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