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A fructose-enriched diet has been shown to be associated with an increase in fatty infiltration of liver, kidney, and pancreas. Our objective was to determine the concentration threshold at which a fructose-enriched diet induces damage in these organs. We hypothesized that a 20% fructose-enriched diet will induce steatosis or histopathological changes in the kidneys or pancreas. In this study, 40 Wistar male rats were randomly divided into 4 groups of 10, and each group was assigned a diet of equal quantity (15 g/rat) but of varying fructose amount. The first group (control group) was fed a standardized diet. The second and third groups were fed 10% and 20% fructose-enriched diets, respectively, whereas the fourth group was fed a high-fructose diet (30% fructose). At week 16, the 30% fructose group had the highest percentage of fat-enriched cells (10%) and a significant decrease in adiponectin as compared with week 1 (P .05). Twenty percent of this group developed interstitial fibrosis, but none presented changes in the pancreatic islet structure or fibrosis. The 10% fructose group showed the absence of perisinusoidal and interstitial fibrosis, whereas these were present in the 20% fructose group, but neither group showed significant steatosis (5%) or pancreatic damage. The results suggest that a 20% fructose-enriched diet could be considered as the threshold for inducing kidney and liver damage in the rat. Nutritional interventions to reduce fructose to less than 20% of the total energy intake should be considered to prevent metabolic risks and organ damage.