Metabolic Acidosis and Vascular Function in Patients With Chronic Kidney Disease

Study Overview
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Brief Summary
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Cardiovascular disease (CVD) is the leading cause of death in patients with chronic kidney disease (CKD) and large artery damage is a major factor that contributes to death. Metabolic acidosis is a common complication of CKD resulting from an inability of the diseased kidney to excrete the daily dietary acid load and it is associated with all-cause mortality in patients with CKD. However, the effect of treatment of metabolic acidosis with oral sodium bicarbonate on endothelial dysfunction and arterial stiffness in patients with CKD has not been evaluated. The investigators propose a prospective, randomized, controlled, open-label 14-week crossover pilot study examining the effect of treatment of metabolic acidosis with oral sodium bicarbonate on vascular endothelial function in 20 patients with CKD stage IV with metabolic acidosis.

Official Title
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Effect of Treatment of Metabolic Acidosis on Vascular Function in Patients With Chronic Kidney Disease: A Pilot Study

Conditions
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Metabolic Acidosis, Chronic Kidney Disease

Intervention / Treatment
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* Drug: Sodium bicarbonate
* Other: Control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Age 40-70 years CKD stage IV (eGFR 15-29 ml/min/1.73m2; stable renal function in the past 3 months) Serum bicarbonate level of < 20 and ≥ 16 meq/L (at least 2 consecutive weekly measurements) Body mass index < 40 kg/m2 (FMD measurements can be inaccurate in severely obese patients) Ability to give informed consent Stable anti-hypertensive, diabetic and lipid lowering regimen for at least one month prior to randomization Exclusion Criteria: Significant comorbid conditions that lead the investigator to conclude that life expectancy is less than 1 year Uncontrolled hypertension Expected to undergo living related kidney transplant in next 6 months Expected to start dialysis in next 3 months Overt congestive heart failure Use of sevelamer Use of calcium carbonate

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 70 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: A: Treatment/Control<br>Patients will start with sodium bicarbonate treatment then switch to control (no treatment) | Drug: Sodium bicarbonate<br>* Subjects will be treated with oral sodium bicarbonate two to three times per day for a goal serum bicarbonate (HCO3-) of ≥ 23 meq/L.<br>Other: Control<br>* subjects will receive no treatment<br>|
| Other: B: Control/Treatment<br>Patients will start with control (no treatment) then switch to sodium bicarbonate treatment | Drug: Sodium bicarbonate<br>* Subjects will be treated with oral sodium bicarbonate two to three times per day for a goal serum bicarbonate (HCO3-) of ≥ 23 meq/L.<br>Other: Control<br>* subjects will receive no treatment<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 (FMD) | The primary endpoint is change in brachial artery FMD between treatment and control conditions. Each treatment period is 6 weeks in duration with a 2 week washout period in between. Outcome measures will be repeated at the beginning and end of each period. | 6 weeks and 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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vascular endothelial cells