Abstract
Background-The major limiting factor in Clinical Transplantation today is the shortage of cadaveric kidneys. The discard rate has been reported to be as high as 18%. Currently, there are no diagnostic tools available to accurately predict graft function pretransplant. Novel prognostic screening methodology that more accurately predicts posttransplant function could help to reduce the discard rate. In the present study we evaluated whether the restoration of synthetic functions during ex vivo near-normothermic perfusion, Exsanguinous Metabolic Support (EMS), could be used prospectively to evaluate function in human cadaveric kidneys. The blinded study involved human kidneys with varying cold ischemic times (CIT), a known mediator of damage, that ranged from 13 to 70 hours. Methods-Human kidneys (n=33) were procured following discard. Kidneys were received stored hypothermically, cannulated and transitioned to EMS warm perfusion (32°C). Perfusate samples were taken at various time points and evaluated using the Luminex xMAP to test for the cytokine/chemokine profiles. The results were categorized as Group 1 <24H and Group 2 >24H CIT. Results-From a panel of 35 cytokines/chemokines six parameters: IL-6, G-CSF, MIP-1α, MIP-1β, MCP-1, and IP-10, were significant. The concentration at 30 minutes of warm perfusion was compared to the concentrations at 9H. Group 2 kidneys with >24H CIT had significant reduction in the concentration of cytokines/chemokines that is dependent on new synthesis in comparison to Group 1 with <24H CIT. A surprising finding was that kidneys from diabetic donors with <24H of CIT had impaired restored synthetic function compared to kidneys from non-diabetic donors.Figure: No Caption available.Conclusion-Evaluating synthetic function by cytokine/chemokine analysis may represent a sensitive means of assessing cadaveric renal allografts prospectively. Prolonged CIT is known to be damaging. The blinded study results suggest that restored synthetic functions during an ex vivo warm perfusion could provide a means for evaluating grafts prospectively.
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