Role of Medication in Making Urine Less Acidic as Part of Kidney Stone Prevention

February 3, 2026 updated by: Brett Johnson, University of Texas Southwestern Medical Center

Kinetics of Urinary Alkalinization Therapy in Patients With Nephrolithiasis

Diet and medications are the cornerstones of kidney stone prevention. Potassium citrate is a commonly prescribed medication to help prevent kidney stones by making urine less acidic. There are different forms of potassium citrate such as over-the-counter tablet or powder, and slow-release tablets that require a prescription. However, it is unknown if one form is better than the others. Therefore, we want to compare different forms of potassium citrate and find out how well they work and whether patients prefer one form over the others.

The study period will last approximately 6 weeks for each participant. Patients will be instructed to take one form of potassium citrate for one week at a time followed by a washout period for one week. This process will be completed a total of three times as we seek to study the effects of three forms of potassium citrate.

At the end of each trial week patients will be asked to provide urine samples and complete two surveys. Urine will need to be collected for 24 hours, which will then be examined to determine the effects that each form of potassium citrate has on urine. In addition, completed surveys will give us information on how well the medication was tolerated and their satisfaction with the treatment. There is a possibility that patients like one form better than others, and it is also possible that they do not see a difference at all.

Throughout the duration of the study patients will be asked to be a directed diet. This will be based on general recommendations by the National Kidney Foundation for the prevention of kidney stones.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Background and Rationale

Urinary stone disease (USD) has been increasing with a recent prevalence estimate of 11% in the United States. Recurrence is common, with up to 50% of individuals experiencing another stone event within 10 years without treatment. This condition results in pain, diminished quality of life, missed work and school, as well as chronic kidney disease and renal failure, and carries significant economic implications as USD is the most expensive non-malignant urologic condition in the United States.

Diet modification and pharmacotherapy form the cornerstones of kidney stone prevention. Alkalinization of urine is commonly used to prevent kidney stone recurrence. Physiologically, urine alkalinization increases urinary pH and raises urinary citrate levels. Correction of acidic urine pH (<5.5) can counteract uric acid crystallization. Additionally, increased citrate levels are known to be a potent inhibitor of calcium stone formation by binding directly to urinary calcium and inhibiting crystal nucleation. Therefore, alkali therapy addresses risk factors for several types of kidney stones and is recommended for patients with recurrent calcium stones with or without hypocitraturia, uric acid stones, or cystine stones.

Potassium citrate is the most commonly prescribed form of alkali therapy. It is recommended by multiple national society guidelines for patients with recurrent calcium stones in whom modifiable 24-hour urine (24U) risk factors are absent, already addressed, or for those in whom dietary modification alone was ineffective. Unfortunately, the long-term compliance has been reported to be as low as 13%. Part of the problem is that potassium citrate is not well-tolerated due to its gastrointestinal side effect profile. So even if urinary alkalization is more robust with potassium citrate, the clinical effects will not be realized if patients are not compliant with the medication. Further exacerbating noncompliance is the unavailability of desirable powder forms of potassium citrate (crystal packets), or the cost of the slow-release form of potassium citrate (UroCit-K) estimated to be more than $150 per month, which may be prohibitively expensive for some patients. Additionally, the number of pills needed to be taken on a daily basis is another reason that could lead to noncompliance.

Alternative alkali therapies are available and should be considered. Over-the-counter (OTC) alkali therapy including medicinal foods and dietary supplements have been used as alternatives to traditional potassium citrate therapy for urinary alkalinization. Indeed, OTC therapies are growing in popularity, with half of recurrent stone-formers reporting utilization of alternative medicines. Moreover, the large number of available products further supports the high demand for such alternative agents. However, there is limited evidence to support their use and efficacy as the comparative efficacy, cost, and tolerability between these agents compared to the current gold standard potassium citrate therapy is unknown.

Our research group has previously studied commonly available OTC alternative alkali citrate products to determine the actual quantities of citrate and citrate as alkali in these supplements. This included powder products such as Litholyte®, Moonstone®, and NOW® Potassium citrate. Litholyte® powder was felt to provide reasonable balance between alkali citrate, cost, and ease of consumption. To build upon this work, we aim to perform an open-label Phase-1 clinical trial using Litholyte®, a dietary supplement containing potassium/magnesium citrate, and compare its metabolic effects to the gold standard potassium citrate (UroCit-K) therapy. We hypothesize that in recurrent stone formers, Litholyte® products will result in similar urinary alkalinization and urinary citrate levels compared to UroCit-K but will be better tolerated and less costly.

Study Type

Interventional

Enrollment (Estimated)

20

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • adults, 18 years or older
  • recurrent stone formers or first-time stone formers at high risk for recurrence
  • have a baseline 24-hour urine within six months from study enrollment
  • have the ability to adhere to a directed diet

Exclusion Criteria:

  • minors (age <18 years)
  • mentally incapacitated and/or unable to provide consent
  • prisoners
  • pregnant or breastfeeding individuals
  • concurrent potassium citrate therapy
  • concurrent thiazide therapy
  • chronic kidney disease (eGFR <60)
  • solitary kidney
  • unable to take any of the study medications due to a prior adverse reaction or other health-related reason (ex: severe renal impairment, hyperkalemia, or severe acidosis or alkalosis).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Urine Alkalization
In this crossover study, patients will serve as their own controls. Patients will receive slow-release potassium citrate (UroCit-K), potassium magnesium citrate (powder), or potassium magnesium citrate (tablets). The study period will last approximately 6 weeks for each participant. Patients will be instructed to take one form of potassium citrate for one week at a time followed by a washout period for one week. This process will be completed a total of three times as we seek to study the effects of three forms of potassium citrate.
Drug: Potassium Citrate Extended Release Oral Tablet
In this crossover study, patients will serve as their own controls. Patients will receive slow-release potassium citrate (UroCit-K), potassium magnesium citrate (powder), or potassium magnesium citrate (tablets). The study period will last approximately 6 weeks for each participant. Patients will be instructed to take one form of potassium citrate for one week at a time followed by a washout period for one week. This process will be completed a total of three times as we seek to study the effects of three forms of potassium citrate.
Other Names:
  • potassium magnesium citrate (powder)
  • potassium magnesium citrate (tablets)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Urinary pH
Time Frame: From enrollment to the end of treatment at 6 weeks.
Change in urinary pH and urinary citrate
From enrollment to the end of treatment at 6 weeks.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Texas Southwestern Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

July 1, 2026

Primary Completion (Estimated)

July 31, 2027

Study Completion (Estimated)

October 31, 2027

Study Registration Dates

First Submitted

January 27, 2025

First Submitted That Met QC Criteria

February 4, 2025

First Posted (Actual)

February 11, 2025

Study Record Updates

Last Update Posted (Actual)

February 5, 2026

Last Update Submitted That Met QC Criteria

February 3, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STU-2024-1257

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

This is a single center study

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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