With the aging donor population, accurate assessment of tissue quality of deceased donor kidneys is required to determine the intermediate and long term graft performance, and is the major unmet need.We have previously shown that the expression of acute kidney injury transcripts (IRRAT) in implant biopsies is predictive of immediate function/delayed graft function in the first week post-transplant. In the present study we asked whether post-transplant intermediate (3 months) and late (12 month) graft function i.e. high serum creatinine could be predicted by p16/INK4a (CDKN2A) transcript, the classic somatic cell senescence marker whose expression represents the biological age/quality of an organ, compared to IRRAT expression.

We analyzed 64 implantation (1-hour) biopsies from brain dead donors. p16/INK4a expression was measured by qPCR (p16/INK4a is not assessable by microarrays) and compared to IRRAT expression measured by microarrays. Clinical risk evaluation of kidney function included KDRI, Irish and Schold scores. The intermediate/late graft function (3 and 12 months) was defined as poor with serum creatinine>132 um/L.

We compared molecular, demographic, and clinical scores in implant biopsies for their association with serum creatinine at 3 and 12 months post-transplant. Only expression of p16/INK4a was significantly associated (by p-value) with the elevated serum creatinine at 3 and 12 months (AUC of 0.71 and 0.70 for 3 and 12 months, Figure 1A).

IRRAT expression, donor and recipient age and clinical risk scores were not significantly associated with the intermediate/late graft function. IRRAT expression was only associated with early (seven day) elevated creatinine (Figure 1B). The association of p16/INK4a with the intermediate/late function was unique: global gene expression analysis by microarrays comparing implantation biopsies from kidneys with good or poor function at 3 and 12 months found no significant transcripts.

Thus defining the molecular changes at organ implantation can predict both immediate (IRRAT) and intermediate/late transplant performance (p16/INK4a), allowing a rapid qPCR test to assist clinicians with patient management.

CITATION INFORMATION: Famulski K., Halloran P. Expression of the Senescence Marker P16/INK4A in Kidney Implantation Biopsies is Uniquely Associated with Poor Late Graft Function Am J Transplant. 2017;17 (suppl 3).

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