Telomere Length Impacts on Allograft Function Post Kidney Transplant

Gingell-Littlejohn, M., McGuinness, D., McGlynn, L. M., Kingsmore, D., Clancy, M. J., Koppelstaetter, C., Mayer, G. and Shiels, P.G. (2011) Telomere Length Impacts on Allograft Function Post Kidney Transplant. In: 2011 American Transplant Conference, Phildadelphia, PA, USA, 30 Apr - 4 May 2011,

Abstract

Allograft biological age, as defi ned by CDKN2A expression, has recently been demonstrated to be a superior pre-transplant predictive marker for post-transplant function. Traditionally however, bio-ageing has been assessed through a measurement of telomere length. With age and increased environmental stress, telomere length is shortened which in turn may be adversely related to donor organ function. We measured renal pre-implantation telomere length and determined associations with organ function at six months post-transplant with a view to using it as a further bio-marker in kidney transplantation, which may be used in combination with CDKN2A and donor chronological age.MethodsDNA was extracted from time zero biopsies (n=32) using a Maxwell®16 DNA purifi cation robot and quantifi ed using a Nanodrop apparatus. Telomere length determination was by Q-PCR. Telomere length was then analysed with respect to donor age and sex, cold ischaemic time, delayed graft function and renal function 6 months post-transplant as determined by serum creatinine (SC) levels.ResultsDonor telomere length was observed to shorten as a function of increasing chronological age (p=0.018). No signifi cant difference was observed with respect to sex of the allograft, cold ischaemic time and frequency of delayed graft function. We did however, observe signifi cantly inferior renal function, in those who received organs with shorter telomere lengths (p=0.025) at six months post-operatively. Linear regression analysis indicated that at 6 months post-transplant, donor age explains 12.0% of the variability in SC levels, while telomere length accounted for 7.9%.ConclusionsThis study confi rms that measurement of donor bio-age pre-transplant can predict post-transplant function. It indicates that telomere length is inferior to donor chronological age when it is used as a bio-marker. This is in keeping with previous observations indicating that CDKN2A is a superior bio-marker. Telomere length in addition to donor age and other promising bio-markers of ageing may provide a valuable pre-transplant prognostic score on organ quality, allowing for targeted intervention strategies to preserve graft function.

• Item Type: Conference Proceedings
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: McGlynn, Dr Liane and Clancy, Mr Marc and Shiels, Professor Paul and Kingsmore, Prof David and McGuinness, Dr Dagmara
• Authors: Gingell-Littlejohn, M., McGuinness, D., McGlynn, L. M., Kingsmore, D., Clancy, M. J., Koppelstaetter, C., Mayer, G., and Shiels, P.G.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences; College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing