Potassium Citrate for Kidney Disease

(BICARb Trial)

Recruiting at 1 trial location

Overseen By Kimberly L Reidy, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Albert Einstein College of Medicine

Must not be taking: Bisphosphonates, Denosumab, others

Disqualifiers: Hyperkalemia, Acid-base imbalance, others

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

Compensation: Varies

Number of Visits: 3

Duration: 6 months

103 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this clinical trial is to test whether potassium citrate improves skeletal health in adults and children with chronic kidney disease. The main questions it aims to answer are: * To evaluate effects of potassium citrate treatment on bone quality and strength. * To evaluate mechanism(s) underlying the effects of potassium citrate on skeletal health. Participants will be asked to: * provide blood, urine and answer questions about health and diet three times during an 8 months period * undergo advanced bone imaging with high resolution-peripheral quantitative CT scan twice during 8 months * take study pills for 4-6 weeks at the beginning of the study to ensure safety * take either potassium citrate or placebo for 6 months during the blinded portion of the study As part of the study, there will be a run-in period followed by the placebo-controlled randomized clinical trial. Researchers will compare the bone imaging between the potassium citrate and the placebo groups at the end of the study.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are currently taking a potassium-lowering agent or certain bone-related medications like bisphosphonates or hormone replacement therapies. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug potassium citrate for kidney disease?

Research shows that potassium citrate is effective in preventing the formation of kidney stones, particularly in patients with conditions like distal renal tubular acidosis. It significantly reduces new stone formation and improves urinary conditions, making it a beneficial treatment for managing kidney stone disease. ^{1 2 3 4 5}

Is potassium citrate safe for humans?

Potassium citrate is generally considered safe when used at therapeutic doses, with good tolerance and no significant changes in blood parameters, except for mild transient metabolic alkalosis (a temporary increase in blood pH). It is well tolerated for conditions like kidney stones and distal renal tubular acidosis, but should be avoided in certain conditions like urinary tract infections and advanced chronic renal failure. ^{1 2 3 6 7}

How does the drug potassium citrate differ from other treatments for kidney disease?

Potassium citrate is unique because it helps prevent kidney stones by increasing urinary citrate levels, which reduces stone formation, and it is particularly effective for conditions like renal tubular acidosis and calcium oxalate nephrolithiasis. Unlike some treatments, it is well-tolerated and can be administered in a slow-release form to maintain consistent urinary citrate levels throughout the day. ^{2 3 8 9 10}

Research Team

Kimberly Reidy, MD

Principal Investigator

Albert Einstein College of Medicine

Eligibility Criteria

This trial is for adults and children over 5 with chronic kidney disease who have normal PTH, phosphorus, and vitamin D levels. Women must use contraception and not be pregnant or breastfeeding. Participants can't join if they have certain metabolic bone diseases, high potassium levels, heart risks on ECG, severe other illnesses affecting acid-base balance, a history of kidney stones or limb amputations.

Inclusion Criteria

Women of childbearing potential must be willing to use one form of effective contraception over the course of the study

My child's kidney function is moderately reduced but not severely.

I have had a menstrual period in the last month.

Exclusion Criteria

I have had a solid or liquid organ transplant.

I have had fractures in both my wrists and shins.

My potassium levels are high or I've had high potassium in the last 6 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Run-in Period

Participants take study pills for 4-6 weeks to ensure safety

4-6 weeks

Treatment

Participants take either potassium citrate or placebo for 6 months during the blinded portion of the study

6 months

3 visits (in-person) for blood, urine, and health/diet assessments; 2 visits (in-person) for advanced bone imaging

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Placebo
• Potassium citrate

Trial Overview The study tests if potassium citrate improves bone health in those with chronic kidney disease by comparing it to a placebo. Over 8 months, participants will take pills for safety checks then either the treatment or placebo for 6 months while undergoing blood tests, diet surveys, and advanced bone scans.

