Caffeine potentiation of mefenamic acid-induced lesions in the rat renal medulla

The effect of caffeine given in combination with mefenamic acid on the renal medulla was examined. Sprague‐Dawley rats were divided into four groups and gavage fed either suspension (control), mefenamic acid. mefenamic acid + caffeine or caffeine onlu for 4 months. Renal tissue taken from the corticomedullary junction was processed for electron microscopy. Ultrathin sections were cut after identification of vast rectae on survey sections. On subsequent morphometric analysis. percentage interstitial tissue was calculated from the total area of vasa recta less the noninterstitial tissue. The median prcentage of interstitial tissue in the mefenamic acid and caffeine group was 41 (range 33–50; n = 15) compared with 34 (20–48); n = 20 in mefenamic acid (P < 0.01), 29 (15–42; n = 15) in caffeine only (P < 0.001) and 32 (20–46; n = 18) in vehicle‐treated animals (P < 0.001). There were no significant differences between mefenamic acid alone and vehicle or caffeine‐only gruops or between caffeins‐only and vehicle‐treated controls. This suggests that caffeine potentiates the effect of the non‐steroidal anti‐inflammatory drug. mefenamic acid, on the rat renal medulla, resulting in a quantitative increase in the intersitial tissue between adjacent afferent and efferent vasa recta.