Abnormal heart geometry is common among patients receiving dialysis and contributes to the high annual mortality rate of 15-20%. The Frequent Hemodialysis Network aims to test in a randomized fashion if more frequent dialysis (both in the form of nightly dialysis and short daily dialysis) will improve our patients? heart geometry and their subjective view of their physical health. In combination of the Alberta Kidney Disease Network, our research team has access to stored serum samples from 243 patients who participated in the Frequent Hemodialysis Network and the Alberta Kidney Disease Network Trials. The present research application will examine stored blood samples from these participants to analyse the effect(s) of frequent dialysis versus standard dialysis on a panel of substances in the blood (known as biomarkers), which are linked with the development of abnormal heart geometry. In order to gain further understanding of the biology behind the impact of frequent dialysis versus standard dialysis on heart development, we will also examine if cells derived from rat hearts will change the expression of specific genes after exposing these cells to serum samples of patients who have either improvement or deterioration of heart geometry during the Frequent Hemodialysis Network or Alberta Kidney Disease Network Trials. The present application therefore has two specific aims:
Aim 1 : We will investigate the blood levels of biomarkers in participants of the Frequent Hemodialysis Network and Alberta Kidney Disease Network Trials in relation to the type of dialysis (frequent versus standard) assigned and their changes of heart geometry.
Aim 2 : We will examine if cells derived from rat hearts will express different genes after exposure to serum from patients whose heart geometry progressed and from patients whose heart geometry improved during the Frequent Hemodialysis Network or Alberta Kidney Disease Network Trials. Our research team has the largest collection of biological samples derived from participants of intensive hemodialysis trials worldwide. We have assembled the necessary clinical and scientific expertise to complete the proposed study aims. The results from this ancillary study proposal will provide unique biological insights into the mechanisms and potential therapeutic targets to improve the health of patients receiving dialysis in North America.

Public Health Relevance

This application is made in response to announcement PAR-09-247 ?Ancillary studies to Major Ongoing Clinical Research Studies?. The goals of this area and specific announcement are to use existing data from either the NIDDK repository, which consists of serum and plasma samples collected from NIDDK sponsored clinical trials as well as data collected in these trials or from the USRDS or UDA to perform additional analyses. We are proposing to use serum and plasma samples in the NIDDK repository that have been banked for the Frequent Hemodialysis Network Daily and Nocturnal trials to determine if the levels of biomarkers and genes expression associated with changes in heart geometry in hemodialysis patients are altered by more frequent hemodialysis therapies. These biomarker measures will complement the array of secondary outcomes that are being measured in these two clinical trials and thus should provide important data on the potential for more frequent hemodialysis therapies to improve morbidity and mortality in chronic dialysis patients.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK091288-02
Application #
8331965
Study Section
Special Emphasis Panel (ZDK1-GRB-C (J1))
Program Officer
Narva, Andrew
Project Start
2011-09-20
Project End
2014-08-31
Budget Start
2012-09-01
Budget End
2014-08-31
Support Year
2
Fiscal Year
2012
Total Cost
$253,464
Indirect Cost
$3,644
Name
University Health Network
Department
Type
DUNS #
208469486
City
Toronto
State
ON
Country
Canada
Zip Code
M5 2-M9