Vascular Calcification
Conditions
Keywords
Hemodialysis, Breast arterial calcification
Brief summary
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
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.
Interventions
DEVICECitrate 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.
DEVICEStandard 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.
Sponsors
Emory University
Fresenius Medical Care Renal Therapies Group (FMCRTG)
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Length of Calcified Artery Segments | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum Ionized Calcium (iCa) | 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. |
| Serum Magnesium (Mg) | 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. |
| Plasma Citrate | 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. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORW. Charles O'Neill, MD
Emory University
Participant flow
Recruitment details
The first individual gave informed consent to participate on May 27, 2021 and all study follow up was complete by March 18, 2025. Participants were enrolled from Emory Dialysis centers in Atlanta and Decatur, Georgia, USA.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 14 Participants |
| Age, Categorical Between 18 and 65 years | 40 Participants |
| Age, Continuous | 56.4 years STANDARD_DEVIATION 9.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 25 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 25 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Region of Enrollment United States | 25 Participants |
| Sex: Female, Male Female | 54 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 54 | 5 / 54 |
| other Total, other adverse events | 0 / 54 | 0 / 54 |
| serious Total, serious adverse events | 0 / 54 | 0 / 54 |
Outcome results
None listed