Diet and kidney diseases in rats.

Diet-associated kidney diseases of rats includes nephropathy in both sexes and nephrocalcinosis in females. High protein content of diets appears to be the major cause for severe nephropathy and changing the source of protein to one such as soy protein, restricting caloric intake, or modifying the diet to decrease protein consumption could decrease the severity of nephropathy. The NTP-2000 diet with lower protein content than most diets decreases the severity of nephropathy and increases the survival of Fischer 344 rats without substantial changes in growth patterns and body weights. Nephrocalcinosis, characterized by mineralization of renal tubules at the corticomedullary junction, has been reported in young and adult female rats of most strains and stocks suggesting a major contribution of female sex hormones to the development of this lesion. Calcium (Ca), phosphorous (P), magnesium (Mg), and chloride (Cl) imbalances, especially a Ca:P ratio of less than 1.0 in diet, are considered to be associated with this lesion. Most commercial diets commonly used for toxicology studies have a Ca:P molar ratio of less than 1.0. Increasing the Ca:P molar ratio to more than 1.0 and closer to 1.3 in the AIN-93 purified diet and NTP-2000 nonpurified diet prevents the development of this lesion. Genetics will predispose rats to some diseases and environmental factors will influence the severity of these diseases. Diet is one of the most important environmental factors. Diets balanced for nutrients without excesses could markedly improve the health of rats used in chronic studies leading to substantial increases in survival and thereby accomplish the objective of chronic toxicity and carcinogenicity studies.