THE HISTOPATHOLOGY OF KIDNEY CHANGES IN RATS AND MONKEYS FOLLOWING INTRAVENOUS ADMINISTRATION OF MASSIVE DOSES OF FCE-26184, HUMAN BASIC FIBROBLAST GROWTH-FACTOR

Intravenous administration of human basic fibroblast growth factor up to 100 mug/kg/day to Sprague-Dawley rats caused changes in the kidneys that included enlargement, vacuolation, and karyomegaly of podocytes in glomeruli, dilatation and cast formation in tubules, thickening of the media in the lobular arteries, and hyperplasia of the epithelium o f the papilla and collecting ducts. In cynomolgus monkeys there was hy perplasia of the parietal epithelium of Bowman's capsule in the glomer uli, tubular dilatation, and minimal arteriopathy. These changes were only seen at 100 mug/kg/day. The development and eventual recovery ove r time were investigated in a sequence of sacrifices. In monkeys the f irst changes were seen after 7 days of treatment, but in rats only aft er 16 days. In both species the changes had partially resolved after 3 0 days of recovery and were considered to return to normal after 60 da ys without treatment. The morphological changes were accompanied by fu nctional alterations that included proteinuria and raised blood urea. Changes that occurred in other tissues including bone, red blood cells , adrenals, ovaries, liver, gall bladder, spleen, mesenteric lymph nod es, thymus, aorta, salivary glands, and injection site are not describ ed in this paper.