Cardiovascular Disease, Chronic Kidney Disease
Conditions
Brief summary
There is currently little understanding of macrophage cholesterol homeostasis and foam cell formation across the spectrum of CKD. We hypothesize that an inverse relationship exist between the severity of CKD and processes underlying foam cell formation, and that the relationship becomes independent of serum lipoprotein levels as renal function declines. We propose to systematically examine scavenger receptors and cholesterol uptake as well as cholesterol transporters and efflux mechanisms in individuals with normal renal function, patients with moderate CKD. We further propose to determine if processed contributing to foam cell formation are related to the plasma lipid profile and if the relationship is modified by co-morbidities, such as diabetes, obesity, systemic inflammation which are common in this population and directly influence vascular integrity. These data will be critically important to understand when the abnormality starts and will provide crucial information.
Interventions
None listed
Sponsors
Merck Sharp & Dohme LLC
Vanderbilt University Medical Center
Study design
Observational model
CASE_ONLY
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Patients with moderate degree of CKD, or patients with advanced CKD or control subjects with intact kidney function Male or female All ethnic groups ≥ 18 years and have signed informed consent
Exclusion criteria
Pregnancy and current smoking BMI \> 45 Rheumatoid arthritis and systemic lupus erythematosus History of active or chronic hepatitis B, history of active or chronic hepatitis C, human immunodeficiency virus (HIV) For moderate CKD subjects: nephrotic syndrome For control subjects: nephrotic syndrome, patients with estimated GFR \< 60 mL/min/1.73 m\^2, or proteinuria
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| In Vitro Lipoprotein Functions | Once, at enrollment | Cholesterol efflux. Baseline and outcome measurements are the same. The cholesterol efflux was measured once using HDL isolated from CKD and control patients. There was no intervention,this assessment was performed once in each group. The measurement of cholesterol efflux is performed by an in vitro assay in cultured cells. Cells are loaded with cholesterol and maintained for 72 hours. The media of the cultured cells is then changed and the new media contains HDL from CKD or control patients. In additional cells, no HDL is added. The cells are maintained for 24 hours, and intracellular cholesterol is assessed. The cholesterol efflux represents the amount of cholesterol that was leached by HDL from each of our study groups. Thus, cells not exposed to any HDL will contain the highest intracellular cholesterol content. The amount of cholesterol in cells exposed to CKD HDL or control HDL reflects the efflux capacity of that HDL. This is expressed as percent of cholesterol removed by HDL. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| CKD Not on Dialysis Patients with CKD not on dialysis (CKD III-IV) | 72 |
| Controls Controls with normal kidney function (Control) | 31 |
| Total | 103 |
Baseline characteristics
| Characteristic | CKD Not on Dialysis | Controls | Total |
|---|---|---|---|
| Age, Continuous | 61.9 years STANDARD_DEVIATION 13.5 | 49.9 years STANDARD_DEVIATION 10.6 | 55.9 years STANDARD_DEVIATION 12 |
| HDL Function | 20.8 Percentage | 26.5 Percentage | 23.65 Percentage |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 15 Participants | 1 Participants | 16 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 56 Participants | 29 Participants | 85 Participants |
| Region of Enrollment United States | 72 participants | 31 participants | 103 participants |
| Sex: Female, Male Female | 32 Participants | 20 Participants | 52 Participants |
| Sex: Female, Male Male | 40 Participants | 11 Participants | 51 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 72 | 0 / 31 |
| other Total, other adverse events | 0 / 72 | 0 / 31 |
| serious Total, serious adverse events | 0 / 72 | 0 / 31 |
Outcome results
Primary
In Vitro Lipoprotein Functions
Cholesterol efflux. Baseline and outcome measurements are the same. The cholesterol efflux was measured once using HDL isolated from CKD and control patients. There was no intervention,this assessment was performed once in each group. The measurement of cholesterol efflux is performed by an in vitro assay in cultured cells. Cells are loaded with cholesterol and maintained for 72 hours. The media of the cultured cells is then changed and the new media contains HDL from CKD or control patients. In additional cells, no HDL is added. The cells are maintained for 24 hours, and intracellular cholesterol is assessed. The cholesterol efflux represents the amount of cholesterol that was leached by HDL from each of our study groups. Thus, cells not exposed to any HDL will contain the highest intracellular cholesterol content. The amount of cholesterol in cells exposed to CKD HDL or control HDL reflects the efflux capacity of that HDL. This is expressed as percent of cholesterol removed by HDL.
Time frame: Once, at enrollment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CKD Not on Dialysis | In Vitro Lipoprotein Functions | 20.8 Percentage of cholesterol content |
| Controls | In Vitro Lipoprotein Functions | 26.5 Percentage of cholesterol content |