Background: Telomeres consist of multiple copies (100s to 1000s) of short (6 nucleotide) repeats at the end of all chromosomes, playing a protective role against chromosome deterioration. Telomere length shortens with every cell division in somatic cells and has a fundamental role in cell senescence. Telomere length is a potential biomarker for the ‘biological age’ of a tissue. It has been previously shown that telomere length is a marker of treatment-related mortality in hematopoietic stem cell transplantation. We investigated if telomere length may be associated with kidney allograft outcome.

Methods: Subjects, enrolled at the time of transplant, were part of a multi-center prospective study of kidney allograft recipients and donors (DeKAF Genomics). DNA was isolated from peripheral blood white blood cells, obtained with consent. Telomere length was determined in 942 recipients and 1,027 living kidney donors, using multiplex PCR (RM Cawthon, Nucleic Acid Res, 37:e21, 2009). Log transformation of telomere length was used. Chronic allograft dysfunction (CGD) was defined as a rise in serum creatinine (sCr) after 3 months post-transplant, that resulted in a biopsy. Separate cox proportional hazards models were used to investigate the association of telomere length with time to CGD, time to acute rejection, or time to graft failure, stratifying by transplant center. Both univariate analysis and multivariate analysis was done. Multivariate analysis included donor age and race (for donor analysis), or recipient age and race (for recipient analysis).

Results: As has been previously shown, there was a significant association between log transformed telomere length and donor age (p=3.8e-4) and recipient age (p=3.3e-6). Univariate analysis did not show any significant associations between telomere length, in either donor or recipient DNA, and CGD, but recipient multivariate analysis did exhibit a suggestive association (p=0.07; hazard ratio 0.63) when age at transplant and race were taken into account. There was also no association of either recipient or donor telomere length for acute rejection and graft failure.

Conclusions: We show that there may be a trend between poorer graft outcome and shorter recipient telomeres, but this was not statistically significant. Recipients with shorter telomeres may have a higher predisposition to adverse outcomes. Additional analysis will need to be done to validate these findings.

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