Acid-Base Compensation in Chronic Kidney Disease

Study Overview
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Brief Summary
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The purpose of this study is to evaluate changes in urine net acid excretion, blood pressure and body chemistry that occur when the dietary acid load is lowered by using a drug/dietary supplement similar to baking soda. This may be important for patients with kidney disease because they may have difficulty removing all of the dietary acid load from the body in the urine. Participants with and without kidney disease will be recruited. Each participant will be fed a controlled diet for one week with sodium bicarbonate and for one week without sodium bicarbonate to evaluate these changes. The investigators will also determine if the effect of dietary acid load reduction is different in patients with kidney disease compared to those without kidney disease.

Official Title
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Acid-Base Compensation in Chronic Kidney Disease: Measurement and Physiologic Impact

Conditions
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Chronic Kidney Disease

Intervention / Treatment
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* Drug: Sodium bicarbonate
* Other: Controlled diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: estimated glomerular filtration rate ≥30 ml/min/1.73m2 serum bicarbonate 20-28 mEq/L Exclusion Criteria: diabetes mellitus uncontrolled hypertension or recent (<3 weeks) titration of blood pressure medications clinically significant volume overload on screening physical examination selected medical conditions other than kidney disease and hypertension (active cancer, chronic liver failure, moderate to severe COPD, New York Heart Association class 2 or greater congestive heart failure, obstructive sleep apnea requiring nightly continuous positive airway pressure, solid organ transplant) use of alkali supplementation body mass index <18.5 or >40 kg/m2 ideal body weight <45.5 kg anemia at screening (hematocrit <29% in participants with kidney disease or <33% in healthy participants) pregnancy or breastfeeding allergies, intolerance or unwillingness to consume foods or supplement provided in feeding menu serum calcium less than 8.6 mg/dl on screening laboratories

Ages Eligible for Study
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Minimum Age: 22 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Controlled diet first<br>In this arm participants will first consume a controlled diet plus added table salt (sodium chloride) for one week. They will then consume an identical controlled diet plus sodium bicarbonate for one week. Sodium bicarbonate will be dosed as 2,600 mg divided three times daily if ideal body weight is <70 kg or 3,250 mg divided three times daily if ideal body weight is ≥70 kg. Added table salt will match the sodium content of the sodium bicarbonate dose (i.e. 31 or 39 mEq/day). | Drug: Sodium bicarbonate<br>* Drug/dietary supplement is used in a crossover design to lower the nonvolatile acid load of the diet compared to the control period.<br>* Other names: Baking powder;Other: Controlled diet<br>* Diet without sodium bicarbonate supplementation<br>|
| Experimental: Sodium bicarbonate first<br>In this arm participants will first consume a controlled diet plus sodium bicarbonate for one week. They will then consume an identical controlled diet plus added table salt (sodium chloride) for one week. Sodium bicarbonate will be dosed as 2,600 mg divided three times daily if ideal body weight is <70 kg or 3,250 mg divided three times daily if ideal body weight is ≥70 kg. Added table salt will match the sodium content of the sodium bicarbonate dose (i.e. 31 or 39 mEq/day). | Drug: Sodium bicarbonate<br>* Drug/dietary supplement is used in a crossover design to lower the nonvolatile acid load of the diet compared to the control period.<br>* Other names: Baking powder;Other: Controlled diet<br>* Diet without sodium bicarbonate supplementation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in ambulatory blood pressure | Change in mean 24 hour systolic and diastolic blood pressure comparing the end of the controlled feeding plus sodium bicarbonate period to the end of the controlled feeding plus table salt period. | Measured at the end of each week of intervention (i.e. one week apart) | 
| Change in urine net acid excretion | Change in urine net acid excretion comparing the end of the controlled feeding plus sodium bicarbonate period to the end of the controlled feeding plus table salt period. | Urine net acid excretion will be measured at three timepoints over approximately 3 weeks (i.e. 2 weeks of intervention plus one week baseline data collection/run-in) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in clinic blood pressure | Change in average of three readings of systolic and diastolic blood pressure will be evaluated comparing the end of the controlled feeding plus sodium bicarbonate period to the end of the controlled feeding plus table salt period. | Clinic blood pressure will be measured at multiple timepoints over approximately 3 weeks (i.e. 2 weeks of intervention plus one week baseline data collection/run-in) | 
| Change in plasma nitric oxide metabolites | Change in nitric oxide metabolites comparing the end of the controlled feeding plus sodium bicarbonate period to the end of the controlled feeding plus table salt period. | Measured at the end of each week of intervention (i.e. one week apart) up to 3 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Kidney Diseases, Renal Insufficiency, Chronic, Dietary nonvolatile acid load, Blood pressure, Urine net acid excretion