American Journal of Transplantation vol:13 issue:S5 pages:481-481
13th American Transplant Congress (ATC) location:Seattle: WA date:MAY 18-22, 2013
The histology and function of kidneys is thought to deteriorate with increasing age. Replicative senescence, associated with telomere shortening, plays an important role in this biological aging process. The relationship between cardiovascular risk factors, calendar age, telomere length and renal histology is currently unknown.
Telomere length was measured by RT-PCR in peripheral blood of 160 kidney donors who also had a baseline kidney allograft biopsy at time of transplantation, by assessment of the telomere-to-single copy gene (T/S) ratio. All baseline biopsies were rescored according to the current Banff classification. The relationship between the histological lesions, donor demographics and telomere length was evaluated.
Mean T/S ratio of telomere length was 1.1±0.53. Mean donor calendar age was 47.6±14.0, 32.1% were extended criteria donors. Telomere length in peripheral blood correlated highly significantly with donor calendar age (r=-0.3; p=0.0002), which is in concordance with previous literature. Older donor calendar age was highly significantly associated with baseline histology of interstitial fibrosis, tubular atrophy and glomerulosclerosis (all p<0.01). Although there was a significant correlation between donor calendar age and telomere length, telomere length didn’t associate with the histological appearance of the baseline biopsy. None of the other donor demographic variables (donor gender, cause of death, hypertension, history of smoking etc.) correlated with telomere length in donor peripheral blood. Donor cardiovascular risk factors associated significantly with arteriolar hyalinosis and vascular intimal thickening, but did neither associate with donor calendar age nor with telomere length. This dichotomy between calendar-age associated renal histological lesions and cardiovascular risk-associated lesions was confirmed by principal component analysis on a larger cohort of 548 baseline biopsies.
Calendar age and cardiovascular risk determine renal histological damage, but biological aging and telomere shortening don’t associate with histological damage of renal tissue. The current study suggests that biological aging in itself does not lead to alterations in renal histology. Additional studies that evaluate the senescent phenotype (microarray gene expression and immunohistochemistry) of baseline biopsies are underway to investigate this unexpected finding.