Prevention Strategies for Kidney Stones

Overseen By Brianne Duncan, RN

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Vanderbilt University Medical Center

Must not be taking: Thiazides, Topiramate, others

Disqualifiers: Pregnancy, Chronic kidney disease, others

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

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

Compensation: Varies

Number of Visits: 1

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to find the best ways to prevent kidney stones. Researchers are testing two approaches: one based on personalized tests and another more general. Both involve changes in diet and medication, including potassium citrate, which helps prevent kidney stones. People who have had at least two kidney stone attacks in the past five years might be suitable candidates. The study also examines adherence to the plans and any side effects experienced. As a Phase 4 trial, this research focuses on understanding how an already FDA-approved and effective treatment can benefit more patients.

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 is the safety track record for these treatments?

Research shows that potassium citrate, used in both treatment groups, is generally well-tolerated. Studies have found that it helps prevent kidney stones by reducing urine acidity, making stone formation more difficult. Most people experience only mild side effects, such as nausea. The FDA has approved the drug for other conditions, like renal tubular acidosis, indicating its general safety. Overall, potassium citrate is considered safe for most people, with few serious side effects reported. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about the prevention strategies for kidney stones in this trial because they offer a personalized approach. Unlike standard treatments that generally involve dietary changes and medications without specific targeting, the selective therapy arm in this trial tailors diet and drug interventions based on individual 24-hour urine analysis results. This customization aims to address the unique metabolic factors contributing to kidney stone formation in each person, potentially leading to more effective prevention. Meanwhile, the empiric therapy arm tests a more traditional approach, but its comparison with the selective therapy may highlight the benefits of personalized care. This trial could pave the way for more individualized and potentially more successful prevention strategies for kidney stones.

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

Research has shown that potassium citrate can effectively prevent kidney stones. In this trial, participants will join different treatment arms to evaluate its effectiveness. Studies indicate that potassium citrate can reduce the recurrence of stones by 75% in individuals with calcium-based stones. It works by increasing citrate levels and decreasing calcium in urine, which helps prevent stone formation. Another study found that potassium-magnesium citrate also significantly reduced stone recurrence. These findings suggest that potassium citrate is a promising option for preventing kidney stones. ^{4 6 7 8 9}

Who Is on the Research Team?

Ryan Hsi, MD

Principal Investigator

Vanderbilt University Medical Center

Are You a Good Fit for This Trial?

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Empiric Therapy: Diet
• Empiric Therapy: Drug
• Selective Therapy: Diet
• Selective Therapy: Drug

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.

How Is the Trial Designed?

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

Empiric Therapy: Diet is already approved in United States, European Union for the following indications:

Approved in United States as Urocit-K for:

• Renal tubular acidosis
• Hypocitraturic calcium oxalate nephrolithiasis
• Uric acid lithiasis with or without calcium stones

Approved in European Union as Cytra-K for:

• Renal tubular acidosis
• Hypocitraturic calcium oxalate nephrolithiasis
• Uric acid lithiasis with or without calcium stones

Who Is Running the Clinical Trial?

Vanderbilt University Medical Center

Lead Sponsor

Trials

922

Recruited

939,000+

Published Research Related to This Trial

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]

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 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]

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]

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]

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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6300162/

Impact of Potassium Citrate vs. Citric Acid on Urinary Stone ... Potassium citrate may protect against calcium phosphate stones by enhancing urine citrate excretion and lowering urine calcium, but it raises urine pH.

2. journals.lww.com journals.lww.com/ebp/fulltext/2018/01000/is_potassium_citrate_effective_for_preventing.24.aspx

Is potassium citrate effective for preventing kidney stone... Potassium citrate and other potassium-containing citrate salts reduce kidney stone recurrence by 75% in patients with calcium-containing stones.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2974409/

Long-Term Treatment with Potassium Citrate and Renal ... Results: Parallel to a significant rise in urinary citrate and decreased urinary calcium (all P < 0.001), KC led to a dramatic reduction in the stone event rate ...

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. sciencedirect.com sciencedirect.com/science/article/pii/S2161831323002715

Review Kidney Stone Prevention This review provides comprehensive and up-to-date knowledge on strategies to prevent KSD. These include increased fluid intake and diuresis, lifestyle and ...

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. webmd.com webmd.com/drugs/2/drug-8836-7227/potassium-citrate-oral/potassium-citrate-tablet-oral/details

Potassium Citrate (Urocit-K) - Uses, Side Effects, and More It works by decreasing the amount of acid in the urine, which makes it harder for kidney stones to form. The most common side effects are nausea ...

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2010/019071s012lbl.pdf

drug label - accessdata.fda.gov Potassium citrate is indicated for the management of renal tubular acidosis. [see ... Prevention of Recurrent Calcium Stone Formation with Potassium Citrate.

9. racgp.org.au racgp.org.au/clinical-resources/clinical-guidelines/handi/handi-interventions/other/citrate-salts-for-preventing-kidney-stones

Citrate salts for preventing kidney stones Citrate salts can prevent about three-quarters of new stones forming. Potassium citrate is also used for the prevention of urate stones.