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Effect of Alkali Therapy on Vascular and Graft Function in Kidney Transplant Recipients

ConditionsMetabolic AcidosisKidney Transplant; ComplicationsVascular Diseases
Trial statusRecruiting
Trial phasePhase 4
Trial typeInterventional
Biological sexAll
Age18-80
SponsorUniversity of Colorado, Denver

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Age 18-80 years

Serum bicarbonate 16-24 mEq/L on 2 separate measurements (at least 1 day apart)

Kidney transplant received 1 year prior to randomization

eGFR ≥ 45 ml/min/1.73m2 by CKD-EPI equation

Disqualifiers

Significant comorbid conditions that lead the investigator to conclude that life expectancy is less than 1 year

Use of chronic daily oral alkali within the last 3 months (including sodium bicarbonate, calcium carbonate or baking soda)

Uncontrolled hypertension

Serum potassium < 3.3 or ≥ 5.5 mEq/L at screening

Trial design

Design model

Parallel

Treatments tested in this trial

  • Sodium bicarbonate

    Drug

    Oral sodium bicarbonate at 0.5 mEq/kg-lean body weight/day

  • Placebo

    Drug

    Placebo at 0.5 mEq/kg-lean body weight/day

Treatment groups

120 Participants
are divided into 2 treatment groups
Group A: Sodium bicarbonateExperimental treatment 1 intervention
Group B: PlaceboPlacebo comparator 1 intervention

Trial outcomes

Primary outcomes

1

Change 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

Secondary outcomes

1

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
2

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
3

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
4

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.

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

University of Colorado, Denver

Lead sponsor

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Source ClinicalTrials.gov
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