Study of the Relationship Between Body Composition, Insulin Resistance and HDL Levels

The Independent Effect of Level of Kidney Function and Body Composition On Establishing HDL Cholesterol Levels

Approximately 20 million people in the United States have some form of kidney failure. People with kidney failure have an increased chance of having low levels of high density lipid (HDL), so called "good cholesterol." Patients who are overweight or obese also have low levels of HDL. The investigators are trying to find out whether causes of low HDL are the same in people who are overweight and in patients with kidney failure so that in the future doctors can better treat low HDL cholesterol levels. People with low levels of HDL are more likely to have heart attacks and strokes and are more likely to lose kidney function. This study hope to learn more about how kidney failure causes low HDL cholesterol levels.

Study Overview

• Status: Terminated
• Conditions: Obesity; Insulin Resistance
• Intervention / Treatment: Drug: Heparin

Detailed Description

This study is not a treatment or outcome trial.This is a single center cross sectional analysis of body composition and lipoprotein level and structure among patients with graded levels of renal failure in comparison to control subjects. To study the relationship between HDL cholesterol and both body composition and insulin resistance measured as homeostatic model assessment (HOMA) among a cohort of non diabetic non-proteinuric patients with advanced chronic kidney disease (CKD) compared to non diabetic subjects having normal kidney function. Renal patients chosen will be with advanced CKD stage 3, Stage 4, and stage 5 - which is end stage renal failure (ESRD) and on hemodialysis. Fasting blood will be taken for the evaluation of baseline lipid and renal function, and blood glucose level to make sure that there is no recent evidence of diabetes. Body compositions will be measured with 2 established methods: DEXA and whole body bio-impedance spectroscopy (BIS). Fat mass and analysis will be estimated so as to provide a relationship between adiposity, insulin resistance, residual renal function and HDL levels and structure.

• Study Type: Observational
• Enrollment (Actual): 50

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

This is a single center cross sectional study of renal failure in comparison to control subjects. This is not a treatment or outcome trial.

Description

Inclusion Criteria:

• self report of stable body weight during the past six months;
• BMI 18-40 kg/m2; Hemodialysis dependent for at least 3 months, prevalent ESRD (end stage renal disease) cohort;
• GFR > 15 < 44 ml/min (CKD cohort);
• GFR > 60 ml/min (Control cohort).

Exclusion Criteria:

• Diabetes Mellitus (American Diabetes Association definition: fasting glucose >120 mg/dl);
• Evidence of liver disorder, ie; hepatitis
• Evidence of thyroid disorders
• HIV by medical history (HIV test will not be performed)
• Renal transplant recipient
• Oral contraceptive/ hormone replacement therapy
• Systemic use of systemic or inhaled corticosteroids in the past month
• Contraindication to systemic anticoagulation (heparin administration is necessary to measure levels of LPL, HL);
• Hemoglobin < 8.5 g/dl (anemia);
• Current, within 2 months use of any hypolipidemic or anti-diabetic agents;
• Patients treated with a fibric acid derivative or niacin in the past 4 weeks;
• Urinary protein excretion of greater than 0.5 grams per day;
• Any other condition that, in the opinion of the investigators, would put the subject at risk.

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
control; heparin at 50unit/kg of body weight having glomerular filtration rate (GFR) of greater than 60	Drug: Heparin; This is not an interventional study. The investigators use heparin at 50unit/kg of body weight to release enzyme lipoprotein lipase (LPL) from the body. LPL level will be used as part of calculation of lipid analysis and measurements; Other Names: Heparin Sodium
chronic renal disease (CKD3b); heparin at 50unit/kg of body weight having glomerular filtration rate (GFR) of 30-45	Drug: Heparin; This is not an interventional study. The investigators use heparin at 50unit/kg of body weight to release enzyme lipoprotein lipase (LPL) from the body. LPL level will be used as part of calculation of lipid analysis and measurements; Other Names: Heparin Sodium
chronic renal disease (CKD4); heparin at 50unit/kg of body weight having glomerular filtration rate (GFR) of 15-30	Drug: Heparin; This is not an interventional study. The investigators use heparin at 50unit/kg of body weight to release enzyme lipoprotein lipase (LPL) from the body. LPL level will be used as part of calculation of lipid analysis and measurements; Other Names: Heparin Sodium
chronic renal disease (CKD5); heparin at 50unit/kg of body weight having glomerular filtration rate (GFR) of less than 15, or on hemodialysis	Drug: Heparin; This is not an interventional study. The investigators use heparin at 50unit/kg of body weight to release enzyme lipoprotein lipase (LPL) from the body. LPL level will be used as part of calculation of lipid analysis and measurements; Other Names: Heparin Sodium

