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Patients who undergo kidney transplantation have improved survival and lower cardiovascular
risk relative to wait-listed dialysis patients. This suggests that transplant may
positively impact cardiovascular risk. Though this effect likely occurs through several
processes, here we examined the effect of kidney transplantation on arterial stiffness
by assessing PWV. In this prospective study of 66 new kidney transplant recipients,
we showed that there was no change in aortic PWV over the first year post kidney transplant,
suggesting arterial stiffness does not progress during this time period. Increasing
age, having diabetes and higher baseline PWV score were associated with increased
PWV score at 12 months and may help identify patients with increased arterial stiffness.

Previous studies have suggested that PWV progresses with time on dialysis. For example,
Utescu and colleagues showed an annual increase of 0.84 m/s per year (95 % CI 0.50?1.12 m/s
per year) in a cohort of 109 hemodialysis patients 12]. In another study of 88 wait-listed patients in which 39 were transplanted and 49
were not, during one year follow up no difference was seen in PWV between the 2 groups,
though follow up time for those transplanted was short (median 6.3 months) 17]. In our study, in contrast to dialysis patients, we did not see PWV progression over
the first year post transplant. One interpretation could be that restoration of kidney
function with transplant has a positive impact on slowing the process of arterial
stiffness. However, further study is needed to see if this trend continues over longer
time periods, and more importantly if this is associated with decreased CVD events.
Given the adverse metabolic effects of routinely used immunosuppression drugs, it
is possible that with more time the balance shifts the opposite direction.

For kidney transplant recipients, prior cross-sectional studies have shown that transplant
recipients have higher aortic PWV measurements than historical healthy controls. The
reported median normal values for a large European population of individuals aged
40–49 was 6.9 m/s and aged 50–59 was 8.1 m/s compared to 9.25 m/s in our patient cohort
with a median age of 49.7 years 9]. In a retrospective study, 106 patients in Lebanon at a mean 54.1 months post transplant
had mean aortic PWV of 11.1?±?2.8 m/s compared to 8.7?±?1.6 m/s in a previously studied
healthy male cohort. The mean PWV value in that study was much higher than what we
observed in our cohort. In addition, the transplant recipients who had experienced
more cardiovascular events at time of PWV assessment had a significantly higher aortic
PWV than those who did not (12.8?±?4.3 vs 10.9?±?2.5 m/s, respectively, p??0.05)
18]. Similarly a study from Belgium of primarily white patients showed a higher baseline
measure of PWV was associated with more cardiovascular events after a mean follow
up of 5 years (11.2 vs 9.2 m/s, p??0.001) 19].

These prior studies had single time points of PWV assessments of prevalent transplant
recipients, with patients enrolled at varying times post transplantation. Our study
was different in that it followed incident patients from time of transplant, with
measurements at baseline and one year, adding further information about what happens
to PWV over time. Our results indicate that changes in aortic stiffness may be slowed
with successful transplantation, consistent with two previous smaller studies over
a shorter time period of 3 months 20], 21]. In the study by Ignace, et al. aortic stiffness changes post transplantation were
dependent on age, with improvement seen only in transplant recipients older than 50 years
21]. A previous study by Zoungas, et al. observed aortic PWV in patients over 1 year
showing a slight improvement, but the majority of these patients were on cyclosporine
15]. Our study has similar findings but in tacrolimus treated patients, which is important
since tacrolimus is the most commonly prescribed calcineurin inhibitor, used as the
initial choice in 91 % of patients in the United States 1]. To our knowledge this is the first study to report carotid PWV in a cohort entirely
maintained on tacrolimus of this duration. A Japanese study of 58 patients on tacrolimus
followed only up to 6 months post transplantation showed a decrease in brachial-ankle
PWV in a low risk population of younger (mean age 40.5 years) kidney transplant recipients
22].

In contrast to our study, a study in Poland found that carotid PWV increased with
time post transplantation, but these patients were already a median time of 36 months
post transplantation at time of enrollment, differing from our population of newly
transplanted patients. Similar PWV values to those in our study were observed in the
61 kidney transplant recipients with an eGFR of 55 mL/min/1.73 m
²
, where the initial measured carotid PWV was 9.1 m/s. In this group, however, PWV
increased to 9.8 m/s when measured 24 months later 23]. One possible explanation for this finding was the prolonged exposure to transplant
immunosuppression. Indeed, some studies have examined the effects of different classes
of immunosuppression on aortic stiffness. In a randomized study in France, low cardiovascular
risk groups of newly transplanted kidney patients were maintained on cyclosporine
or randomized to sirolimus at week 12 and followed for a variety of cardiovascular
related outcomes, including carotid PWV, for 1 year. Those in the sirolimus group
had significantly lower PWV at follow up 24]. Similarly, another study compared carotid PWV in kidney transplant recipients on
belatacept versus calcineurin inhibitors, and found after 5 years post transplantation,
more patients in the calcineurin inhibitor group had a PWV greater than 8.1 m/s than
in the belatacept group 25]. These studies support that calcineurin inhibitors may have more detrimental cardiovascular
effects long term.

Strengths of our study included the prospective longitudinal design and duration of
follow up, including the fact that all patients started follow up at time of their
transplant, so they all had been exposed to transplant immunosuppression the same
length of time. In addition, a large percent of the cohort was black, allowing study
of a population not frequently available in other cohorts of kidney transplant recipients.
A weakness was our inability to adjust for multiple covariates without overfitting
the model due to our relatively small sample size, though we were able to adjust for
all demographics and important cardiovascular risk factors like diabetes and pre-existing
cardiovascular disease. Also due to the small number of cardiovascular events in this
study current cohort, we were not able to test associations of PWV with these. In
addition, overall our population was a low risk population for acute rejection and
low risk for immediate cardiovascular events due to our selection process pre transplant.