Participant Groups

Group I: Potassium Citrate Experimental Treatment 2 Interventions

Potassium Citrate extended-release tablets 30 mEq twice daily. 1 mEq/kg/day divided into two doses for children to a maximum dose of 30 mEq twice daily. OR (for children who cannot take pills): Potassium citrate and citric acid for oral solution 1 mEq/kg/day divided into two doses to a maximum dose of 30 mEq twice daily

Group II: Placebo Placebo Group 1 Intervention

Placebo capsules identical to the active capsules.

Who Is Running the Clinical Trial?

Albert Einstein College of Medicine

Lead Sponsor

Trials

302

Recruited

11,690,000+

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

Collaborator

Trials

2,513

Recruited

4,366,000+

University of Utah

Collaborator

Trials

1,169

Recruited

1,623,000+

University of Pittsburgh Medical Center

Collaborator

Trials

78

Recruited

77,600+

Columbia University

Collaborator

Trials

1,529

Recruited

2,832,000+

Findings from Research

ADV7103, a new prolonged-release formulation for treating distal renal tubular acidosis (dRTA), demonstrated good safety and tolerability over a 24-month study with only 9 mild gastrointestinal adverse events related to the treatment, and no discontinuations due to adverse effects.

The treatment effectively maintained normal plasma bicarbonate and potassium levels in 69-86% and 83-93% of patients, respectively, while achieving a high adherence rate of over 75% in 79% of participants and an impressive 89% improvement in quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, efficacy, and acceptability of ADV7103 during 24 months of treatment: an open-label study in pediatric and adult patients with distal renal tubular acidosis. Bertholet-Thomas, A., Guittet, C., Manso-Silván, MA., et al.[2021]

In a study of 15 patients treated with granulated potassium citrate for one month, significant biochemical changes were observed, including improvements in serum potassium, creatinine, and urinary pH, citrate, and potassium levels.

The treatment was well tolerated, confirming that potassium citrate is an effective and user-friendly option for preventing oxalocalcium kidney stones.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Granulated potassium citrate in the prevention of calcium oxalate lithiasis]. Campoy Martínez, P., Arrabal Martín, M., Quintero Rodríguez, R., et al.[2013]

Potassium citrate is effective in preventing the formation and relapse of certain types of kidney stones, with a one-year remission rate of 70-75% in patients treated for stone disease.

It is generally safe when used at therapeutic doses, causing only mild transient metabolic alkalosis and no significant changes in blood biochemical parameters, while effectively reducing urine calcium and increasing oxalate calcium phosphate excretion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Therapeutic use of potassium citrate]. Zmonarski, SC., Klinger, M., Puziewicz-Zmonarska, A., et al.[2022]

Potassium citrate therapy significantly reduced new stone formation in patients with mild to moderately severe stone disease, achieving a remission rate of 96% (from 0.52 to 0.02 stones per patient per year, p < 0.001).

In contrast, conservative measures or placebo trials only decreased new stone formation by 54% (from 0.54 to 0.25 stones per patient per year), indicating that potassium citrate provides a more effective treatment beyond standard conservative approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative efficacy of "specific" potassium citrate therapy versus conservative management in nephrolithiasis of mild to moderate severity. Preminger, GM., Harvey, JA., Pak, CY.[2019]

In a study of 9 patients with incomplete distal renal tubular acidosis, oral potassium citrate therapy significantly increased urinary pH and citrate levels while decreasing urinary calcium, which helps prevent kidney stone formation.

Over a mean treatment period of 34 months, none of the patients developed new kidney stones, demonstrating the long-term efficacy of potassium citrate in managing calcium nephrolithiasis associated with this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevention of recurrent calcium stone formation with potassium citrate therapy in patients with distal renal tubular acidosis. Preminger, GM., Sakhaee, K., Skurla, C., et al.[2022]

The 'K+ in CKD' study is a randomized, double-blind trial involving 399 patients with chronic kidney disease (CKD) to investigate the effects of potassium supplementation on kidney function over 2 years.

