Effects of Potassium Citrate in Urine of Children With Elevated Calcium in Urine and Kidney Stones

November 3, 2020 updated by: Children's Mercy Hospital Kansas City

Urinary Chemistry and Acid-Base Effects of Potassium Citrate in Children With Idiopathic Hypercalciuria and Urolithiasis

High amounts of calcium in the urine (hypercalciuria) can cause development of kidney stones in children. Treatment for these children includes plenty of fluids, a low-salt diet and medications such as potassium citrate. A major advantage of potassium citrate, as compared to hydrochlorothiazide, is its lack of side effects. One problem the researchers and others have observed is that some children continue to form kidney stones despite correction of hypercalciuria with potassium citrate. One possible explanation is that in some individuals potassium citrate therapy results in an excessive elevation of urine pH, a situation that may predispose to calcium phosphate stone formation. In this study, the researchers will study the effects of potassium citrate on urine chemistries and acid-base balance in three groups of children aged 5-17 years:

  • children who are hypercalciuric stone formers;
  • healthy children without a history of hypercalciuria or kidney stones.

Particular attention will be paid to try to identify those who develop a very high urine pH (>8) and the factors leading to this metabolic reaction.

The researchers will try to learn whether it is the child's characteristics, the disease manifestations, the dose of the drug, or a combination of the above which may be the cause of the development of very alkaline urine. Based on the results, the researchers hope to be able to better "tailor" the individual treatment for each child with kidney stones.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

Hypercalciuria is a common clinical pediatric problem that in some children is associated with renal stones. Most renal stones (80%) are formed by calcium oxalate, calcium phosphate phases (apatite), and brushite (calcium monohydrogen phosphate). Hypercalciuria can be either primary (accounts for the vast majority of children with calcium stones) or secondary. Treatment for children with calcium stones involves non-pharmacological and pharmacological interventions. Non-pharmacological interventions include high fluid intake, low sodium, and potassium enhanced diet, with RDA calcium and protein. Historically, the specific treatment for hypercalciuric stone formers has included thiazides, which reduce calciuria, lower the urinary saturation of calcium oxalate and phosphate, and restore normal intestinal calcium absorption. However thiazides induce hypokalemia and hypocitraturia, and the latter attenuates the beneficial effects of the drug on stone formation. Currently, the drug of choice replacing thiazides in treating idiopathic hypercalciuria is potassium citrate. Potassium citrate is readily absorbed from the gastrointestinal tract, and after being excreted in the urine, it inhibits the crystallization of stone forming calcium salts by binding the calcium ion, thus decreasing its urinary saturation and inhibiting the nucleation and crystal growth of calcium oxalate; therefore, potassium citrate is an effective stone inhibitor agent. A major advantage of potassium citrate is its lack of side effects. One of the problems seen in clinical practice is that some children with primary hypercalciuria, even after the calciuria is treated successfully with potassium citrate, continue to develop stones. It has been suggested that an elevation in urine pH, seen in some patients treated with potassium citrate, may result in an alkaline urinary milieu which promotes calcium phosphate stone formation. In this study, the researchers plan to investigate the effects of potassium citrate on urine chemistries and acid-base balance in children who are hypercalciuric stone formers. The researchers will try to identify whether the beneficial effects of potassium citrate supplementation on lowering urine calcium and increasing citrate might be offset by too high urine pH (>8) which could promote the formation of calcium phosphate stones. Three groups of subjects aged 5-17 years will be studied: group 1 - idiopathic hypercalciuric stone formers; group 2 - idiopathic hypercalciuric non-stone formers; and group 3 - normocalciuric subjects. Three visits will be scheduled for each participant, and the subjects will receive two doses of potassium citrate. Urine chemistries and acid-base parameters will be measured. The researchers will try to learn whether it is the child's characteristics, the disease manifestations, the dose of the drug, or a combination of the above which may be the cause of the development of very alkaline urine. Based on the study results, the researchers hope to be able to better "tailor" the individual treatment for each child with kidney stones due to idiopathic hypercalciuria.

Study Type

Interventional

Phase

  • Not Applicable

Contacts and Locations

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

Study Locations

  • United States
    • Missouri
      • Kansas City, Missouri, United States, 64108
        • The Children's Mercy Hospital

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

5 years to 17 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Children aged 5-17 years with idiopathic hypercalciuria who have history of kidney stones.
  • Healthy children aged 5-17 years without a history of hypercalciuria or kidney stones.

Exclusion Criteria:

  • Children with urolithiasis secondary to metabolic disorders unrelated to hypercalciuria (e.g. oxaluria, hypocitraturia, cystinuria), or due to secondary causes of calciuria (hypercalcemia, hyperparathyroidism, corticosteroids, furosemide).
  • Children with renal insufficiency, active urinary tract infection, hyperkalemia, gastrointestinal diseases, heart failure.
  • Children who receive angiotensin-converting enzyme inhibitors, anticholinergic medications or digitalis.
  • Children who cannot safely stop receiving the prohibited concomitant medications due to other underlying medical conditions

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: Diagnostic
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Changes in urine pH, citrate, calcium and bicarbonate after treatment with increasing doses of potassium citrate
Time Frame: Duration of protocol
Duration of protocol

Collaborators and Investigators

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

Sponsor

Children's Mercy Hospital Kansas City

Investigators

  • Principal Investigator: Ari Auron, MD, Children's Mercy Hospital Kansas City

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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

July 1, 2005

Study Completion (Actual)

May 1, 2007

Study Registration Dates

First Submitted

July 12, 2005

First Submitted That Met QC Criteria

July 18, 2005

First Posted (Estimate)

July 19, 2005

Study Record Updates

Last Update Posted (Actual)

November 5, 2020

Last Update Submitted That Met QC Criteria

November 3, 2020

Last Verified

November 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RG#05036

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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