CDKN2A Expression in Pre-Implantation Kidney Biopsies is the Single, Strongest Predictive Factor for Post-Transplant Renal Function at 1 Year

Introduction: CDKN2A is a proven and validated biomarker of ageing (McGlynn LM et al, Aging Cell 2009 Feb;8(1):45-51; Koppelstaetter C et al, Aging Cell 2008 Aug;7(4):491-7) . It is responsible for inducing cell cycle arrest and as such can act as a tumour suppressor. In effect, it acts as an off switch for cell proliferation. We have demonstrated previously that CDKN2A is the most robust and the strongest predictor of post transplant renal function when compared to “Gold Standard” clinical factors such as ECD kidney status, DCD vs DBD kidneys and donor chronological age. We have sought to determine if CDKN2A is better than telomere length, the original biomarker of ageing, as predictor of post transplant renal function Methods: The Maxwell® 16 DNA purification robot kits by Promega were used for for DNA isolation and RNA was extracted using the TRIzol® technique. Real time qPCR was used for the expression of CDKN2A and to determine telomere length. Demographic and clinical data was collected prospectively in an electronic database (SERPR) and supplemented by clinical record review. Data was analysed for associations with renal function – MDRD4 eGFR and Urinary Protein/Creatinine Ratio (UPCR) using univariate and multiple linear regression analysis. Results: Univariate linear regression analysis showed that CDKN2A predicts 16.9% of eGFR (n=32, p=0.011) and 15.1% of the UPCR (n=25, p=0.031) at 1 year. ECD kidney status predicted 17.4% of eGFR (n=103, p=<0.001) but only 4.6% of the UPCR (n=85, p=0.027). Univariate linear regression between telomere length and renal function was not significant. A multivariate regression model comprising CDKN2A, ECD kidney status, donor chronological age and cold ischaemic time predicted 35.6% of the eGFR (n=31, p=0.003) and 44.4% of the UPCR (n=24, p=0.004) at 1 year. Discussion: This study confirms that measurement of CDKN2A is the strongest predictor of post transplant function when compared to current organ selection criteria. It indicates that telomere length is inferior to both CDKN2A and ECD kidney status. The model provides a valuable pre-transplant prognostic score on organ quality, allowing improved and objective patient counselling and providing the possibility for targeted intervention strategies to preserve graft function