Study of Sodium Bicarbonate in Kidney Transplant Recipients

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.

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