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

University of Colorado Denver (CU Denver)

Status and phase: Enrolling; Phase 4

Conditions: Kidney Transplant; Complications; Metabolic Acidosis; Vascular Diseases

Treatments: Drug: Placebo; Drug: Sodium bicarbonate

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT05005793

21-3447

R01DK130255 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Enrollment: 120 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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120 participants in 2 patient groups, including a placebo group

Sodium bicarbonate

Experimental group

Description:

Oral sodium bicarbonate at a dose of 0.5 mEq/kg-lean body weight/day

Treatment:

Drug: Sodium bicarbonate

Placebo

Placebo Comparator group

Description:

Oral placebo at a dose of 0.5 mEq/kg-lean body weight/day

Treatment:

Drug: Placebo