Date: Monday, May 4, 2015
Session Time: 5:30pm-6:30pm
Presentation Time: 5:30pm-6:30pm
Location: Exhibit Hall E
Pulsatile Hypothermic Machine Perfusion (MP) offers an opportunity to define inflammatory molecules generated during renal ischemia. This study reports on allografts pumped at our OPO, Lifesharing®, in which serial perfusate samples were analyzed for time-dependent generation of inflammatory mediators.
Perfusate of 17 kidneys from non high risk kidney donors was analyzed over time using Biorad Bio-plex Pro Human Cytokine and RBM Human Kidney Toxicity 1 assays® for IL-1b, IL-1Ra, IL-2, IL-4, IL-6, IL-10, IFNg, MCP-1, MIP1a, TNFa, IL-18, MCP-1, and Kim-1. Inflammatory mediators were categorized at 4 hours (as low versus high secretors) and correlated with average on-pump resistance.
Amongst inflammatory molecules, only MCP-1 demonstrated a significant time-dependent increase. IFNγ and Interleukin-6 trended to an increase, whereas all other inflammatory molecules did not increase over time.
Table 1: Generation of inflammatory mediators over time. Results are presented as pg/mg of total protein. Only cytokines that increased from time 0 (pre-pump flush) are included in the table. Errors represent SEM.
|0 hr||20 +/-1||2 +/- 0.06||90+/- 5|
|2 hr||26 +/-1||6 +/- 0||133+/- 4|
|4 hr||25+/- 1||7+/- 0||151+/- 6|
Of cytokines that increased over time, only IL-6 correlated with high vascular resistance (p=0.02).
Table 2: Mean on-pump resistive indices between lowest and highest secretors of IFNγ, IL-6, and MCP-1.
|Low Secretor||High Secretor||p-value|
|IL-6||0.20 (+/- 0.06)||0.30 (+/- 0.05)||0.005|
|IFN-γ||0.25 (+/- 0.09)||0.26 (+/- 0.08)||0.700|
|MCP-1||0.25 (+/- 0.08)||0.25 (+/- 0.08)||0.975|
Conclusions: Kidney allografts on-pump significantly released MCP-1 and trended to higher release of IFNγ and IL-6 over time, but only IL-6 secretion was correlated with high resistive indices. These data suggest MCP-1, as well as IFNγ and IL-6, may play an important trigger for post-transplant inflammation. The association of IL-6 with on-pump resistive indices suggests that IL-6 may serve as an important biomarker for high pump resistance. Our laboratory is currently evaluating the relevance of these findings to renal transplant outcomes.
To cite this abstract in AMA style:Cohen J, Ratigan E, Shigeoka A, Steiner R, Stocks L, McKay D. Inflammatory Profiling of Hypothermic Machine Pumped Kidney Allografts [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/inflammatory-profiling-of-hypothermic-machine-pumped-kidney-allografts/. Accessed April 18, 2019.
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