Endothelial Microparticles: A Novel Marker of Vascular Dysfunction

Study Overview
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Brief Summary
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The primary hypothesis of this proposal is that chronic kidney disease (CKD) and treatment with calcineurin inhibitors (CNIs) are each associated with the release of endothelial microparticles into the plasma.

Detailed Description
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The primary hypothesis of this proposal is that chronic kidney disease (CKD) and treatment with calcineurin inhibitors (CNIs) are each associated with the release of endothelial microparticles into the plasma. These injury-associated microparticles have a different molecular/protein composition than those released from endothelial cells in healthy patients, and their abundance correlates with vascular injury. To test this hypothesis the investigators propose a 3 arm case-controlled study including normal controls, individuals with stage III and IV CKD not receiving CNI therapy, and individuals with stage III and IV CKD post kidney transplantation receiving a CNI. The goal of this study is to measure the amount of microparticles in patients with kidney disease who have had a kidney transplant. Another goal of this study is to see if the measurements of microparticles are related to poor function of the vessels (endothelial dysfunction).

Official Title
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Endothelial Microparticles: A Novel Marker of Vascular Dysfunction

Conditions
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Chronic Kidney Disease

Intervention / Treatment
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* Other: Flow-mediated dilation
* Other: single blood draw


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For Healthy controls: BMI less than 40 kg/m^2 Able to give informed consent For Stage III or IV CKD patients: BMI less than 40 kg/m^2 Able to give informed consent An estimated Glomerular-Filtration Rate (GFR) of 20-60 mL/min/1.73m^2 For Post-kidney transplant and stage III or IV CKD patients: BMI less than 40 kg/m^2 Able to give informed consent An estimated Glomerular-Filtration Rate (GFR) of 20-60 mL/min/1.73m^2 Exclusion Criteria: For Healthy controls: -Women pregnant or breastfeeding For Stage III or IV CKD patients: Women pregnant or breastfeeding Adults with a life expectancy of less than one year A history of significant liver disease or congestive heart failure Hospitalization within the last three months Active infection on antibiotic therapy Uncontrolled hypertension (>140/90) Immunosuppressive therapy within the last year For Post-transplant stage III or IV CKD patients: Women pregnant or breastfeeding Adults with a life expectancy of less than one year A history of significant liver disease or congestive heart failure Hospitalization within the last three months Active infection on antibiotic therapy Uncontrolled hypertension (>140/90)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Healthy control<br>Healthy control that meets inclusion/exclusion criteria. Single blood draw and flow-mediated dilation (FMD). | Other: Flow-mediated dilation<br>* Flow-mediated dilation used to measure vascular function. The test is minimally invasive, with only a slight discomfort due to the inflation of the arm cuff.<br>Other: single blood draw<br>* single blood draw of approximately 45 mL.<br>|
| Stage III or IV CKD patients<br>Stage III or IV CKD patients that meets inclusion/exclusion criteria. Single blood draw and flow-mediated dilation (FMD). | Other: Flow-mediated dilation<br>* Flow-mediated dilation used to measure vascular function. The test is minimally invasive, with only a slight discomfort due to the inflation of the arm cuff.<br>Other: single blood draw<br>* single blood draw of approximately 45 mL.<br>|
| Post-transplant patients<br>Stage III or IV CKD Post-transplant patients that meets inclusion/exclusion criteria. Single blood draw and flow-mediated dilation (FMD). | Other: Flow-mediated dilation<br>* Flow-mediated dilation used to measure vascular function. The test is minimally invasive, with only a slight discomfort due to the inflation of the arm cuff.<br>Other: single blood draw<br>* single blood draw of approximately 45 mL.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Vascular Function | This will be measured with flow-mediated dilation and evaluate percent change from baseline over minutes. | percent change from baseline over 2 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Characterization of Microparticle source from blood analysis | A single blood draw to distinguish micro particle source characterization based upon protein, lipid and cholesterol composition. | Single time point |