EFFECT OF PHARMACOLOGIC AGENTS ON THE FUNCTION OF THE HYPOTHERMICALLY PRESERVED DOG KIDNEY DURING NORMOTHERMIC REPERFUSION

Abstract

We examined how a combination of pharmacologic agents ("rescue" agents) affect the function of hypothermically preserved dog kidneys at the time of reperfusion. Dog kidneys were preserved either by simple cold storage in EuroCollins'' solution for 24 or 48 hours or by continuous perfusion at 5.degree. C in Belzer''s gluconate-hydroxyethyl starch solution for as long as 5 days. After preservation, renal functions were measured with the isolated perfused kidney model. Kidneys were reperfused at normothermia either with or without the addition of a combination of rescue agents to the reperfusion medium. The rescue agents studied were allopurinol (1 mmol/L); superoxide dismutase (32,000 U/L); catalase (137,500 U/L); dimethylthiourea (3 mmol/L); glutathione (3 mmol/L); desferrioxamine (0.2 gm/L), for protection against O2 free radical injury and lipid peroxidation injury; verapamil (25 mg/L), as a Ca channel blocker; and ATP-MgCl2 (0.3 mmol/L), to stimulate energy metabolism. The renal functions we measured were glomerular filtration rate (GFR) (creatinine clearance), urine production, perfusate flow, urinary protein concentration, Na reabsorptive capacity, and tissue concentrations of ATP, K, and total tissue water. GFR was reduced by 75% to 90% after all periods of preservation, and the rescue agents had no effect on GFR. Sodium reabsorption was reduced from 98% to a range of 40% to 50% after 48 hours of cold storage or 5 days of machine perfusion and was not increased by rescue agents. There was a time-dependent increase in the amount of urine protein that was not affected by rescue agents. The addition of rescue agents did not affect total tissue water or concentrations of ATP or K in kidneys after normothermic reperfusion. These results demonstrate that pharmacologic agents previously suggested to suppress reperfusion damage in kidneys are not effective in this model. Therefore it is likely that kidney damage occurs primarily during preservation, which suggests that optimal function on reperfusion calls for the development of better methods of preservation.