Lower serum bicarbonate levels, even within the normal laboratory range, in kidney transplant recipients (KTRs) are associated with an increased risk of graft loss, cardiovascular events and mortality. Because acid retention is common in KTRs, it is plausible that alkali therapy in KTRs may also result in improved vascular and graft function. The investigators will perform a randomized, double-blinded, placebo-controlled, 12 month study in 120 KTRs to examine the effect of sodium bicarbonate therapy on surrogate markers of CVD and graft function. The overall hypothesis is that treatment with bicarbonate will improve indicators of vascular and graft function in KTRs by decreasing complement activation.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
120
Oral sodium bicarbonate at 0.5 mEq/kg-lean body weight/day
Placebo at 0.5 mEq/kg-lean body weight/day
University of Colorado
Aurora, Colorado, United States
RECRUITINGChange in Brachial artery flow mediated dilation at 12 months
Brachial artery FMD will be determined using high-resolution ultrasonographyECG-gated end-diastolic ultrasound images and Doppler flow of the brachial artery will be acquired during baseline and FMD conditions. For FMD, reactive hyperemia will be produced by inflating a pediatric BP cuff around the forearm to 250 mmHg for 5 minutes followed by rapid deflation.
Time frame: Baseline and 12 months
Change in Large elastic artery stiffness and compliance at 12 months
transcutaneous custom tonometers (Noninvasive hemodynamics Workstation, Cardiovascular Engineering Inc., Norwood, MA) will be positioned at the aorta and femoral artery to measure aortic pulse wave velocity.
Time frame: Baseline and 12 months
Change in Tubular atrophy at 12 months
Kidney transplant biopsies will be performed. Morphometric analysis will be performed using trichrome and Sirius Red to determine tubular atrophy. All imaging will be done using an Aperio scanner.
Time frame: Baseline and 12 months
Change in participant plasma and urine complement activation fragment levels at 12 months
Complement activation fragments (Ba, C4a, C3a, C5a, sC5b-9) will be measured at the University of Colorado Exsera Biolab located on the Anschutz Medical Campus.
Time frame: Baseline and 12 months
Change in interstitial fibrosis at 12 months
Kidney transplant biopsies will be performed. Morphometric analysis will be performed using trichrome and Sirius Red to determine interstitial fibrosis.
Time frame: Baseline and 12 months.
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