Prevention Strategies for Kidney Stones

Recruiting in Palo Alto (17 mi)

Overseen by Ryan Hsi, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Recruiting

Sponsor: Vanderbilt University Medical Center

Must not be taking: Thiazides, Topiramate, others

Disqualifiers: Pregnancy, Chronic kidney disease, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial compares two methods to prevent kidney stones in patients who have had multiple episodes. One method uses specific urine tests to guide treatment, while the other uses a general treatment approach. Both methods involve diet changes and medications to reduce stone-forming substances in the urine. Recognized medications for preventing kidney stone recurrence include thiazide diuretics, allopurinol, and potassium citrate.

Will I have to stop taking my current medications?

The trial excludes participants who are using specific medications like thiazides, topiramate, xanthine oxidase inhibitors, citrate, and bicarbonate. If you are taking any of these, you may need to stop them to participate.

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

Research shows that potassium citrate is effective in preventing kidney stones, particularly calcium oxalate and calcium phosphate stones, by increasing urinary citrate levels and alkalinizing urine, which helps prevent stone formation. ^{1 2 3 4 5}

Is potassium citrate safe for preventing kidney stones?

Potassium citrate is generally considered safe when used at therapeutic doses, with good tolerance and no significant side effects reported in studies. Some mild changes in blood chemistry may occur, but no serious complications like gastrointestinal upset or cardiopulmonary discomfort have been observed. ^{1 2 3 6 7}

What makes the drug potassium citrate unique for preventing kidney stones?

Potassium citrate is unique because it helps prevent kidney stones by alkalinizing (making less acidic) the urine, which can reduce the formation of certain types of stones like calcium oxalate and uric acid stones. It is particularly effective for patients with low citrate levels in their urine, a condition known as hypocitraturia. ^{1 3 4 5 8}

Research Team

Ryan Hsi, MD

Principal Investigator

Vanderbilt University Medical Center

Eligibility Criteria

This trial is for adults who've had two or more painful kidney stone episodes in the past five years. It's not suitable for those with certain kidney conditions, untreated urinary blockages, specific metabolic disorders, pregnancy, inflammatory bowel disease or related surgeries, sarcoidosis, cystinuria, severe chronic kidney disease (eGFR<60), frequent gout attacks, allergies to study meds or imbalances in blood potassium/sodium.

Inclusion Criteria

I am 18 years old or older.

I have had two or more painful kidney stone episodes in the past 5 years.

Exclusion Criteria

My kidney function is reduced (eGFR<60).

I have a blockage in my urinary system that hasn't been treated.

Known allergy to study medications

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomly assigned to either empiric diet plus thiazide with potassium citrate daily, or to selective diet plus pharmacologic therapy based on 24-hour urine abnormalities.

8 weeks

Baseline, 1 month, and 2 months

Follow-up

Participants are monitored for changes in urinary supersaturation and adverse effects from the treatment strategies.

4 weeks

Treatment Details

Interventions

• Empiric Therapy: Diet (Dietary Modification)
• Empiric Therapy: Drug (Pharmacologic Agent)
• Selective Therapy: Diet (Dietary Modification)
• Selective Therapy: Drug (Pharmacologic Agent)

Trial Overview The study compares two approaches to prevent new kidney stones: 'Selective Therapy' which tailors diet and drugs to individual needs versus 'Empiric Therapy' that uses a general diet and medication plan. Participants are randomly assigned to one of these strategies.

Participant Groups

Group I: Selective Therapy Experimental Treatment 2 Interventions

Diet intervention and drug intervention based on 24 hour urine results

Group II: Empiric Therapy Active Control 2 Interventions

Diet intervention and drug intervention not based on 24 hour urine results

Who Is Running the Clinical Trial?

Vanderbilt University Medical Center

Lead Sponsor

Trials

922

Recruited

939,000+

Jeffrey R. Balser

Vanderbilt University Medical Center

Chief Executive Officer since 2009

MD and PhD from Vanderbilt University

Rick W. Wright

Vanderbilt University Medical Center

Chief Medical Officer since 2023

MD from University of Missouri-Columbia

Findings from Research

In a study of 70 asymptomatic urolithiasis patients, a combination of potassium citrate (K-Cit) and magnesium chloride (MgCl2) significantly reduced urinary stone size compared to K-Cit alone after 4 weeks of treatment.

The mean urinary stone size decreased from 5.1 ± 0.8 mm to 2.5 ± 1.2 mm in the group receiving the combination therapy, indicating that this combination may be a more effective treatment option for managing urinary stones.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluating the effectiveness of adding magnesium chloride to conventional protocol of citrate alkali therapy on kidney stone size. Niroomand, H., Ziaee, A., Ziaee, K., et al.[2020]

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]

K-CITEK, a new potassium-citrate regimen, was found to be equally effective as UROCIT-K in preventing kidney stones, based on a study of 104 patients.

Both treatments showed no significant differences in urinary citrate levels, stone burden, or the frequency of kidney stone events, indicating that K-CITEK is a viable alternative to UROCIT-K.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A COMPARISON BETWEEN TWO POTASSIUM CITRATE REGIMENS FOR THE TREATMENT OF NEPHROLITHIASIS]. Drori, T., Abu-Ghanem, Y., Kleinmann, N., et al.[2020]

Kidney stones affect 2-3% of people in western countries, with high recurrence rates of 20-50% over ten years, highlighting the need for effective treatment options.

Three new drugs show promise in treating kidney stones: Calcibind for calcium stones linked to hypercalciuria, Lithostat as an adjunct for struvite stones, and Urocit for calcium oxalate and uric acid stones, demonstrating targeted approaches to management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New drug therapy for kidney stones: a review of cellulose sodium phosphate, acetohydroxamic acid, and potassium citrate. Lake, KD., Brown, DC.[2019]

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]

Urocit-K, a slow-releasing potassium citrate preparation, effectively increases urinary pH, potassium, and citrate levels in patients with low citrate levels, which may help prevent urinary stone formation.

The study involved 30 participants (20 patients with hypocitraturia and 10 normal volunteers) and found no significant side effects, indicating that Urocit-K is a safe and effective option for preventing stone recurrence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical study of Urocit-K: a slow releasing potassium citrate]. Hwang, TI., Yang, CR., Lai, LH.[2015]

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]

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]

References

1. India pubmed.ncbi.nlm.nih.gov

Evaluating the effectiveness of adding magnesium chloride to conventional protocol of citrate alkali therapy on kidney stone size. [2020]

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

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

3. Israel pubmed.ncbi.nlm.nih.gov

[A COMPARISON BETWEEN TWO POTASSIUM CITRATE REGIMENS FOR THE TREATMENT OF NEPHROLITHIASIS]. [2020]

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

New drug therapy for kidney stones: a review of cellulose sodium phosphate, acetohydroxamic acid, and potassium citrate. [2019]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Citrate and renal calculi. [2013]

6. China (Republic : 1949- ) pubmed.ncbi.nlm.nih.gov

[Clinical study of Urocit-K: a slow releasing potassium citrate]. [2015]

7. Poland pubmed.ncbi.nlm.nih.gov

[Therapeutic use of potassium citrate]. [2022]

8. Netherlands 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. [2022]