Chronic interstitial nephropathy in mice induced by psychosocial stress: potentiation by caffeine

Chronic psychosocial stress in male mice produces chronic interstitial nephropathy not explained by renal vascular disease or urinary infection. Four groups of male CBA mice were studied. Group 1 and group 2 were placed in Henry-Stephens complex population cages for 5 months. Group 2 had caffeine, 800 micrograms/ml, added to their drinking water. Control groups 3 and 4 were unstressed, but group 4 had 800 micrograms/ml of caffeine added to their water. Stressed animals developed chronic interstitial nephropathy which was more severe in animals drinking caffeinated water. In addition, the percent of cortex involved in interstitial fibrosis was higher in group 2, 18.0 +/- 1.4, than in group 1, 15.2 +/- 2.3 (p less than 0.05). Both groups had more fibrosis than unstressed animals (p less than 0.01). Blood urea nitrogen was more elevated in group 2, 47 +/- 13 mg/dl, than in group 1, 29 +/- 17 mg/dl (p less than 0.05). Again both values exceeded those in unstressed animals (p less than 0.01). It is concluded that prolonged environmental stress can lead to the renal morphologic changes of chronic interstitial nephritis. Both renal pathology and function are worse when there is concurrent high caffeine intake. The relevance of this model to human disease related to analgesic use or with affective illness requires further study.