PROTECTION OF RENAL-FUNCTION FROM ISCHEMIC-INJURY IN THE RAT

The role of cell swelling in the development of tissue injury was investigated in an ischemic model of acute renal failure in the rat. One kidney was selectively flushed with a 10% solution of polyethylene-glycol M.W. 6,000 (PEG) in normal saline prior to the clamping of the vascular pedicle, and the contralateral kidney was flushed with normal saline. Both kidneys remained ischemic for 45 min with the test solutions within their extracellular space; the concentration of PEG was chosen to prevent cell swelling during the ischemic period. After 24 h of reflow, a striking difference in function was found. The endogenous creatinine clearance in the PEG-treated kidney was 2.41±0.18 ml · min-1 Kg BW-1 {Mathematical expression}, whereas in the contralateral kidney it was reduced to 0.29±0.15 ml · min-1 Kg BW-1 (n=7, P<0.001). Microscopic examination at the end of the ischemic period revealed a widespread pattern of cell swelling in the saline-treated kidneys which was more pronounced in the inner cortex, whereas the PEG-treated kidneys were well preserved. After 24 h of reflow a comparable distribution of tubular necrosis was found in the saline-treated kidneys-again, tubular structures in the PEG-treated kidneys appeared mostly normal. These findings support the hypothesis that cell swelling is an early, important step in the development of tubular necrosis in ischemic renal injury. © 1979 Springer-Verlag.