Oxalate and Citrate Drink for Kidney Stones

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Chicago

Must not be taking: Diuretics, Alkali supplements

Disqualifiers: Uric acid stones, Severe acid-base abnormality, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how compounds called oxalate and citrate, commonly found in food, affect the likelihood of developing kidney stones. The study compares two groups: individuals who have had at least one calcium-based kidney stone and those who have never had kidney stones. Participants must have either experienced kidney stones or never had them and must be able to stop certain medications during the study.

As an unphased trial, this study offers participants the chance to contribute to valuable research that could lead to better prevention strategies for kidney stones.

Will I have to stop taking my current medications?

If you are taking diuretic medication or alkali supplements, you will need to stop them for the duration of the study.

What prior data suggests that oxalate and citrate are safe for kidney stone research?

Research shows that potassium citrate often prevents kidney stones. It generally increases citrate levels in urine, helping to prevent stone formation, and is well-tolerated. While effective, some individuals might experience mild side effects like an upset stomach.

Oxalate, found in certain foods, can contribute to kidney stone formation, especially when combined with calcium in urine. Higher oxalate levels might increase the risk of developing stones. Less research exists on using oxalate as a treatment, so weighing potential risks and benefits is important.

Overall, citrate is considered safe and effective for preventing stones, while the role of oxalate remains less clear and may involve some risk. Participants should stay informed and consult healthcare providers before joining a study. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using oxalate and citrate drinks for kidney stones because these compounds might offer a new way to prevent stones from forming. Unlike standard treatments like pain relievers or surgical interventions, citrate can help dissolve and prevent stones by making urine less acidic, while oxalate levels can be monitored to reduce stone risk. This approach could provide a non-invasive option that targets the chemical balance in the urinary system, potentially reducing the need for more aggressive treatments.

What evidence suggests that this trial's treatments could be effective for kidney stones?

This trial will compare the effects of citrate and oxalate in individuals with and without a history of kidney stones. Studies have shown that citrate can help reduce the risk of kidney stones recurring. Research has found that potassium citrate lowers calcium levels in urine and increases citrate levels, which helps prevent stones. One study demonstrated that potassium-magnesium citrate reduced stone recurrences by raising urine pH and citrate levels.

Oxalate's role is more complex. High oxalate levels are linked to kidney stone formation, so understanding its effects on the body is important. Some studies suggest that managing dietary oxalate may influence kidney stone growth. However, more research is needed to fully understand how oxalate impacts kidney stones. ^{2 4 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults aged 18-70 who either have a history of calcium-based kidney stones or no history at all (controls). Participants should have normal urine oxalate levels. Those with a history of non-calcium stones, severe acid-base issues, or extreme urine citrate levels cannot join.

Exclusion Criteria

You have a history of very high or very low levels of citrate in your urine or severe acid-base imbalance.

I cannot stop taking my diuretic medication or alkali supplements for the study.

You have a history of certain types of kidney stones.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Pre-study Preparation

Participants discontinue certain supplements and medications, complete a 24-hour urine collection and food frequency questionnaire at home

1 week

Study Day

Participants consume a 360mg oral sodium oxalate load and undergo urine and blood sampling over 6 hours

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Citrate
• Oxalate

Trial Overview The study investigates the effects of two dietary compounds, oxalate and citrate, on the likelihood of developing kidney stones. Participants will consume a special drink containing sodium oxalate during an all-day visit to the research clinic.

How Is the Trial Designed?

Group I: Non-kidney stone formers Experimental Treatment 1 Intervention

25 non-stone-forming subjects will be enrolled in this arm.

Group II: Kidney stone formers Experimental Treatment 1 Intervention

25 stone-forming subjects will be enrolled in this arm.

Who Is Running the Clinical Trial?

University of Chicago

Lead Sponsor

Trials

1,086

Recruited

844,000+

Published Research Related to This Trial

In a study involving five calcium oxalate stone formers, the ingestion of minimum doses of potassium citrate significantly increased citraturia and crystallization inhibitory capacity in urine samples.

The most effective timing for taking potassium citrate was after dinner, suggesting that this method could help reduce the risk of kidney stone formation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronopharmacological studies on potassium citrate treatment of oxalocalcic urolithiasis. Grases, F., Conte, A., March, JG., et al.[2019]

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 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 22 patients with calcium oxalate stones, the addition of lemon-tomato juice to their diet significantly reduced urine optical density, indicating a lower risk of stone formation compared to consuming milk alone.

The urine calcium-creatinine ratio was also lower after consuming lemon-tomato juice, suggesting that this dietary intervention may effectively decrease key risk factors for calcium oxalate stone recurrence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of lemon-tomato juice consumption on crystal formation in the urine of patients with calcium oxalate stones: A randomized crossover clinical trial. Gopala, SK., Joe, J., Chandran, J.[2023]

In a study of 64 patients over 3 years, potassium-magnesium citrate significantly reduced the recurrence of calcium oxalate kidney stones, with only 12.9% of patients forming new stones compared to 63.6% in the placebo group.

