Preservation of renal function by adenosine-stimulated ATP synthesis in hypothermically perfused dog kidneys

Abstract

Dog kidneys were hypothermically perfused for 1 to 5 days in the presence or absence of adenosine (5 m M). Following 1, 3, and 5 days, kidneys were reperfused at normothermia in an isolated perfusion system using a bovine serum albumin containing perfusate and renal function was determined. At the end of normothermic perfusion, kidney cortical slices were removed for biochemical analysis. Kidneys preserved in the presence of adenosine generated much higher concentrations of ATP during normothermic perfusion than kidneys preserved in the absence of adenosine at all time periods studied. In kidneys reperfused (37 °C) after 3 days of preservation, the ATP concentration averaged 9.15 μmol/ g dry wt (+adenosine) vs 4.75 μmol/g dry wt (-adenosine). After 5 days, the average was 12.65 μmol/g dry wt (+ adenosine) vs. 4.00 μmol/g dry wt (-adenosine). The tissue concentration of K − was higher in kidneys perfused in the presence of adenosine for all time periods studied. The presence of adenosine had little effect on the GFR (creatinine clearance) which was reduced by about 90% from control values at both 3 and 5 days of preservation. The primary effect of adenosine on renal function was a greater preservation of the capability of the isolated perfused kidney to reabsorb Na + from the glomerular filtrate. In the absence of adenosine Na + reabsorption was reduced from 97 to 50% whereas in the presence of adenosine was reduced to only 80% after 3 days of preservation. After 5 days of perfusion Na + reabsorption was unaffected by the presence of adenosine and the amount resorbed was only 25–30% of the amount filtered. These results suggest that the adenosine stimulated synthesis of ATP during perfusion preservation of kidneys preserved renal function for up to 3 days. After 5 days of preservation, even in the presence of high tissue concentrations of ATP. renal function is reduced. Thus, long-term kidney preservation requires not only the maintenance of energy metabolism but also preservation of other factors necessary for cell viability that have yet to be described.