Investigations of the Optimum Serum Bicarbonate Level in Renal Disease.

Study Overview
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Brief Summary
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The purpose of this study is to see if treatment with sodium bicarbonate will lower urine levels of proteins that are indicators of kidney damage in people with diabetes who also have chronic kidney disease.

Detailed Description
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Diabetic chronic kidney disease (CKD) is a common problem in Veterans and progresses to end-stage renal disease in many people. It is important to identify treatment strategies that will help prevent the progression of CKD to overt kidney failure. The purpose of this study is to see if sodium bicarbonate reduces urinary markers of kidney damage in Veterans with diabetic CKD and normal serum bicarbonate levels.

Official Title
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Investigations of the Optimum Serum Bicarbonate Level in Renal Disease

Conditions
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Chronic Renal Insufficiency, Diabetes Mellitus

Intervention / Treatment
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* Drug: Sodium bicarbonate
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Veteran Age older than 18 years Diabetes mellitus Serum bicarbonate 22 - 28 mmol/L on the most recent measurement within the past six months Stage 2, 3, or 4 CKD (defined as estimated glomerular filtration rate (eGFR) 15 - 89 ml/min/1.73m2 using the CKD-Epidemiology equation) Urinary albumin:creatinine ratio > 30 mg/gm on the most recent sample within the past 12 months. Exclusion Criteria: Lean body weight > 100 kg Use of oral medications typically prescribed to raise low serum bicarbonate levels (i.e. sodium bicarbonate, sodium citrate, potassium citrate). Serum potassium < 3.5 meq/L at enrollment visit Use of 5 or more antihypertensive agents, regardless of the indications of each agent Systolic blood pressure > 140 mmHg or diastolic blood pressure > 90 mmHg at the enrollment or baseline visit Diagnosis of congestive heart failure with current, active Class III or IV New York Heart Association symptoms. Significant fluid overload such that it is unsafe in the opinion of the PI for the patient to participate in the trial chronic gastrointestinal disorder or any other factors judged to be likely to limit adherence to interventions (i.e. alcoholism, a history of missing clinic visits) Chronic immunosuppressive therapy for transplanted organs or other indications Individuals who are currently a member of a vulnerable population (I.e. incarcerated, pregnant). 11.Currently participating in another interventional research study

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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Sodium Bicarbonate<br>Participants were prescribed 0.5 meq of sodium bicarbonate per 1 kilogram of lean body weight daily for six months | Drug: Sodium bicarbonate<br>* Participants will receive 0.5 meq of sodium bicarbonate per 1 kilogram of lean body weight daily. The total amount will be divided into twice daily doses.<br>|
| Placebo Comparator: Placebo<br>Participants were prescribed an identical number of placebo tablets had they been assigned to the intervention, and took this daily for six months. | Drug: Placebo<br>* Participants will receive an identical number of placebo tablets had they been assigned to the intervention. Placebo will be divided into twice daily doses and receive this for six months.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Urinary Transforming Growth Factor Beta 1 (TGF-b1) | Urinary TGF-b1 is considered a marker of renal fibrosis | The mean of the 3-month and 6-month urinary TGF-b1 measurement will be compared to the baseline value between the groups. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Urinary Levels of Kidney Injury Molecule-1 (KIM-1) | KIM-1 is a marker of of kidney injury. | The mean of the 3-month and 6-month measurements will be compared to the baseline values between the groups. | 
| Change in Urinary Levels of Neutrophil Gelatinase-associated Lipocalin (NGAL) | NGAL is a marker of kidney injury | The mean of the 3-month and 6-month measurements will be compared to the baseline values between the groups. | 
| Change in Urinary Levels of Fibronectin | Fibronectin is a marker of kidney injury. | The mean of the 3-month and 6-month measurements will be compared to the baseline values between the groups. | 
| Change in Urinary Albumin Levels | Urinary albumin is a marker of kidney damage | The mean of the 3-month and 6-month measurements will be compared to the baseline values between the groups. | 
| Change in Estimated Glomerular Filtration (eGFR) | eGFR is a measure of kidney function | The mean of the 3-month and 6-month measurements will be compared to the baseline values between the groups. |