Potassium Citrate Supplementation vs. Dietary Counseling

Kidney Stone Clinical Trial

Official title:

Does Potassium Citrate Supplementation Reduce Stone Recurrence in Calcium Phosphate Stone Formers With Risk Factors?

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01980004
• Other study ID #: 13-3010
• Status: Withdrawn
• Phase: Phase 2
• First received: November 1, 2013
• Last updated: October 7, 2015
• Start date: November 2013
• Est. completion date: August 2015

Study information

• Verified date: September 2015
• Source: University of North Carolina, Chapel Hill
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to compare the role of potassium citrate supplementation with dietary education versus dietary education alone in the reduction of stone risks and events in patients with predominantly calcium phosphate kidney stones.

Description:

The prevalence of kidney stone disease in the United States is increasing. Concurrently, an increase in calcium phosphate stone composition is also being observed. Recurrence of kidney stone disease has been reported as high as 50% at five years. Citrate supplementation is widely considered as one of the primary medical cornerstones to decrease kidney stone recurrence. Urinary citrate is a potent inhibitor of calcium stone formation by binding ionic urinary calcium as well as direct inhibition of calcium oxalate formation. Additionally, increased citrate, an alkali, raises urine pH which alters the solubility of certain stone types including uric acid and cystine stones. Potassium citrate supplementation is the primary proven approach to increasing urinary citrate and is a well-established preventive option in stone disease. However, medication treatment can cause epigastric discomfort, frequent large bowel movements and add to the patient's prescription financial burden. Dietary education including lemonade therapy provides natural dietary sources of citrate and may be an alternative to pharmacologic therapy without the associated gastrointestinal symptoms or costs.

The utility of citrate supplementation has not been previously evaluated prospectively in the calcium phosphate stone former. Calcium phosphate stone formation occurs in a more alkaline urine environment. It has been postulated that citrate supplementation could promote calcium phosphate stone occurrence due to its ability to raise urine pH despite the inhibitory effects of increasing urinary citrate. However, this finding has not been observed in limited retrospective studies. The purpose of this investigation is to prospectively evaluate the benefit of citrate supplementation either through potassium citrate treatment with dietary education vs. dietary education alone to reduce stone recurrence in calcium phosphate stone formers with risk factors.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: August 2015
• Est. primary completion date: August 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Patients = 18 years old, being seen at UNC Chapel Hill or Vanderbilt Urology Clinics

2. Documented stone analysis with = 50% calcium phosphate (hydroxyapatite and/or brushite) composition

3. 24 hour urine citrate (= 500) on initial evaluation of at least one 24-hour urine study

4. 24 hour urine pH = 6.0 on initial evaluation of at least one 24-hour urine study

Exclusion Criteria:

1. Documented stone analysis with any calcium carbonate or magnesium ammonium phosphate composition

2. Systemic cause for stone disease (primary hyperparathyroidism, complete distal renal tubular acidosis, systemic acidosis, active urinary tract infection)

3. 24 hour urine calcium/kg (> 4) or 24 hour urine calcium/Cr (>140) on initial evaluation of at least one 24-hour urine study

4. Concurrent medication therapy (potassium citrate, sodium citrate, sodium bicarbonate, diuretic, angiotensin-converting enzyme inhibitor, angiotensin II receptor antagonist, topiramate, acetazolamide)

5. Renal insufficiency (GFR = 60)

6. Elevated serum potassium level (= 4.5) or hyperkalemia

7. Low serum bicarbonate level (< 24)

8. High serum calcium level (>10)

9. Pregnancy

10. Inability to obtain informed consent

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Kidney Calculi
• Kidney Stone
• Nephrolithiasis

Intervention

Dietary Supplement:
• Potassium Citrate Supplementation
20 mEq taken twice daily

Other:
• Dietary Education
Dietary counseling will include both a verbal discussion in the clinic regarding increased fluid intake, a moderate calcium rich diet and lemonade therapy as well as receiving a written handout on these topics.

Locations

Country	Name	City	State
United States	North Carolina Memorial Hospital	Chapel Hill	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
University of North Carolina, Chapel Hill	Vanderbilt University

Country where clinical trial is conducted

United States, 

References & Publications (8)

Chow K, Dixon J, Gilpin S, Kavanagh JP, Rao PN. Citrate inhibits growth of residual fragments in an in vitro model of calcium oxalate renal stones. Kidney Int. 2004 May;65(5):1724-30. — View Citation

Mandel N, Mandel I, Fryjoff K, Rejniak T, Mandel G. Conversion of calcium oxalate to calcium phosphate with recurrent stone episodes. J Urol. 2003 Jun;169(6):2026-9. — View Citation

Parks JH, Worcester EM, Coe FL, Evan AP, Lingeman JE. Clinical implications of abundant calcium phosphate in routinely analyzed kidney stones. Kidney Int. 2004 Aug;66(2):777-85. — View Citation

Pattaras JG, Moore RG. Citrate in the management of urolithiasis. J Endourol. 1999 Nov;13(9):687-92. Review. — View Citation

Penniston KL, Steele TH, Nakada SY. Lemonade therapy increases urinary citrate and urine volumes in patients with recurrent calcium oxalate stone formation. Urology. 2007 Nov;70(5):856-60. Epub 2007 Oct 24. — View Citation

Preminger GM. Renal calculi: pathogenesis, diagnosis, and medical therapy. Semin Nephrol. 1992 Mar;12(2):200-16. Review. — View Citation

Robinson MR, Leitao VA, Haleblian GE, Scales CD Jr, Chandrashekar A, Pierre SA, Preminger GM. Impact of long-term potassium citrate therapy on urinary profiles and recurrent stone formation. J Urol. 2009 Mar;181(3):1145-50. doi: 10.1016/j.juro.2008.11.014. Epub 2009 Jan 18. — View Citation

Scales CD Jr, Smith AC, Hanley JM, Saigal CS; Urologic Diseases in America Project. Prevalence of kidney stones in the United States. Eur Urol. 2012 Jul;62(1):160-5. doi: 10.1016/j.eururo.2012.03.052. Epub 2012 Mar 31. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in 24-hour urine parameters		4-6 weeks from baseline	No