Alkali Therapy for Kidney Complication

Overseen By Jessica Kendrick, MD MPH

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Colorado, Denver

Must be taking: Immunosuppressants

Must not be taking: Anticoagulants, Alkali therapy

Disqualifiers: Heart failure, Uncontrolled hypertension, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

120 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

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.

Do I need to stop my current medications for the trial?

The trial does not specify if you need to stop your current medications, but you must have a stable immunosuppression and anti-hypertensive regimen before joining. You cannot take medications that interact with the trial's agents, like sildenafil with nitroglycerin.

Is alkali therapy, like sodium bicarbonate, safe for humans?

Sodium bicarbonate is generally safe for humans, but excessive use can lead to problems like high blood pressure, muscle breakdown, and kidney issues. Most people don't experience these problems, but it's important to use it as directed by a healthcare provider. ^{1 2 3 4 5}

How is the drug sodium bicarbonate unique in treating kidney complications?

Sodium bicarbonate is unique because it helps correct acid levels in the body, which can preserve kidney function in chronic kidney disease (CKD) patients. Unlike other treatments, it specifically targets metabolic acidosis (a condition where the body produces too much acid or the kidneys cannot remove enough acid) and may reduce harmful substances like angiotensin II that can damage the kidneys. ^{1 5 6 7 8}

What data supports the effectiveness of the drug sodium bicarbonate for kidney complications?

Research shows that sodium bicarbonate can help protect kidney function in people with chronic kidney disease and acute kidney injury by correcting acid imbalance and preventing further damage. ^{1 5 9 10 11}

Who Is on the Research Team?

Jessica Kendrick, MD MPH

Principal Investigator

University of Colorado Denver | Anschutz

Are You a Good Fit for This Trial?

This trial is for kidney transplant recipients aged 18-80 with stable health, not on conflicting meds or treatments, and a BMI under 40. They should have had their transplant at least a year ago, be on specific immunosuppressants, and have certain levels of serum bicarbonate and eGFR—a measure of kidney function.

Inclusion Criteria

Your body mass index (BMI) is less than 40 kg/m2.

Your blood test results show a normal level of bicarbonate on two different days.

Your kidney function, measured by eGFR, needs to be at least 45 ml/min/1.73m2.

Exclusion Criteria

I regularly use supplemental oxygen.

I have not taken daily oral alkali like baking soda in the last 3 months.

I am currently taking blood thinners.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive sodium bicarbonate or placebo for 12 months to assess effects on vascular and graft function

12 months

Regular visits for monitoring and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Sodium bicarbonate

Trial Overview The study tests if sodium bicarbonate can improve heart and graft health in those who've received a kidney transplant. It's a double-blind study where half the participants will get sodium bicarbonate and the other half a placebo for one year to compare effects.

How Is the Trial Designed?

Group I: Sodium bicarbonate Experimental Treatment 1 Intervention

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

Group II: Placebo Placebo Group 1 Intervention

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

Sodium bicarbonate is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Sodium bicarbonate for:

• Metabolic acidosis
• Antacid
• Heartburn relief

Approved in European Union as Sodium bicarbonate for:

• Metabolic acidosis
• Antacid

Approved in Canada as Sodium bicarbonate for:

• Metabolic acidosis
• Antacid

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Published Research Related to This Trial

In a multicenter pilot trial involving 194 adults with chronic kidney disease (CKD), both higher-dose (0.8 meq/kg) and lower-dose (0.5 meq/kg) oral sodium bicarbonate (NaHCO3) were well tolerated over 28 weeks, showing no significant differences in adverse events or hospitalizations compared to placebo.

The higher dose of NaHCO3 resulted in a greater increase in serum bicarbonate levels and a reduction in urinary ammonium excretion, but it also led to a larger increase in urinary albumin/creatinine ratio (ACR), suggesting that while it may be effective, careful monitoring of kidney function is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized Trial Comparing the Safety, Adherence, and Pharmacodynamics Profiles of Two Doses of Sodium Bicarbonate in CKD: the BASE Pilot Trial. Raphael, KL., Isakova, T., Ix, JH., et al.[2021]

Sodium bicarbonate significantly reduces the risk of contrast-induced nephropathy (CIN) in patients with pre-existing renal insufficiency, as shown in a meta-analysis of 20 randomized controlled trials involving 4280 participants.

While sodium bicarbonate is effective in preventing CIN, it does not lower the risks of dialysis or mortality, indicating that it does not improve overall clinical outcomes for patients affected by CIN.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy of sodium bicarbonate in preventing contrast-induced nephropathy in patients with pre-existing renal insufficiency: a meta-analysis. Zhang, B., Liang, L., Chen, W., et al.[2019]

Rats that were pretreated with sodium bicarbonate showed significant protection against kidney damage from renal artery occlusion, with lower serum creatinine levels compared to control rats, indicating its efficacy in preventing acute renal failure.

The protective effect of sodium bicarbonate does not appear to be due to systemic alkalosis or sodium loading, as similar results were observed with acetazolamide, suggesting a unique mechanism of action for bicarbonate in renal protection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of sodium bicarbonate preloading on ischemic renal failure. Atkins, JL.[2022]

A systematic review of 6 randomized controlled trials involving 312 patients found that sodium bicarbonate therapy significantly improved kidney function in patients with chronic kidney disease (CKD), leading to a decrease in serum creatinine and an increase in glomerular filtration rate (GFR).

