Background

Replicative senescence is associated with telomere shortening. In native kidneys, obtained prior to transplantation, we recently described and validated a significant association between shorter intrarenal telomere length and renal arteriosclerosis. After renal transplantation, animal experiments suggested that ischemia-reperfusion injury, acute rejection episodes, and cytomegalovirus disease associate with accelerated renal allograft senescence. The association between post-transplant events and replicative senescence has not yet been evaluated in a human setting.

Methods

In a cohort of 134 kidney allograft recipients, we performed protocol-specified renal allograft biopsies at three months, one year, two years and five years after transplantation (N=579 biopsies). We used quantitative real-time PCR to measure intrarenal relative average telomere length (T/S ratio).

Results

At 5 years after transplantation, shorter intrarenal telomere length was associated with male donor gender, and older donor age, donor history of hypertension, and donor cardiovascular risk, which confirms the associations observed in native kidneys. Recipient characteristics and post-transplant events like delayed graft function, acute rejection episodes, presence of donor-specific antibodies, cytomegalovirus disease and immunosuppressive regimen did not associate with alterations of intrarenal telomere length at 5 years. Independent of donor age and donor cardiovascular risk, intrarenal arteriosclerosis in 5y protocol biopsies, and progressive arteriosclerosis over time after transplantation, associated with shorter telomere length.

Moreover, telomere attrition augments the association between older donor age and the presence of severe arteriosclerosis. In the group with the oldest donor age and shortest telomere length, there was significantly more severe arteriosclerosis (43%) in protocol biopsies at five year after transplantation, compared to other combinations. Intrarenal arteriosclerosis at 5 years after transplantation did not associate with post-transplant clinical events.

Interpretation

We demonstrate that intrarenal telomere length at 5 years after transplantation, as marker for replicative senescence, associates with renal arteriosclerosis, and reflects kidney donor characteristics, but not post-transplant events.

CITATION INFORMATION: De Vusser K, Martens D, Lerut E, Kuypers D, Nawrot T, Naesens M. Replicative Senescence and Arteriosclerosis After Kidney Transplantation. Am J Transplant. 2016;16 (suppl 3).

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