Telomere Length, Cardiovascular Risk and the Discrepancy Between Baseline and Post-Transplant Renal Allograft Histology.

Abstract

Background: The impact of senescence (biological aging) on post-transplant renal allograft histology is unknown. Methods: In blood samples from 300 deceased kidney donors, telomere length was measured. The recipients of these kidneys underwent protocol biopsies at 3, 12, 24, 36 and 60 months. Results: Both at baseline and at 3 months post-transplant, shorter donor telomere length associated significantly with cv (arteriosclerosis)(p=0.0002 and p=0.03 respectively), independent of classic cardiovascular risk factors. In contrast, and similar to what was seen in baseline biopsies, older donor calendar age associated significantly with IFTA and Gs in protocol biopsies performed at 3 months post-transplantation (p<0.0001). In addition, older donor age correlated with cv in 3-months protocol biopsies (p<0.0001). Shorter telomere length did not associate with any other histological lesion in this earliest phase post-transplant. In protocol biopsies performed later than 3 months post-transplant (at 12, 24, 36 and 60 months), older donor age associated with the same histological lesions as in the baseline biopsies (p<0.0001) but also with cv (p<0.0001) and ah (p=0.01). Interestingly, at these later time points after transplantation, shorter donor telomere length did no longer correlate with cv or other histological lesions. Telomeres were significantly shorter in biopsies with early presentation of cv in contrast to biopsies with late presentation of cv (p=0.05). Conclusion: Older donor calendar age associates with glomerulosclerosis and chronic tubulo-interstitial damage at all time points after transplantation. In contrast, donor telomere shortening, as hallmark of renal allograft biological age, correlates with intrarenal arteriosclerosis in the early months post-transplant, but not with other histological features. Later after transplantation, the impact of donor telomere shortening on graft histology decreased, likely due to other post-transplant factors that affect post-transplant histology, not related to donor kidney biological age. Whether this discrepancy can be explained by accelerated ageing associated with rejection or infectious episodes, warrants further study.