The study aims to determine if potassium supplementation can protect kidney function and improve cardiovascular outcomes, with safety measures in place to monitor for hyperkalemia during the trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rationale and Design of a Randomized Placebo-Controlled Clinical Trial Assessing the Renoprotective Effects of Potassium Supplementation in Chronic Kidney Disease. Gritter, M., Vogt, L., Yeung, SMH., et al.[2023]

In a study of 114 patients with chronic kidney disease (CKD) or end-stage renal disease (ESRD), a single 30g dose of sodium polystyrene sulfonate (SPS) significantly reduced serum potassium levels by a median of 0.8 mEq/L within 24 hours, indicating its efficacy in treating hyperkalemia.

While SPS was effective in lowering potassium, gastrointestinal side effects were reported in 5% of patients, raising concerns about potential risks associated with its use in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-dose sodium polystyrene sulfonate for hyperkalemia in chronic kidney disease or end-stage renal disease. Hunt, TV., DeMott, JM., Ackerbauer, KA., et al.[2023]

Potassium citrate is an effective treatment for managing various types of kidney stones, including calcium stones associated with renal tubular acidosis and hypocitraturic calcium oxalate nephrolithiasis.

It also helps in treating uric acid stones, demonstrating its broad utility in stone disease management, particularly for patients with specific underlying conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Citrate and renal calculi. Pak, CY.[2013]

In a study involving 43 participants (22 normal volunteers and 21 patients with kidney stones), a slow-release potassium citrate preparation effectively increased urinary citrate levels for up to 12 hours after a single dose, helping to maintain higher citrate levels throughout the day.

Potassium citrate at a dosage of 60 meq/day was able to restore normal urinary citrate levels in most patients with low citrate levels, which is beneficial for preventing kidney stone formation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Augmentation of renal citrate excretion by oral potassium citrate administration: time course, dose frequency schedule, and dose-response relationship. Pak, CY., Skurla, C., Brinkley, L., et al.[2019]

In a study of 8 pediatric patients with distal renal tubular acidosis (RTA), potassium citrate at a dosage of 4 mEq/kg/d effectively corrected most urinary abnormalities associated with nephrolithiasis, particularly reducing elevated urinary saturation for calcium oxalate.

The study found that while potassium citrate normalized several urinary ratios, the elevated urinary saturation for calcium phosphate could not be corrected, indicating that while potassium citrate is beneficial, it may not address all urinary issues in distal RTA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dosage of potassium citrate in the correction of urinary abnormalities in pediatric distal renal tubular acidosis patients. Domrongkitchaiporn, S., Khositseth, S., Stitchantrakul, W., et al.[2013]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Safety, efficacy, and acceptability of ADV7103 during 24 months of treatment: an open-label study in pediatric and adult patients with distal renal tubular acidosis. [2021]

2. Spain pubmed.ncbi.nlm.nih.gov

[Granulated potassium citrate in the prevention of calcium oxalate lithiasis]. [2013]

3. Poland pubmed.ncbi.nlm.nih.gov

[Therapeutic use of potassium citrate]. [2022]

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

Comparative efficacy of "specific" potassium citrate therapy versus conservative management in nephrolithiasis of mild to moderate severity. [2019]

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

Prevention of recurrent calcium stone formation with potassium citrate therapy in patients with distal renal tubular acidosis. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Rationale and Design of a Randomized Placebo-Controlled Clinical Trial Assessing the Renoprotective Effects of Potassium Supplementation in Chronic Kidney Disease. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Single-dose sodium polystyrene sulfonate for hyperkalemia in chronic kidney disease or end-stage renal disease. [2023]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Citrate and renal calculi. [2013]

9. England pubmed.ncbi.nlm.nih.gov

Augmentation of renal citrate excretion by oral potassium citrate administration: time course, dose frequency schedule, and dose-response relationship. [2019]

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

Dosage of potassium citrate in the correction of urinary abnormalities in pediatric distal renal tubular acidosis patients. [2013]