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HDL (High Density Lipoprotein) Level in Control and Chronic Kidney Disease (CKD 3b, 4, 5) Groups	HDL (high-density lipoprotein), is called "good" cholesterol. It binds to cholesterols marked for disposal back to the liver to be digested and disposed by the body. High HDL level may lower your risk for heart disease and stroke.	HDL (high density lipoprotein) (mg/dL) -- this is a cross sectional study; only one measurement collected, termed "baseline"
LDL Level in Control and Chronic Kidney Disease (CKD3b, CKD4, CKD5) Groups	LDL (low-density lipoprotein), is a type of cholesterol (fat) circulating in the blood vessels, and can form plaques. High levels of LDL cholesterol may raise your risk for heart disease and stroke.	This is a cross sectional study; only one measurement collected, termed "baseline"
C Reactive Protein (CRP) Level in Control and Chronic Kidney Disease (CKD3b, CKD4, CKD5) Groups	C-reactive protein (CRP) is an inflammation marker produced by the liver. An increase in CRP value may means inflammation in the body.	This is a cross sectional study; only one measurement collected, termed "baseline"
Body Mass Index (BMI) in Control and Chronic Kidney Disease (CKD3b, CKD4, CKD5) Groups	Body Mass Index (BMI) is calculated from subject's weight (kilogram) and height (meter)	This is a cross sectional study; only one measurement collected, termed "baseline"
Insulin Level in Control and Chronic Kidney Disease (CKD3b, CKD4, CKD5) Groups	Insulin is a hormone made by the pancreas that allows the body to use or store sugar (glucose) from the food eaten. Insulin regulates blood sugar level.	This is a cross sectional study; only one measurement collected, termed "baseline"
LCAT Activity (Lecithin-Cholesterol Acyltransferase) in Control and Chronic Kidney Disease Groups, Mainly to CKD3b, CKD4	LCAT measures phospholipase activity in plasma. Measuring LCAT activity may be useful in clarifying the aspects of lipid metabolism in relation to reverse cholesterol transport No data collected- no standard deviation calculated	This is a cross sectional study; only one measurement collected, termed "baseline"
CETP Activity (Lecithin-Cholesterol Acyltransferase) in Control and Chronic Kidney Disease Groups, Mainly to CKD3b, CKD4	CETP activity measures the transfers of neutral lipids from high density lipoproteins (HDL) to very low density lipoprotein (VLDL) and low density lipoprotein (LDL). CETP may give us the other clue to lipoprotein metabolism and reverse cholesterol transport pathway No data collected- no standard deviation calculated	This is a cross sectional study; only one measurement collected, termed "baseline"

Collaborators and Investigators

• Sponsor: University of California, Davis
• Collaborators: Dialysis Clinic, Inc.
• Investigators: Principal Investigator: George A Kaysen, MD PhD, University of California, Davis; Study Director: Tjien Dwyer, BS, University of California, Davis

Publications and helpful links

General Publications

• Molfino A, Don BR, Kaysen GA. Comparison of bioimpedance and dual-energy x-ray absorptiometry for measurement of fat mass in hemodialysis patients. Nephron Clin Pract. 2012;122(3-4):127-33. doi: 10.1159/000350817. Epub 2013 May 9.

Helpful Links

• Nephron Clin Pract. 2012; 122(0): 127-133.

Study record dates

Study Major Dates

• Study Start (Actual): October 22, 2008
• Primary Completion (Actual): February 28, 2019
• Study Completion (Actual): February 28, 2019

Study Registration Dates

• First Submitted: March 10, 2016
• First Submitted That Met QC Criteria: April 28, 2016
• First Posted (Estimate): April 29, 2016

Study Record Updates

• Last Update Posted (Actual): February 23, 2021
• Last Update Submitted That Met QC Criteria: February 19, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: obesity; insulin resistance; lipid; high density lipoprotein (HDL); glomerular filtration rate (GFR)
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hyperinsulinism; Insulin Resistance; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Heparin; Calcium heparin
• Other Study ID Numbers: 220939

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: once published; data will be shared
• IPD Sharing Time Frame: once published; data will be shared
• IPD Sharing Access Criteria: once published; data will be shared
• IPD Sharing Supporting Information Type: SAP; ICF

Study Data/Documents

1. Informed Consent Form
   Information comments: for a copy of Approved Consent Form-please contact Study Coordinator -Tjien Dwyer at tlthio@ucdavis.edu

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No