Chronic Kidney Disease, Metabolic Acidosis
Conditions
Keywords
vascular endothelial cells
Brief summary
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.
Interventions
DRUGSodium bicarbonate
Subjects will be treated with oral sodium bicarbonate two to three times per day for a goal serum bicarbonate (HCO3-) of ≥ 23 meq/L.
OTHERControl
subjects will receive no treatment
Sponsors
Denver Health and Hospital Authority
University of Colorado, Denver
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Brachial Artery Flow Mediated Dilation (FMD) | 6 weeks and 12 weeks | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Study Participants Patients will start with sodium bicarbonate treatment then switch to control (no treatment)
Sodium bicarbonate: Subjects will be treated with oral sodium bicarbonate two to three times per day for a goal serum bicarbonate (HCO3-) of ≥ 23 meq/L.
Control: subjects will receive no treatment | 20 |
| Total | 20 |
Baseline characteristics
| Characteristic | Study Participants |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 20 Participants |
| Region of Enrollment United States | 20 participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 11 / 20 | 0 / 20 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 |
Outcome results
Primary
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.
Time frame: 6 weeks and 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment | Change in Brachial Artery Flow Mediated Dilation (FMD) | 1.1 absolute change in percent FMD | Standard Deviation 2.6 |
| Control | Change in Brachial Artery Flow Mediated Dilation (FMD) | -0.7 absolute change in percent FMD | Standard Deviation 1.9 |