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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 vehicle suspension (control), mefenamic acid, mefenamic acid+caffeine or caffeine only for 4 months. Renal tissue taken from the corticomedullary junction was processed for electron microscopy. Ultrathin sections were cut after identification of vasa rectae on survey sections. On subsequent morphometric analysis, percentage interstitial tissue was calculated from the total area of vasa recta less the non-interstitial tissue. The median percentage 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 less than 0.01), 29 (15-42; n = 15) in caffeine only (P less than 0.001) and 32 (20-46; n = 18) in vehicle-treated animals (P less than 0.001). There were no significant differences between mefenamic acid alone and vehicle or caffeine-only groups or between caffeine-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 interstitial tissue between adjacent afferent and efferent vasa recta.

These studies evaluate the susceptibility of the Syrian hamster to the induction of renal papillary lesions after exposure to 2-bromethylamine (2-BEA), mefenamic acid, indomethacin, acetaminophen and phenylbutazone. In most cases there were 25 animals per dose group. Papillary necrosis was produced by single or multiple ip doses of 75 mg 2-BEA/kg and above, and was present within 12 hr of administration of a dose of 500 mg/kg body weight. There were lesions in the renal papilla of hamsters 10 days after a single dose of 500 mg 2-BEA/kg. The severity of papillary lesions increased up to 4 days after exposure in hamsters given a single dose of either 250 or 500 mg 2-BEA/kg. The severity of papillary lesions did not increase with the number of doses in hamsters given multiple doses (2-5) of 100 mg 2-BEA/kg. Renal papillary necrosis was observed in about 40% of hamsters given 100, 200 or 400 mg mefenamic acid/kg. Only a few of the hamsters given indomethacin had renal papillary lesions and none of those given acetaminophen (up to 400 mg/kg) or phenylbutazone (up to 600 mg/kg) developed renal papillary lesions.