The cause of these changes is unclear. Kidney stone formation is usually due to genetic and environmental factors. Although genetic

factors influence stone risk, changes in the gene pool occur at a slow rate. Therefore, it is PLK inhibitor unlikely to be the driving force for these trends. Environmental factors are also varied and complex, but their influence is more apparent as changes in these factors occur over much Inhibitors,research,lifescience,medical shorter intervals. We believe that changes in 2 of the most important environmental factors-diet and climate-have the most significant impact on these trends. There is historical evidence of the influence of diet on stone formation. The first documented increase in stone disease occurred during

the 16th century when European Stein-Schneiders (stone cutters) found that their services were Inhibitors,research,lifescience,medical more in demand.32 During this period, there were improvements in food production and corn became a popular food staple.33 The increased consumption of starchy foods derived from corn promoted obesity, currently a known risk factor for stone formation.3,5,34 The impact of agricultural modernization remains today, and is reflected by the epidemic in obesity seen in many countries, especially the United States. The prevalence of obesity has been tracked in the United States since 1960. Obesity in adults has risen from 14.6% in the 1971 through 1974 time period to 35.2% in Inhibitors,research,lifescience,medical the 2005 through 2006 time period.35 Moreover, a similar trend is present for children, with 11% to 17.8% being in the overweight category in the 2005 through 2006 Inhibitors,research,lifescience,medical time period.35 The consumption of fast foods and high fructose corn syrup preparations has been thought to promote this epidemic. In the United States Inhibitors,research,lifescience,medical alone, the percentage of meals coming from fast-food eateries or restaurants rose from 9.6% to 23.5% during the timeframe of 1977 to 1996.36 These dietary changes have also been reported in many other countries including China, India, Egypt, Russia, and the Philippines. 36–39 High fructose consumption has been demonstrated to be a risk Behavioral and Brain Sciences factor for stone formation.40

Other dietary risk factors for stone formation have been identified. There is strong evidence that diminished fluid and calcium consumption are risk factors.14,41–44 Increased oxalate consumption has also been demonstrated to promote stone formation. 45,46 Epidemiologic studies have demonstrated that increased sodium and animal protein intake have an equivocal impact on stone risk. However, a randomized prospective dietary intervention study demonstrated that reduction of sodium and animal protein and maintenance of normal dietary calcium intake attenuates stone activity in recurrent hypercalciuric stone formers.41 There is evidence that the consumption of animal protein has increased in a number of countries, paralleling the acceleration of stone disease.