Introduction

Objective methods for assessing the quality of pancreata for transplantation are urgently required. Donors after brain death (DBD) experience a catecholamine storm and systemic inflammation, which may result in pancreatic damage. We hypothesized that donors requiring insulin (+IN) experience a pro-apoptotic state culminating in beta-cell death.

Methods

Plasma samples from DBDs +IN (n = 6) and -IN (n = 4) were collected at two time-points (TP): 1) at the time of consent for organ donation; and 2) 24hrs later at aortic cross clamp during organ procurement. miRNA levels, assessed by PCR, were compared between groups and TPs.

Results

miR-375 (a marker of beta-cell death) was down-regulated -2.5 fold comparing +IN vs. –IN at TP1, but up-regulated +4-fold at TP2 (p=0.027). When comparing TP2 vs. TP1, in the +IN cohort, miR-375 was unchanged between the time-points, whereas in the -IN cohort, miR-375 was down-regulated -8-fold (p=0.008).

In +IN compared to –IN donors, levels of the pro-apoptotic miR-34a showed a trend to down-regulation -12-fold (p=0.212) at TP1, but up-regulation +6-fold at TP2 (p=0.349). Similarly, miRs 26a (regulates insulin production) were up-regulated +40-fold (p=0.252) at TP1, but down-regulated -7-fold (p=0.191) at TP2 (p=0.184).

Conclusions

Greater expression of miR-375 in +IN donors compared to –IN donors suggests higher and persistent levels of beta-cell death in +IN donors. In –IN donors, a reduction in miR-375 24 hours later is in keeping with recovery from brain death related beta-cell stress. Donor insulin use may therefore be a surrogate of beta-cell death potentially predicting adverse outcomes.

CITATION INFORMATION: Shapey M., Summers A., O'Sullivan J., Yianoullou P., Augustine T., Rutter M., van Dellen D. Insulin Use on Intensive Care Units as a Marker of beta-Cell Death in Brain Dead Pancreas Donors Am J Transplant. 2017;17 (suppl 3).

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