Effect of Alkali Therapy on Vascular and Graft Function in Kidney Transplant Recipients

Effect of Alkali Therapy on Vascular and Graft Function in Kidney Transplant

Lower serum bicarbonate levels, even within the normal laboratory range, in kidney transplant recipients (KTRs) are associated with an increased risk of graft loss, cardiovascular events and mortality. Because acid retention is common in KTRs, it is plausible that alkali therapy in KTRs may also result in improved vascular and graft function. The investigators will perform a randomized, double-blinded, placebo-controlled, 12 month study in 120 KTRs to examine the effect of sodium bicarbonate therapy on surrogate markers of CVD and graft function. The overall hypothesis is that treatment with bicarbonate will improve indicators of vascular and graft function in KTRs by decreasing complement activation.

Study Overview

• Status: Recruiting
• Conditions: Vascular Diseases; Kidney Transplant; Complications; Metabolic Acidosis
• Intervention / Treatment: Drug: Sodium bicarbonate; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Jessica Kendrick, MD MPH; Phone Number: 3037244837; Email: jessica.kendrick@ucdenver.edu

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • University of Colorado
      • Contact: Jessica Kendrick; Phone Number: 303-724-4837; Email: jessica.kendrick@cuanschutz.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 18-80 years
• Serum bicarbonate 16-24 mEq/L on 2 separate measurements (at least 1 day apart)
• Kidney transplant received 1 year prior to randomization
• eGFR ≥ 45 ml/min/1.73m2 by CKD-EPI equation
• Blood pressure <130/80 mm Hg prior to randomization
• BMI < 40 kg/m2 (FMD measurements can be inaccurate in severely obese patients).
• Able to provide consent
• Immunosuppression regimen consisting of tacrolimus, mycophenolate mofetil and prednisone (95% of patients at University of Colorado are on this regimen)
• Stable immunosuppression regimen for at least three months prior to randomization
• Stable anti-hypertensive regimen for at least one month prior to randomization
• Not taking medications that interact with agents administered during experimental sessions (e.g. sildenafil interacts with nitroglycerin).

Exclusion Criteria:

• Significant comorbid conditions that lead the investigator to conclude that life expectancy is less than 1 year
• Use of chronic daily oral alkali within the last 3 months (including sodium bicarbonate, calcium carbonate or baking soda)
• Uncontrolled hypertension
• Serum potassium < 3.3 or ≥ 5.5 mEq/L at screening
• New York Heart Association Class 3 or 4 heart failure symptoms, known EF ≤30%, or hospital admission for heart failure within the past 3 months
• Nephrotic range proteinuria (urine complement activation fragment measurements may not be accurate with severe proteinuria)
• Factors judged to limit adherence to interventions
• Current participation in another research study
• Pregnancy or planning to become pregnant or currently breastfeeding
• Chronic use of supplemental oxygen
• Use of anticoagulants

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sodium bicarbonate; Oral sodium bicarbonate at a dose of 0.5 mEq/kg-lean body weight/day	Drug: Sodium bicarbonate; Oral sodium bicarbonate at 0.5 mEq/kg-lean body weight/day
Placebo Comparator: Placebo; Oral placebo at a dose of 0.5 mEq/kg-lean body weight/day	Drug: Placebo; Placebo at 0.5 mEq/kg-lean body weight/day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Brachial artery flow mediated dilation at 12 months	Brachial artery FMD will be determined using high-resolution ultrasonographyECG-gated end-diastolic ultrasound images and Doppler flow of the brachial artery will be acquired during baseline and FMD conditions. For FMD, reactive hyperemia will be produced by inflating a pediatric BP cuff around the forearm to 250 mmHg for 5 minutes followed by rapid deflation.	Baseline and 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Large elastic artery stiffness and compliance at 12 months	transcutaneous custom tonometers (Noninvasive hemodynamics Workstation, Cardiovascular Engineering Inc., Norwood, MA) will be positioned at the aorta and femoral artery to measure aortic pulse wave velocity.	Baseline and 12 months
Change in Tubular atrophy at 12 months	Kidney transplant biopsies will be performed. Morphometric analysis will be performed using trichrome and Sirius Red to determine tubular atrophy. All imaging will be done using an Aperio scanner.	Baseline and 12 months
Change in participant plasma and urine complement activation fragment levels at 12 months	Complement activation fragments (Ba, C4a, C3a, C5a, sC5b-9) will be measured at the University of Colorado Exsera Biolab located on the Anschutz Medical Campus.	Baseline and 12 months
Change in interstitial fibrosis at 12 months	Kidney transplant biopsies will be performed. Morphometric analysis will be performed using trichrome and Sirius Red to determine interstitial fibrosis.	Baseline and 12 months.

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Jessica Kendrick, MD MPH, University of Colorado Denver | Anschutz

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2021
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): August 31, 2026

Study Registration Dates

• First Submitted: July 14, 2021
• First Submitted That Met QC Criteria: August 10, 2021
• First Posted (Actual): August 16, 2021

Study Record Updates

• Last Update Posted (Actual): May 29, 2025
• Last Update Submitted That Met QC Criteria: May 28, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Metabolic Diseases; Acid-Base Imbalance; Vascular Diseases; Acidosis
• Other Study ID Numbers: 21-3447; R01DK130255 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: At the conclusion of the study, data, which has been stripped of all personal identification information and coded with a number, will be made available to qualified individuals within the scientific community who apply for data use. The results and outcomes of this study will be made generally available by publication and journal articles submitted to PubMed Central in compliance with NIH access guidelines.
• IPD Sharing Time Frame: At the conclusion of the study, data, which has been stripped of all personal identification information and coded with a number, will be made available to qualified individuals within the scientific community who apply for data use. The results and outcomes of this study will be made generally available by publication and journal articles submitted to PubMed Central in compliance with NIH access guidelines.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No