Study of Sodium Bicarbonate in Kidney Transplant Recipients

Early Phase 1

Completed

• Conditions: Kidney Transplantation
• Interventions: Drug: Sodium bicarbonate

• Registration Number: NCT01225796
• Lead Sponsor: University of Utah

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2010-10-15
• Study First Submitted QC: 2010-10-19
• Study First Posted: 2010-10-21
• Study Start: 2010-11
• Primary Completion: 2012-11
• Study Completion: 2012-11
• Status Verified: 2016-04
• Last Update Submitted: 2016-04-05
• Last Update Posted: 2016-04-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 29

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sodium bicarbonate	Sodium bicarbonate	This group will receive oral sodium bicarbonate 650mg three times daily for 6 months.

Primary Outcome Measures

Name	Time	Method
Urinary transforming growth factor-beta1	6 months	This is considered a surrogate marker of chronic allograft nephropathy (tubulointerstitial fibrosis).

Secondary Outcome Measures

Name	Time	Method
urinary ammonia excretion	6 months	a component of urinary acid excretion

Trial Locations

Locations (1)

University of Utah; 🇺🇸 Salt Lake City, Utah, United States