Telomere length of recipients and living kidney donors and chronic graft dysfunction in kidney transplants.
BACKGROUND
A biological marker that would allow clinicians to determine the length of time an allograft will remain functional after transplantation would greatly aid the ability to stratify donors by risk and to use biologically "young" allografts in young recipients, maximizing the use of this rare resource. Telomere length (TL) has been proposed to be such a marker to determine the biological age of a tissue.


METHODS
We genotyped DNA from 1805 recipients and 1038 living kidney donors for TL to determine the association of TL with acute rejection (AR), chronic graft dysfunction (CGD), and graft failure of kidney allografts. DNA was isolated from peripheral blood white blood cells and TL was measured in DNA using the multiplexed monochrome quantitative polymerase chain reaction assay.


RESULTS
As has been previously shown, we found a significant association between log-transformed TL and donor age (P=3.8×10) and recipient age (P=5.6×10). Univariate and multivariate analysis did not show any significant associations between log-transformed TL in donor or recipient DNA with AR, CGD, or graft failure, although we did observe an association between donor chronological age and CGD (P=0.018).


CONCLUSIONS
Although older allografts have been shown to be at greater risk for AR and CGD, this does not appear to be associated with shorter TL. Different markers will need to be identified to determine how biological age impacts transplant outcome, such as age-related fibrosis or tubular atrophy and tubular loss.
1 College of Pharmacy, University of Minnesota, Minneapolis, MN. 2 Division of Biostatistics, University of Minnesota, Minneapolis, MN. 3 Department of Medicine, Hennepin County Medical Center, University of Minnesota, Minneapolis, MN. 4 Minneapolis Medical Research Foundation, Minneapolis, MN. 5 Department of Laboratory Medicine and Pathology, University of Minnesota, Minnesota, MN. 6 Department of Surgery, University of Minnesota, Minneapolis, MN. 7 Address correspondence to: William S. Oetting, Ph.D., Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, MN 55455.
William S
WS
Oetting
Weihua
W
Guan
David P
DP
Schladt
Winston A
WA
Wildebush
Jennifer
J
Becker
Bharat
B
Thyagarajan
Pamala A
PA
Jacobson
Arthur J
AJ
Matas
Ajay K
AK
Israni
D000328:Adult; D000367:Age Factors; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D004247:DNA / Q000032:analysis; D051799:Delayed Graft Function / Q000235:genetics; D005260:Female; D005838:Genotype; D006084:Graft Rejection / Q000235:genetics*; D006085:Graft Survival / Q000235:genetics; D006801:Humans; D007668:Kidney / Q000503:physiopathology; D016030:Kidney Transplantation / Q000379:methods*; D007962:Leukocytes / Q000166:cytology; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D051437:Renal Insufficiency / Q000503:physiopathology / Q000628:therapy*; D012306:Risk; D016615:Telomere / Q000648:ultrastructure*
D015415:Biomarkers; D004247:DNA