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

Study Description

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

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.

Condition or disease
Chronic Kidney Disease; Cardiovascular Disease

Study Design

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Study Type :	Observational
Actual Enrollment :	103 participants
Observational Model:	Case-Only
Time Perspective:	Retrospective
Official Title:	Mechanisms of CKD-Induced Foam Cell Formation
Study Start Date :	February 2013
Actual Primary Completion Date :	April 2015
Actual Study Completion Date :	April 2015

Groups and Cohorts

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

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

Outcome Measures

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Primary Outcome Measures :

1. In Vitro Lipoprotein Functions [ Time Frame: 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.

Eligibility Criteria

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No
Sampling Method:	Probability Sample

Study Population

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

Controls with normal kidney function (Control)

Criteria

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

Contacts and Locations

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

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

Sponsors and Collaborators

Vanderbilt University Medical Center

Merck Sharp & Dohme Corp.

Investigators

Principal Investigator:	Valentina Kon, MD	Vanderbilt University Medical Center

More Information

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Valentina Kon, Principal Investigator, Vanderbilt University
ClinicalTrials.gov Identifier:	NCT01671605 History of Changes
Other Study ID Numbers:	090846
First Posted:	August 23, 2012
Results First Posted:	April 21, 2017
Last Update Posted:	April 21, 2017
Last Verified:	March 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

Additional relevant MeSH terms:

Cardiovascular Diseases; Kidney Diseases; Renal Insufficiency, Chronic; Urologic Diseases; Renal Insufficiency