Study of Sodium Bicarbonate in Kidney Transplant Recipients

Study Overview
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Brief Summary
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The purpose of this study is to compare the effect of sodium bicarbonate versus no sodium bicarbonate treatment on urinary ammonia levels and urinary transforming growth factor-beta1 (TGF-beta1) excretion in renal transplant patients with low-to-normal serum bicarbonate levels (20 - 28 mmol/L).

Detailed Description
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Renal allograft survival ten years after transplant is only about 50%. In people with non-transplant chronic kidney disease (CKD), sodium bicarbonate treatment seems to delay progressive decline in kidney function in those with low serum bicarbonate levels (metabolic acidosis). This may be because sodium bicarbonate reduces renal ammonia production and hence fibrosis. Observational evidence suggests that people with CKD and low-normal serum bicarbonate levels might also benefit from sodium bicarbonate treatment. TGF-beta1 levels seem to be an important predictor of chronic allograft nephropathy, and alkalinizing agents may have an effect on TFG-beta1 excretion. Retrospective analysis of participants in the African American Study of Kidney Disease and Hypertension showed the lowest risk of CKD progression was among those having baseline serum bicarbonate levels in the range of 28-30 mmol/L. Recent studies in people with pre-transplant CKD have suggested that increasing low serum bicarbonate levels (< 22 mmol/L) with alkalinizing agents such as sodium bicarbonate and sodium citrate may reduce CKD progression. Design: this is an open-label randomized study testing the effect of a six-month intervention with sodium bicarbonate 650 mg orally thrice daily versus no sodium bicarbonate treatment on renal ammonia excretion and urinary TGF-beta1. Visits will occur at baseline, 3 months, and 6 months. At each follow-up visit, the study coordinator or principal investigator will review a medical questionnaire with the participant and collect a sample of blood and urine for analysis of urinary TGF-beta1, metabolic panel, pH, urinary net acid excretion, urinary bicarbonate and urinary ammonia.

Official Title
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Randomized Trial of Sodium Bicarbonate in Renal Transplant Recipients With Low-normal Serum Bicarbonate Levels

Conditions
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Kidney Transplantation

Intervention / Treatment
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* Drug: Sodium bicarbonate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Renal transplant recipients Age 21-75 years Six months since the time of the most recent transplant Serum bicarbonate 20-28mM on the two most recent serum measures with the last six months Stable creatinine Exclusion Criteria: Systolic blood pressure > 140mmHg Diastolic blood pressure > 90mmHg Known ejection fraction <50% Clinical diagnosis of heart failure Use of >3 antihypertensive agents > 1+ edema Use of alkali in the preceding 3 months History of noncompliance with clinic visits

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 75 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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sodium bicarbonate<br>This group will receive oral sodium bicarbonate 650mg three times daily for 6 months. | Drug: Sodium bicarbonate<br>* Sodium bicarbonate 650mg by mouth three times daily for 6 months.<br>|
| No Intervention: Control<br>This group will not receive any sodium bicarbonate. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urinary transforming growth factor-beta1 | This is considered a surrogate marker of chronic allograft nephropathy (tubulointerstitial fibrosis). | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| urinary ammonia excretion | a component of urinary acid excretion | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bicarbonate, Chronic allograft nephropathy, Urinary TGF-beta, Urinary acid excretion