Effect of Citrate Dialysis on Vascular Calcification

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Effect of Citrate Dialysate on Vascular Calcification

Conditions
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Vascular Calcification

Intervention / Treatment
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* Device: Citrate Dialysate
* Device: Standard Dialysate


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Citrate Dialysate then Standard Dialysate<br>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<br>* 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.<br>* Other names: Citrasate;Device: Standard Dialysate<br>* 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.<br>* Other names: Naturalyte;|
| Active Comparator: Standard Dialysate<br>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<br>* 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.<br>* Other names: Citrasate;Device: Standard Dialysate<br>* 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.<br>* Other names: Naturalyte;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in rate of progression of breast arterial calcification (BAC) | Rate of BAC progression will be calculated by linear regression of 3 mammograms 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, measured in millimeters. | Baseline, Month 6, Month 12, Month 18, Month 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hemodialysis, Breast arterial calcification