Impact of Arterial Stiffness and Central Aortic Blood Pressure on Kidney Transplant Outcomes.

Chronic kidney disease (CKD) is a significant public health problem in United States,
particularly in southern states like Louisiana. People with CKD and end-stage renal disease
(ESRD) have a poor survival compared with general population, and this is primarily due to a
higher prevalence of cardiovascular disease in this population. Almost 50% of deaths in
patients with CKD are attributable to cardiovascular disease. The prevalence of cardiac
arrhythmias, sudden cardiac death (SCD), myocardial infarction, congestive heart failure
(CHF), stroke and peripheral arterial disease is all more common in patients with CKD
compared with general population.

The mechanism behind the increased cardiovascular risk in this population is complex but
there is a strong evidence to suggest that changes in arterial stiffness play a central
role. It is known that patients with CKD and ESRD have increased arterial and aortic
stiffness. Examination of the aorta and conduit arteries from patients with CKD reveals
features of arteriosclerosis, a disease of the arterial medial layer. Increased collagen
content, collagen cross-linking, loss of elastin, and hyperplasia and hypertrophy of
vascular smooth muscle cells results in arterial wall hypertrophy which together with medial
calcification promotes increased stiffness. The causes of arteriosclerosis in CKD include
hypertension due to sodium retention, oxidative stress, inflammation, production of advanced
glycation end products, together with activation of the renin-angiotensin-aldosterone and
sympathetic nervous systems. In addition, arterial stiffness exhibits a dynamic functional
component. Endothelial dysfunction resulting from high levels of oxidative stress and uremic
toxins, such as asymmetrical dimethyl arginine, contributes significantly to increased
arterial stiffness. Increased arterial stiffness causes adverse morphological change in the
left ventricle which is believed to be the basis for CHF, lethal arrhythmia, SCD and
thrombo-embolic stroke.

Arterial stiffness as measured by aortic pulse wave velocity (aPWV) and augmentation index
(AIx), is a surrogate marker of cardiovascular organ damage, and is significantly associated
with the future risk of clinical events. In addition, some studies have demonstrated that
aPWV is an independent and powerful predictor of all-cause and cardiovascular mortality in
patients on dialysis. Reduction of aPWV, mainly by use of an ACE-inhibitor, is associated
with an improved survival in dialysis patients. These findings suggest that arterial
stiffness is not merely a marker of arterial damage but a potentially reversible factor
contributing to mortality in dialysis patients. There is strong cross-sectional evidence
that arterial stiffness increases as glomerular filtration rate (GFR) falls. In the general
population, among treated hypertensives, even minimally impaired baseline renal function
(serum creatinine >90μmol/l) is associated with an increased rate of aortic stiffening.
Conversely, arterial stiffness has also been established in a number of studies as a
significant risk factor for CKD progression.

In addition to arterial stiffness, elevated central aortic blood pressure and central pulse
pressure have been shown to increase the risk of progression of CKD to ESRD. In patients
with CKD, central aortic pulse pressure also positively and independently correlate with
increasing brachial pulse pressure, older age, female sex, and the presence of diabetes
mellitus. Furthermore central blood pressure is more strongly related than standard BP
measured at the brachial arteries (brachial blood pressure) to concentric left ventricular
hypertrophy and carotid artery hypertrophy as well as to future cardiovascular events.

Kidney transplantation prolongs the survival compared with dialysis, but cardiovascular
disease remains the foremost cause of death post-transplant. Although, successful kidney
transplant has been shown to improve arterial stiffness post-transplant, we do not know to
what extent the pre-transplant arterial stiffness and central aortic blood pressure and
their improvement post-transplant impact the cardiovascular and allograft outcomes. In
addition, it is unclear what transplant related factors are associated with improvement in
arterial stiffness and central aortic blood pressure post-transplant.

The goals of our study are:

1. To determine if pre-transplant central blood pressure and aortic stiffness impact
post-transplant cardiovascular and kidney allograft outcomes.

2. To determine whether the changes in central blood pressure and aortic stiffness
post-transplant impact cardiovascular and kidney allograft outcomes.

3. To determine the factors associated with improved central aortic blood pressure and
arterial stiffness post-transplant.

Clinical significance of the study:

Since, arterial stiffness is not merely a marker of arterial damage but a potentially
reversible factor contributing to mortality, this study may provide us an important insight
into potential factors-both reversible and irreversible associated with arterial stiffness
and central aortic blood pressure as well as cardiovascular morbidity and mortality and
kidney allograft outcomes post-transplant.

Inclusion Criteria:

- Wait-listed kidney transplant candidates who have been on the waiting list for at
least 2 years

Exclusion Criteria: