Experimental acute renal failure in primates. Clinical and histopathologic evaluation in light and electron microscopy.

Acute renal failure or its equivalent, acute tubular necrosis, was induced in rhesus monkeys by a combination of dehydration, hemorrhagic hypovolemia, and packed cell transfusion. Clinicopathologic changes were studied at different time intervals. Increasing edematous swelling and disintegration of the epithelial cells in the convoluted tubules, thick loops of Henle, and collecting tubules during the first four hours were conspicuous. As a result, intratubular cellular detritus, red blood cells, and various types of casts were increased progressively between one and four hours, and decreased thereafter. As the time progressed, edema was subsiding but the absorption granules and fat droplets were increased in size and number from one to twenty-four hours. These findings would indicate widespread cellular degeneration and necrosis. Consequently, tubular integrity was impaired leading to necrosis, denuded tubular basement membranes, and occasional tubulorrhexis. Concurrently, some dilated peritubular or interstitial capillaries were ruptured releasing red blood cells and cellular debris, which eventually were picked up by the damaged tubules. Although the regeneration of the renal parenchyma was in progress after sixteen hours, groups of subcapsular tubules were dilated showing flattened epithelial cells. The glomerular capillaries were either dilated or engorged, empty or collapsed during the experiment. Bowman's spaces contained red blood cells and varying amounts of cellular debris. Although the clinicopathologic changes reported here may be attributed to one or more of the following factors, hypoxia, toxic effects and dehydration, most of the changes were apparently due to hypoxia.