The treatment lowered the risk of stone recurrence by 85%, demonstrating its efficacy in preventing kidney stones even after accounting for various confounding factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potassium-magnesium citrate is an effective prophylaxis against recurrent calcium oxalate nephrolithiasis. Ettinger, B., Pak, CY., Citron, JT., et al.[2019]

The combination of potassium-sodium citrate (KNa-Cit) and magnesium oxide (MgO) significantly increases urinary excretion of citrate, magnesium, and potassium in both healthy individuals and patients with calcium oxalate stones, suggesting enhanced inhibition of stone formation.

In patients with recurrent calcium oxalate stones, this combination not only increased beneficial urinary parameters but also reduced oxalate levels by 66.5%, indicating a potential for improved management of stone recurrence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changes in urinary parameters after oral administration of potassium-sodium citrate and magnesium oxide to prevent urolithiasis. Kato, Y., Yamaguchi, S., Yachiku, S., et al.[2019]

Many over-the-counter supplements contain more citrate than advertised, with Moonstone® powder showing the highest citrate content per serving (63.9 mEq), which could help prevent kidney stone recurrence.

While Moonstone offers the most citrate, it is more expensive compared to other products like NOW® potassium citrate, which is the least costly option ($0.04/10 mEq alkali citrate), highlighting the need to consider both efficacy and cost when choosing a citrate supplement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alkali Citrate Content of Common Over-the-Counter and Medical Food Supplements. Dai, JC., Maalouf, NM., Hill, K., et al.[2023]

Potassium-magnesium citrate significantly increased urinary pH and citrate levels compared to potassium citrate, suggesting it may be more effective in preventing kidney stones by reducing the saturation of calcium oxalate.

In a study involving five normal subjects and five patients with calcium nephrolithiasis, potassium-magnesium citrate therapy led to a greater reduction in undissociated uric acid and a significant increase in urinary magnesium, indicating enhanced urinary biochemistry for stone prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Physicochemical action of potassium-magnesium citrate in nephrolithiasis. Pak, CY., Koenig, K., Khan, R., et al.[2013]

In a study of 80 patients with calcium oxalate stones and hypercalciuria, potassium citrate (K-CIT) was found to significantly increase urinary citrate levels and effectively reduce calcium excretion, similar to hydrochlorothiazide (HCT).

Both K-CIT and HCT treatments led to significant reductions in 24-hour urine calcium levels, but K-CIT showed a greater increase in citrate excretion, suggesting it may be a beneficial option for preventing stone recurrence in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potassium citrate vs. hydrochlorothiazide to reduce urinary calcium excretion in calcium oxalate stone patients with hypercalciuria: a prospective randomized study. Solak, V., Gökce, Mİ., Yaman, Ö.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4657843/

Effect of Potassium Citrate on Calcium Phosphate Stones ... In a randomized controlled study, potassium and sodium citrate appeared to reduce the risk of stone recurrence after extracorporeal shockwave lithotripsy or ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0085253815330350

Contrasting effects of potassium citrate and sodium ... During potassium citrate therapy, urinary calcium significantly declined from 154 ± 47 mg/day to 99 ± 23 mg/day (P < 0.01) and urinary citrate rose from 398 ± ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9578669/

Citrate salts for preventing and treating calcium containing ... A number of non‐randomised studies have demonstrated a beneficial effect of citrate salts therapy in patients with kidney stones.

4. academic.oup.com academic.oup.com/ckj/article/18/9/sfaf244/8221902

Citrate and calcium kidney stones - Oxford Academic Potassium-magnesium citrate increased urinary citrate levels and pH, resulting in significantly fewer stone recurrences [47]. Barcelo et al.

5. jdc.jefferson.edu jdc.jefferson.edu/cgi/viewcontent.cgi?article=1018&context=tjuhpapers

A Review of Prescription, Over-the-Counter, and Medical Food ... The study found increased urinary outputs and urine pH, citrate and magnesium with decreased urinary calcium and super saturation of uric acid on 24‐ hour urine ...

6. mayoclinic.org mayoclinic.org/drugs-supplements/potassium-citrate-oral-route/description/drg-20074773

Potassium citrate (oral route) - Side effects & dosage Potassium citrate is used to treat a kidney stone condition called renal tubular acidosis. It is also used to prevent kidney stones that may occur with gout.

7. hopkinsmedicine.org hopkinsmedicine.org/health/conditions-and-diseases/kidney-stones

Kidney Stones Citrate supplements, such as potassium citrate, will raise the pH of your urine, making stones, such as those composed of uric acid, less likely to form. If ...

8. emedicine.medscape.com emedicine.medscape.com/article/444968-overview

Hypocitraturia Overview of Potassium Citrate and Calcium ... Hypocitraturia, a low amount of citrate in the urine, is an important risk factor for kidney stone formation.