Effect of mannitol, dextran (Macrodex®), allopurinol, and methylprednisolone on the morphology of the proximal tubule of the rat kidney made ischemic in vivo

Abstract

Rats were anesthetized and their lift kidneys were made ischemic for 1 h by clamping of the aorta just above the left renal artery. Mannitol (2.5 g/kg), Dextran 70 (0.6 g/kg), methylprednisolone (50 and 100 mg/kg), and allopurinol (100 mg/kg body weight) were administered before, during, or after the ischemia period in order to test the effect of each of these drugs upon this model of renal injury. At 24 h after the release of the aortic clamp the left kidneys of the drug treated animals wwere perfusion fixed and processed for light and electron microscopy. Dextran administration to animals with ischemic kidneys gave rise to a pronounced vacuolization ("osmotic nephrosis"), in the entire proximal tubule and especially in the pars recta. This was in contrast to dextran administration to rats with nonischemic kidenys, which showed no or very mild "osmotic nephrosis." This demonstrates that ischemia makes rat kidneys more susceptible to the development of "osmotic nephrosis." In controls (no drug treatment) one hour of renal ischemia gave partial necrosis of pars recta of the proximal tubule, while the pars convoluta tubule survived. Mannitol treatment significantly reduced the amount of necrosis of the pars recta, whereas dextran, methylprednisolone, and allopurinol had no or a negative effect on the survival of the cells of the pars recta segment. It is suggested that mannitol protects against the development of necrosis by increasing medullary blood flow in combination with a counteractive influence on the cellular swelling, which is known to occur in ischemia.