PROXIMAL TUBULAR-NECROSIS ASSOCIATED WITH MALEIC-ACID ADMINISTRATION TO THE RAT

  • 1 January 1982
    • journal article
    • research article
    • Vol. 46  (1) , 79-88
Abstract
Administration of maleic acid to the rat is used as an experimental model of [human] Fanconi''s syndrome. To determine the site and extent of morphologic injury within the kidney after maleic acid administration, renal tissue was systematically using light, transmission electron, and scanning electron microscopy. Tissue was studied either immediately or 24 h after rats received maleic acid, 200 or 400 mg/kg body wt, and was compared with tissue from controls. In kidneys of maleic acid-treated rats, evidence of injury was observed only in cells of the late pars convoluta and the pars recta in the medullary rays of the cortex and in the outer stripe of the medulla. Injured cells were characterized by an increase in cytoplasmic density, accumulation of numerous small vesicles in the apical region of the cells, abnormal-appearing mitochondria with compressed cristal membranes and flocculent densities, and focal loss of microvilli. Injury was apparent immediately after maleic acid administration and progressed to extensive necrosis by 24 h after either the 200- or 400-mg/kg dose. Except for the presence of granular and hyaline casts in the lumena, the loops of Henle and distal convoluted tubules were normal. Collecting ducts in the outer medulla, but not in the cortex, medullary rays or inner medulla, had significantly increased numbers of dark cells per total cell population when compared with controls (P < 0.005). This increase in dark cells may represent an adaptive response of the medullary collecting duct to the functional abnormalities of maleic acid-induced Fanconi''s syndrome. Collecting ducts showed no evidence of cell injury or necrosis. Apparently maleic acid, like many other renal toxins, produces tubular injury and necrosis only in proximal tubules, primarily in the medullary rays, and outer stripe of the medulla, and not in the distal tubules.