Glutathione supplementation during cold ischemia does not confer early functional advantage in renal transplantation

Background. Reduced glutathione (GSH), a component of University of Wiscons in (UW) solution, is reported to oxidize during storage. Consequently the c ommercial manufacturer of UW recommends the supplemental addition of GSH to UW before utilization. We investigated the influence of supplemental GSH d uring cold ischemia on early renal allograft function. Methods. One hundred kidneys were locally procured from heart-beating donor s, preserved in our laboratory, and transplanted during an 18-month period. Selected donor, preservation, and outcome characteristics were collected a nd compared by presence of supplemental GSH and method of preservation. All kidneys were randomized to receive 3.0 mM supplemental GSH to perfusate or no supplementation (control) and were preserved by either cold storage (CS ) in UW or machine perfused (MP) in UW-machine perfusate solution (MPS). Du ring MP, perfusion characteristics (flow, resistance, perfusate electrolyte s, and pH) were serially measured. Results. There were no significant differences among the groups when the do nor characteristics of age, serum creatinine, and intra-operative urine out put were compared. Preservation characteristics were similar among the grou ps with the exception of cold ischemia time, which was longer in the MP gro up compared to CS (26.1 h vs. 21.9 h, P=0.03). When compared with CS, kidne ys preserved by MP exhibited a 33.4% increase in immediate function (93% vs . 62%, P=0.01), a corresponding 29.4% decrease in the incidence of delayed graft function (10% vs, 34%, P=0.02), and a 10% improvement in short-term ( 6-month) graft survival (98% vs. 88%, P=0.02). The addition of GSH suppleme ntation to perfusate resulted in no significant differences in graft outcom es. Conclusions. Despite recommendations by the manufacturer that UW solution b e routinely supplemented with GSH, supplemental GSH does not influence earl y renal allograft function. Our data suggest that a far greater beneficial impact on early graft function is achieved by machine perfusion, We conclud e that GSH supplementation of commercially available UW is not necessary.