Long-term alkali therapy was associated with a lower risk of needing dialysis, indicating potential benefits in slowing CKD progression, while no adverse effects on blood pressure medication were noted.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short- and long-term effects of alkali therapy in chronic kidney disease: a systematic review. Susantitaphong, P., Sewaralthahab, K., Balk, EM., et al.[2021]

There is currently no randomized controlled trial evidence supporting the use of sodium bicarbonate for treating acute kidney injury (AKI), despite its common recommendation due to associated acidosis.

The review highlights an urgent need for well-conducted randomized controlled trials to evaluate the efficacy and safety of sodium bicarbonate in patients with AKI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sodium bicarbonate supplements for treating acute kidney injury. Hewitt, J., Uniacke, M., Hansi, NK., et al.[2023]

Sodium bicarbonate is generally safe for oral use, with no documented toxicity in emergency medicine literature, but excessive intake can lead to serious health risks such as metabolic alkalosis and hypernatremia.

A case study highlighted the potential dangers of chronic excessive bicarbonate ingestion, showing that it can lead to multiple hospital admissions due to complications like hyperkalemia and disruption of calcium and phosphorus metabolism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute toxicity from baking soda ingestion. Thomas, SH., Stone, CK.[2019]

Long-term sodium bicarbonate therapy can slightly slow down the loss of kidney function in patients with chronic kidney disease (CKD) and may help reduce the risk of progressing to end-stage renal disease, based on meta-analyses of lower-quality randomized controlled trials.

However, therapy lasting 1 year or less may not provide any benefits, indicating that longer treatment durations are necessary for potential effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is bicarbonate therapy effective in preventing CKD progression? Ahmad, H., Wertin, T., Zhang, Y., et al.[2022]

A patient who ingested over 50 grams of sodium bicarbonate daily for 40 years developed severe health issues, including metabolic alkalosis, epileptic convulsions, and end-stage renal failure requiring hemodialysis.

Kidney biopsy revealed significant damage, including mesangial proliferative glomerulonephritis and arterial wall thickening, indicating that long-term sodium bicarbonate use can lead to serious renal complications and chronic kidney disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Forty years abuse of baking soda, rhabdomyolysis, glomerulonephritis, hypertension leading to renal failure: a case report. Forslund, T., Koistinen, A., Anttinen, J., et al.[2021]

In a study of 108 patients with stage 3 chronic kidney disease (CKD), dietary alkali treatment using sodium bicarbonate or base-producing fruits and vegetables helped preserve kidney function (eGFR) over 3 years compared to usual care.

The treatment not only increased plasma total CO2 levels but also reduced kidney angiotensin II activity, suggesting that even mild metabolic acidosis can be managed effectively to protect kidney health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of metabolic acidosis in patients with stage 3 chronic kidney disease with fruits and vegetables or oral bicarbonate reduces urine angiotensinogen and preserves glomerular filtration rate. Goraya, N., Simoni, J., Jo, CH., et al.[2022]

In a study involving 34 healthy volunteers, potassium sodium hydrogen citrate (PSHC) was found to significantly increase urine pH levels compared to sodium bicarbonate (NaHCO3), indicating that PSHC is more effective for urinary alkalization.

The study also revealed a natural circadian rhythm in urine pH, with both PSHC and NaHCO3 elevating urine pH levels without disrupting this rhythm, suggesting that PSHC can be used effectively without adverse effects on the body's natural processes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison potassium sodium hydrogen citrate with sodium bicarbonate in urine alkalization: a prospective crossover-controlled trial. Xue, W., Cheng, J., Zhao, J., et al.[2023]

Oral sodium bicarbonate significantly increases serum bicarbonate levels and slows the decline in kidney function (eGFR) in patients with chronic kidney disease (CKD), based on a systematic review of 1853 patients.

The treatment also leads to a notable reduction in systolic and diastolic blood pressure, suggesting potential cardiovascular benefits, while showing no significant adverse effects on body weight or muscle mass.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effects of Oral Sodium Bicarbonate on Renal Function and Cardiovascular Risk in Patients with Chronic Kidney Disease: A Systematic Review and Meta-Analysis. Cheng, F., Li, Q., Wang, J., et al.[2023]

Citations

1. United States pubmed.ncbi.nlm.nih.gov

A Randomized Trial Comparing the Safety, Adherence, and Pharmacodynamics Profiles of Two Doses of Sodium Bicarbonate in CKD: the BASE Pilot Trial. [2021]

2. England pubmed.ncbi.nlm.nih.gov

The efficacy of sodium bicarbonate in preventing contrast-induced nephropathy in patients with pre-existing renal insufficiency: a meta-analysis. [2019]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Effect of sodium bicarbonate preloading on ischemic renal failure. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Short- and long-term effects of alkali therapy in chronic kidney disease: a systematic review. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Sodium bicarbonate supplements for treating acute kidney injury. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Acute toxicity from baking soda ingestion. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Is bicarbonate therapy effective in preventing CKD progression? [2022]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Forty years abuse of baking soda, rhabdomyolysis, glomerulonephritis, hypertension leading to renal failure: a case report. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Treatment of metabolic acidosis in patients with stage 3 chronic kidney disease with fruits and vegetables or oral bicarbonate reduces urine angiotensinogen and preserves glomerular filtration rate. [2022]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Comparison potassium sodium hydrogen citrate with sodium bicarbonate in urine alkalization: a prospective crossover-controlled trial. [2023]

11. New Zealand pubmed.ncbi.nlm.nih.gov

The Effects of Oral Sodium Bicarbonate on Renal Function and Cardiovascular Risk in Patients with Chronic Kidney Disease: A Systematic Review and Meta-Analysis. [2023]