Bicarbonate Administration in Kidney Transplant Recipients

Study Overview
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Brief Summary
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Metabolic acidosis is associated with vascular endothelial dysfunction and is a common complication in patients who have received a kidney transplant. Kidney transplant recipients (KTR) with lower serum bicarbonate levels, even within the normal range, have an increased risk of graft loss and mortality. The investigators propose a prospective, double-blind, randomized, placebo-controlled, 18-week crossover pilot study to examine the effects of sodium bicarbonate on vascular endothelial function, graft function, and cognitive function in 20 KTR patients.

Official Title
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Bicarbonate Administration in Kidney Transplant Recipients

Conditions
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Kidney Transplant; Complications, Metabolic Acidosis

Intervention / Treatment
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* Drug: Sodium Bicarbonate
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years Kidney transplant received at least 1 year ago Serum bicarbonate 20-26 mEq/L on 2 separate measurements (at least 1 day apart) eGFR >45 ml/min/1.73m2 Blood pressure <140/90 mm Hg prior to randomization BMI < 40 kg/m2 (FMD measurements can be inaccurate in severely obese patients). Able to provide consent Stable kidney transplant medication regimen for at least 1 month prior to randomization Stable anti-hypertensive regimen for at least one month prior to randomization Not taking medications that interact with agents administered during experimental sessions (e.g. sildenafil interacts with nitroglycerin). Exclusion Criteria: 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 New York Heart Association Class 3 or 4 heart failure symptoms, known EF ≤30%, or hospital admission for heart failure within the past 3 months · Factors judged to limit adherence to interventions Current participation in another research study Pregnancy or planning to become pregnant or currently breastfeeding Chronic use of supplemental oxygen

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sodium bicarbonate<br>During the treatment period, participants will receive 0.5 mEq/kg-lean body weight (LBW)/day of oral sodium bicarbonate for 8 weeks. | Drug: Sodium Bicarbonate<br>* Participants will take ½ the daily dose of sodium bicarbonate in the morning and the other ½ in the evening.<br>* Other names: Baking soda;|
| Placebo Comparator: Placebo<br>During the control period, participants will take the same number of placebo capsules as if they were assigned 0.5 mEq/kg-LBW/day of sodium bicarbonate. | Other: Placebo<br>* Participants will take ½ the daily dose of a placebo in the morning and the other ½ in the evening.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Brachial Artery Flow-Mediated Dilation | Brachial artery Flow-Mediated Dilation (FMD) will be determined using high-resolution ultrasonography (Toshiba Xario 200) as described originally by Celermajer et al., and more recently by our group. FMD will be measured at the beginning and end of each study period for a total of 4 measurements. ECG-gated end-diastolic ultrasound images and Doppler flow of the brachial artery will be acquired during baseline and FMD conditions. | Baseline, 8, 10, and 18 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Transforming Growth Factor Beta 1 (TGF-B1) | Urinary TGF-B1 will be measured from 24-hour urine collections. It will be measured by a commercially available ELISA (R&D Systems). The within day precision for this assay is 6.7% at 257 pg/ml. All measurements will be performed at the Children's Pediatric CTRC at Children's Hospital Colorado. | Baseline, 8, 10, and 18 weeks | 
| Change in Cognitive Function | Cognitive function will be assessed using the National Institutes of Health (NIH) Toolbox computerized tests to evaluate 1) attention, 2) episodic memory, 3) working memory, 4) language, 5) executive function, and 6) processing speed. | Baseline, 8, 10, and 18 weeks |