Background:

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.

Methods:

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.

Results:

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.

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.

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.

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