Long term evolution of endothelial function during kidney transplantation

Abstract

BackgroundEndothelial dysfunction is an important precursor to the development of atherosclerosis, and has been suggested to play a role in the increased cardiovascular risk in patients with end stage renal disease. Endothelial function improves rapidly following post kidney transplantation, but the long term change remains unclear. Hypothesizing that endothelial function would remain improved long term post kidney transplantation, we evaluated the longitudinal change of endothelial function, measured by flow-mediated dilation (FMD) of the brachial artery, from months 1 to 24 post transplantation. Given the previously reported association of fibroblast growth factor 23 (FGF-23) with endothelial dysfunction, we also examined changes in the association between FGF-23 levels and the change in FMD following kidney transplantation.MethodsWe performed a prospective cohort study of 149 kidney transplant recipients, measuring endothelial function by FMD at months 1, 12, and 24 post-transplant. FGF-23 levels were measured at months 1 and 24 post-transplant. Linear mixed effects models were used to assess both the unadjusted and adjusted outcomes.ResultsThe cohort (mean age 49 ± 13 years) was 74 % male and 75 % white. The median FMD was 6.3 % (IQR: 3.4, 10.2), 5.4 % (IQR: 3.1, 8.5), and 5.6 % (IQR: 3.5, 9.1) at 1, 12, and 24 months, respectively. After adjustment for covariates, compared to month 1, no change occurred in FMD at 12 months (−0.66 %; 95 % CI: −1.81 %, 0.49 %; P = 0.262) or 24 months (−0.25 %; 95%CI: −1.76 %, 1.26 %; P = 0.746). FGF-23 decreased significantly over time (P = 0.024), but there was no significant association between FGF-23 and FMD (P = 0.799).ConclusionEndothelial function remained stable at 12 and 24 months from 1 month post-kidney transplant, indicating that the improved endothelial function seen with transplant is maintained up to 2 years post transplantation. There was also no significant association between FGF-23 and endothelial function following kidney transplantation.

Cytomegalovirus burden improves a predictive model identifying measures of vascular risk in renal transplant recipients and healthy adults

“…First, we establish FMD as a stable prognostic marker of vascular health. Kensinger et al 28 showed that FMD improved 11 months after patients received a kidney transplant although this study was conducted from months 1 to 24 posttransplantation. However, the RTR participants in our cohort were assessed at a median of 7 (baseline) and 10 years (follow‐up) after transplantation.…”

Arterial stiffness but not endothelial dysfunction is associated with multidrug antihypertensive therapy and nondipper blood pressure pattern in kidney transplant recipients

“…[ 13 , 21 , 22 ] Likewise, a cross-sectional study showed significantly lower FMD values in KTRs than in dialysis subjects, [ 12 ] although a recent prospective study demonstrated stable FMD values between first and 24th month post-transplantation. [ 23 ] Furthermore, Sharma et al [ 24 ] reported significant FMD improvement after transplantation; however, the exact time-point of post-transplant FMD measurement was unknown. Finally, increased sympathetic nerve activity in KTRs was proven to be related to decreased distensibility of the muscular type arteries, which contributes to arterial stiffness.…”

Dissecting recipient from donor contribution in experimental kidney transplantation: focus on endothelial proliferation and inflammation

“…The association between oxidative stress, inflammation and CKD is well established ( Tucker et al, 2015 ). Although in humans, endothelial function improves after successful renal transplantation ( Kensinger et al, 2016 ), renal transplant recipients still have poor endothelial function in comparison to the healthy population ( Stadler et al, 2009 ). Immunosuppressant drugs undoubtedly contribute to this effect ( Ovuworie et al, 2001 ).…”