical Campus, 12700 East 19th Ave 7th Floor Offices, Aurora, CO, 80045, USA.
• Bmc Nephrol. 2018 Jul 13; 19 (1): 180.

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.

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