Rehydration with fructose worsens dehydration-induced renal damage

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.

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

“…The combination of dehydration, heat and rehydration with soft drink-like fluids has been studied experimentally in mice [ 68 , 69 ] and humans [ 70 ], finding that sugary drink intake exacerbates kidney injury. Rehydration with sugary drinks could induce kidney inflammation as tubular fructose metabolism stimulates reactive oxygen species and chemokine secretion [ 71 ] along with local uric acid production [ 68 ]. Tubular uric acid, both crystalline and non-crystalline, is pro-inflammatory [ 67 ].…”

“…The RAAS is activated by electrolyte and fluid loss from sweating, reducing RBF and increasing tubular water and sodium reabsorption [ 81 ]. Vasopressin, released with RAAS activity and fructose consumption [ 68 , 69 , 70 , 82 , 83 ], reduces RBF and promotes sodium reabsorption. Increased sodium and water reabsorption increase renal energy and oxygen demand [ 84 ].…”

Fructose metabolism as a common evolutionary pathway of survival associated with climate change, food shortage and droughts

“…Fructose has been shown to activate immune responses in nonimmune cells, such as by inducing leucocyte adhesion molecules (intercellular adhesion molecule‐1, ICAM‐1), in vascular endothelial cells and by stimulating chemokine secretion (monocyte chemoattractant protein‐1, MCP‐1) and inflammasome, and oxidative stress in tubular cells . In the setting of heat stress, hydration with fructose also preferentially increases the expression of inflammasomes and interleukin‐1 beta (IL‐1β) compared to water hydration alone . Fructose has also been reported to activate immune cells in vitro, resulting in increased IL‐1β and IL‐6 secretion from dendritic cells and interferon‐γ from T cells in association with a shift towards glycolysis .…”

Restricted Water Intake and Hydration with Fructose-Containing Beverages during Infancy Predispose to Aggravate an Acute Renal Ischemic Insult in Adolescent Rats

“…Interestingly, the knockdown of fructokinase, the first step in fructose metabolism, protected from dehydration-mediated kidney injury and prevented the stimulation of vasopressin secretion despite that dehydrated mice had increased serum osmolality [ 26 ]. Moreover, rehydration with a fructose-containing beverage worsened renal damage induced by dehydration [ 27 , 28 ]. In this context, the blockade of V1a and V2 vasopressin receptors with conivaptan prevented the overactivation of aldose reductase and fructokinase and provided nephroprotection [ 25 ], an effect that later was shown to be induced by the specific blockade of V2 receptor [ 24 ].…”