Severe cyclical dehydration induces chronic renal injury in rodents. This effect is attenuated by global fructokinase deficiency, suggesting possible roles for fructokinase and fructose metabolism in mediating or promoting dehydration-induced injury. Clinical and pathological similarities between this injury model and endemic Mesoamerican nephropathy (MeN) have fueled speculation that dehydration-induced injury and MeN may share common mechanistic underpinnings involving fructokinase that can be targeted to mitigate disease development, progression, and/or severity.