Whole Blood Platelet Aggregation in Chronic Kidney Disease Patients on Aspirin Study

Study ID
12CRP11830004

Cancer Related
No

Healthy Volunteers
Yes

Study Sites

  • UT Southwestern-Clinical Translational Research Center (CTRC)
  • Clements University Hospital
  • Dallas Veteran's Affairs Medical Center
  • UT Southwestern Ambulatory Services
  • Parkland Health & Hospital System

Contact
Kyle West
214/645-8290
kyle.west@utsouthwestern.edu

Principal Investigator
S Hedayati, M.D.

Official Title

Whole Blood Platelet Aggregation in Chronic Kidney Disease Patients on Aspirin

Brief Overview


Higher coronary in-stent thromboses and bleeding complications on anti-platelet agents are
more common in Chronic Kidney Disease vs. non-Chronic Kidney Disease patients. Poor
inhibition of platelet aggregation by anti-platelet agents predicts future cardiovascular
events. Clinical practice guidelines are ambiguous about the use of these agents in Chronic
Kidney Disease due to lack of controlled studies. The investigators hypothesize that
patients with Chronic Kidney Disease compared with non-Chronic Kidney Disease have reduced
platelet aggregation and poor platelet inhibitory response to aspirin. The aims are to 1)
define the range of whole blood platelet aggregation in stages 3-5 Chronic Kidney Disease
patients; 2) investigate whether patients with stages 4-5 Chronic Kidney Disease vs.
non-Chronic Kidney Disease have lower platelet aggregation or impaired von Willebrand Factor
activity; and 3) compare inhibition of platelet aggregation from baseline after 2 weeks of
aspirin therapy and another 2 weeks of clopidogrel therapy added to aspirin in Chronic
Kidney Disease vs. non-Chronic Kidney Disease patients. Accomplishing these aims will
provide pilot data to power future studies of targeted anti-platelet agent treatments in
Chronic Kidney Disease in order to improve cardiovascular outcomes.

Summary


Patients will be consented for the study and asked to initial on the consent form to state
whether they agree for the genetic testing. After signing informed consent, complete medical
history and medication list will be obtained and verified with the electronic medical
record. After meeting all inclusion and exclusion criteria during the screening visit, those
patients on aspirin for primary prevention of cardiovascular events will be asked to stop it
for 2 weeks prior to blood collection for baseline data. Normal controls will be chosen
after frequency matching for decade of age, gender, diabetes mellitus and interval of body
mass index (5 kg/m2). Dietary supplements (Vitamin E and fish oil) known to affect platelet
function will be assessed and patients on those will be asked to discontinue these.
Participants with also be asked to not eat foods known to affect platelet function (coffee,
chocolate, grapes, and alcohol) 48 hours prior to sample collection on visit 1. An
interviewer-administered assessment of diet and exercise with a modified 24-hour dietary
recall and the Stanford 7-day Physical activity Recall will be performed to ensure dietary
consistency which may affect platelet aggregability on visit 1. Blood will be drawn via
venopuncture for laboratory studies (whole blood platelet aggregation, von Willebrand Factor
antigen levels and activity). Participants will be administered aspirin 81 mg for 2 weeks
and asked to return in 2 weeks. On visit 2, whole blood platelet aggregation will be
re-measured and questionnaires filled out. Two oral swabs will be taken from those
participants who consented for genetic testing and samples will be stored at Dallas Veterans
Affairs Medical Center for short term until shipped to Diagnostics Laboratory for genetic
testing of clopidogrel cytochrome P450 polymorphisms. All participants will be administered
clopidogrel 75 mg daily on top of aspirin 81 mg for 2 weeks and asked to return in 2 weeks.
On visit 3, whole blood platelet aggregation will be re-measured and questionnaires filled
out. At the completion of the study, participants will be placed back on their original
antiplatelet agent if applicable and referred back to the primary care provider.

Participant Eligibility


Inclusion Criteria:

- Male or female >21 years

Cases:

Chronic kidney disease stages 4-5, with estimated glomerular filtration rate of <30

Controls:

estimated glomerular filtration rate of >90, urinary albumin to creatinine ratio <30 and
no other kidney damage

Exclusion Criteria:

- End-stage renal disease (peritoneal dialysis and hemodialysis)

- Kidney transplant or any other transplant patient

- Recent hospitalizations <3 months

- Acute coronary or cerebrovascular event in the last 12 months

- Surgery in the last 3 months

- Blood dyscrasias or active bleeding

- Gastro-intestinal bleeding in the last 6 months

- Concomitant use of other anti-platelet agent or antithrombotic drugs

- Recent treatment (<30 days) with a glycoprotein antagonist or proton pump inhibitor

- Hematocrit <25% or white blood cell count >20,000 or platelet count <50,000

- Any active malignancy or liver disease

- No current diagnosis of depression, not on any antidepressant medications,