Effect of Citrate Dialysate on Vascular Calcification

April 15, 2026 updated by: Charles O'Neill, Emory University
The goal of this study is to determine whether hemodialysis with citrate slows the progression of vascular calcification. Participants will be dialyzed with one of two standard dialysis solutions, one with and one without citrate, for 12 months and then switched to the other solution for 12 months. Vascular calcification will be measured on mammograms that will be performed at 6-month intervals and additional blood samples will be obtained at 6-month intervals.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Vascular calcification is a significant problem in dialysis patients that leads to poor outcomes. Currently there is no therapy that directly addresses this problem. Some of the dialysis solutions (dialysates) currently in use contain citrate, a potent inhibitor of calcium precipitation. In particular, citrate can bind to nascent hydroxyapatite crystals and prevent their propagation. Blood citrate levels are greater after dialysis with citrate dialysates than with non-citrate dialysates, which could slow vascular calcification. However, this has never been investigated. Prior research has shown that arterial calcification can be easily detected and reliably measured on routine digital mammograms, with sufficient sensitivity to follow progression. Mammography is more sensitive in detecting arterial calcification than other imaging and associated with far less radiation and cost. This will allow the researchers to detect differences between citrate and non-citrate dialysates in a safe and convenient way. Participants will be dialyzed with one of two standard dialysis solutions, one with and one without citrate, for 12 months and then switched to the other solution for 12 months. Vascular calcification will be measured by mammography every 6 months. The endpoint will be the difference in the rate of progression of breast arterial calcification (BAC) between dialysis with citrate and non-citrate dialysates.

Study Type

Interventional

Enrollment (Actual)

54

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
    • Georgia
      • Atlanta, Georgia, United States, 30318
        • Emory Dialysis at Northside
      • Atlanta, Georgia, United States, 30331
        • Emory Dialysis at Greenbriar
      • Decatur, Georgia, United States, 30033
        • Emory Dialysis at North Decatur
      • Decatur, Georgia, United States, 30034
        • Emory Dialysis at Candler

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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • hemodialysis patients with BAC on mammograms

Exclusion Criteria:

  • current warfarin use
  • severe hyperparathyroidism (likely to undergo parathyroidectomy in the next 2 years)
  • difficulty controlling serum calcium (likely to require changes in dialysate calcium concentration in the next 2 years)
  • life expectancy < 2 years
  • prisoners
  • inability to give consent

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: Supportive Care
  • Allocation: Non-Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Citrate Dialysate then Standard Dialysate
Participants receiving hemodialysis using a citrate acid concentrate dialysate for the first year of the study, then receiving hemodialysis using a non-citrate acid concentrate dialysate (standard dialysate) for the second year of the study.
Device: Citrate Dialysate
Dialysate is generated during dialysate from two concentrates (acid concentrate and bicarbonate concentrate) mixed with treated water. When used, citrate is provided in the acid concentrate. The acid concentrate with citrate is approved for this use by the FDA and will be used according to standard procedures without altered dialysis machine settings.
Other Names:
  • Citrasate
Device: Standard Dialysate
Dialysate is generated during dialysate from two concentrates (acid concentrate and bicarbonate concentrate) mixed with treated water. The acid concentrate without citrate is approved for this use by the FDA and will be used according to standard procedures without altered dialysis machine settings.
Other Names:
  • Naturalyte
Active Comparator: Standard Dialysate then Citrate Dialysate
Participants receiving hemodialysis using a non-citrate acid concentrate dialysate for the first year of the study, then receiving hemodialysis using a citrate acid concentrate dialysate for the second year of the study.
Device: Citrate Dialysate
Dialysate is generated during dialysate from two concentrates (acid concentrate and bicarbonate concentrate) mixed with treated water. When used, citrate is provided in the acid concentrate. The acid concentrate with citrate is approved for this use by the FDA and will be used according to standard procedures without altered dialysis machine settings.
Other Names:
  • Citrasate
Device: Standard Dialysate
Dialysate is generated during dialysate from two concentrates (acid concentrate and bicarbonate concentrate) mixed with treated water. The acid concentrate without citrate is approved for this use by the FDA and will be used according to standard procedures without altered dialysis machine settings.
Other Names:
  • Naturalyte

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Length of Calcified Artery Segments
Time Frame: 3 measurements during 12 months of treatment for each study period (up to 24 months for both years of the study)
Rate of progression of breast arterial calcification (BAC) is calculated by linear regression of 3 mammograms over one year in each treatment arm (Months 0, 6 and 12 versus Months 12, 18 and 24). Progression of calcification is quantified as the length of calcified artery segments per year, measured in millimeters. Slower progression of vascular calcification, indicated by lower values, is a desirable outcome.
3 measurements during 12 months of treatment for each study period (up to 24 months for both years of the study)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Serum Ionized Calcium (iCa)
Time Frame: Pre-HD and Post-HD during each study period (up to 24 months for both years of the study)
Blood samples were drawn to assess mineral metabolism prior to hemodialysis (HD) and after HD. The values are the mean milligrams (mg) of ionized calcium per deciliter (dL) of blood from two measurements during each study period.
Pre-HD and Post-HD during each study period (up to 24 months for both years of the study)
Serum Magnesium (Mg)
Time Frame: Pre-HD and Post-HD during each study period (up to 24 months for both years of the study)
Blood samples were drawn to assess mineral metabolism prior to and after hemodialysis (HD). The values are mean milligrams (mg) of magnesium per deciliter (dL) of blood from two measurements during each study period.
Pre-HD and Post-HD during each study period (up to 24 months for both years of the study)
Plasma Citrate
Time Frame: Pre-HD and Post-HD during each study period (up to 24 months for both years of the study)
Blood samples were drawn to assess mineral metabolism prior to hemodialysis (HD) and after HD. The values are the mean from two measurements during each study period.
Pre-HD and Post-HD during each study period (up to 24 months for both years of the study)

Collaborators and Investigators

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

Sponsor

Emory University

Collaborators

Fresenius Medical Care Renal Therapies Group (FMCRTG)

Investigators

  • Principal Investigator: W. Charles O'Neill, MD, Emory University

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 (Actual)

May 27, 2021

Primary Completion (Actual)

March 18, 2025

Study Completion (Actual)

March 18, 2025

Study Registration Dates

First Submitted

June 30, 2021

First Submitted That Met QC Criteria

June 30, 2021

First Posted (Actual)

July 9, 2021

Study Record Updates

Last Update Posted (Actual)

May 5, 2026

Last Update Submitted That Met QC Criteria

April 15, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STUDY00002119

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

De-identified individual participant data collected during this trial may be made available for sharing with other researchers.

IPD Sharing Time Frame

Sharing will begin after publication of results from this study.

IPD Sharing Access Criteria

Individual participant data will be made available to researchers who provide a methodologically sound proposal in order to achieve aims in the approved proposal. Proposals should be directed to Dr. O'Neill at woneill@emory.edu.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

No

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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