Mechanisms of Chronic Kidney Disease (CKD)-Induced Foam Cell Formation

Mechanisms of CKD-Induced Foam Cell Formation

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.

Study Overview

• Status: Completed
• Conditions: Cardiovascular Disease; Chronic Kidney Disease

• Study Type: Observational
• Enrollment (Actual): 103

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt Outpatient Dialysis Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients with CKD not on dialysis (CKD III-IV)

Controls with normal kidney function (Control)

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Retrospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
CKD not on dialysis; Patients with CKD not on dialysis (CKD III-IV)
Controls; Controls with normal kidney function (Control)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Once, at enrollment

Collaborators and Investigators

• Sponsor: Vanderbilt University Medical Center
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Principal Investigator: Valentina Kon, MD, Vanderbilt University Medical Center

Study record dates

Study Major Dates

• Study Start: February 1, 2013
• Primary Completion (Actual): April 1, 2015
• Study Completion (Actual): April 1, 2015

Study Registration Dates

• First Submitted: August 20, 2012
• First Submitted That Met QC Criteria: August 22, 2012
• First Posted (Estimate): August 23, 2012

Study Record Updates

• Last Update Posted (Actual): April 21, 2017
• Last Update Submitted That Met QC Criteria: March 10, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Cardiovascular Diseases; Kidney Diseases; Renal Insufficiency, Chronic
• Other Study ID Numbers: 090846

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No