Glutathione supplementation during cold ischemia does not confer early functional advantage in renal transplantation.
BACKGROUND
Reduced glutathione (GSH), a component of University of Wisconsin (UW) solution, is reported to oxidize during storage. Consequently the commercial manufacturer of UW recommends the supplemental addition of GSH to UW before utilization. We investigated the influence of supplemental GSH during cold ischemia on early renal allograft function.


METHODS
One hundred kidneys were locally procured from heart-beating donors, preserved in our laboratory, and transplanted during an 18-month period. Selected donor, preservation, and outcome characteristics were collected and 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). During MP, perfusion characteristics (flow, resistance, perfusate electrolytes, and pH) were serially measured.


RESULTS
There were no significant differences among the groups when the donor characteristics of age, serum creatinine, and intra-operative urine output were compared. Preservation characteristics were similar among the groups with the exception of cold ischemia time, which was longer in the MP group compared to CS (26.1 h vs. 21.9 h, P=0.03). When compared with CS, kidneys 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 supplementation to perfusate resulted in no significant differences in graft outcomes.


CONCLUSIONS
Despite recommendations by the manufacturer that UW solution be routinely supplemented with GSH, supplemental GSH does not influence early renal allograft function. Our data suggest that a far greater beneficial impact on early graft function is achieved by machine perfusion. We conclude that GSH supplementation of commercially available UW is not necessary.
Department of Surgery, New York Presbyterian Hospital-Weill Medical College, Cornell University, New York, USA.
M M
MM
Polyak
B O
BO
Arrington
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S
Kapur
W T
WT
Stubenbord
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M
Kinkhabwala
D000241:Adenosine; D000328:Adult; D000493:Allopurinol; D003080:Cold Temperature; D005978:Glutathione / Q000494:pharmacology*; D006085:Graft Survival; D006801:Humans; D007328:Insulin; D007511:Ischemia / Q000503:physiopathology; D016030:Kidney Transplantation; D008875:Middle Aged; D009926:Organ Preservation; D019188:Organ Preservation Solutions; D010477:Perfusion; D011887:Raffinose; D017382:Reactive Oxygen Species; D014019:Tissue Donors; D014184:Transplantation, Homologous
D007328:Insulin; D019188:Organ Preservation Solutions; D017382:Reactive Oxygen Species; C055206:University of Wisconsin-lactobionate solution; D000493:Allopurinol; D005978:Glutathione; D000241:Adenosine; D011887:Raffinose