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

Completed

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.

Recruitment & Eligibility

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

Primary Outcome Measures

Name	Time	Method
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.

Secondary Outcome Measures