An experimental evaluation of nucleotide enhancement techniques for kidney transplantation

The effect of various nucleotide-enhancing agents on renal function and intracellular nucleotide levels was evaluated in a canine autotransplant model. Thirty-five dogs (18-28 kg) underwent left nephrectomy and 30 min of warm ischemia followed by Collins C-4 flush and 24 hr of cold-storage preservation. Heterotopic autotransplantation and immediate contralateral nephrectomy was then performed. Seven equal groups were evaluated: group A--controls, group B--adenosine pretreatment (1.0 g), group C--dipyridamole pretreatment (10 mg), group D--adenosine (1.0 g), and dipyridamole (10 mg) pretreatment, group E--adenosine (200 mg) and EHNA (2.5 mg/kg) pretreatment, group F--adenosine (200 mg) and EHNA (2.5 mg/kg) in the Collins C-4 flush, and group G--adenosine (200 mg) and EHNA (2.5 mg/kg) at the time of autotransplantation. All kidneys underwent cortical biopsies at the end of preservation and 1 hr after restoration of blood flow for determinations of AMP, ADP, and ATP. In the pretreatment groups (groups B through E) there was 60% graft survival whereas the controls (group A) and the groups treated after ischemia (groups F and G) had 0, 0, and 20% graft survival, respectively. In groups B and E, ATP levels were greater than controls after preservation and 1 hr after restoration of blood flow. Group C AMP and ADP levels and group D energy charge were greater than controls in the post-transplantation biopsies. Administration of adenosine and EHNA after ischemia was not associated with increased intracellular nucleotide levels. One hour post-transplantation biopsies demonstrated greater ability to regenerate cortical nucleotides in the surviving animals but no absolute value could be identified as a predictor of viability. In conclusion, pretreatment with adenosine, dipyridamole, and EHNA alone and in combination is beneficial in ischemically injured kidneys undergoing cold-storage preservation.