Persons in the US with end stage renal disease (ESRD) have an annual mortality rate of over 20% and an age-specific death rate from cardiovascular disease that is 10-100 times higher than the general population. Much of this excess mortality is due to sudden cardiac death (SCD). Surprisingly, few prospective studies have examined risk factors for SCD in ESRD patients and these studies did not measure many risk factors known to be important in the general population. In the CHOICE cohort study, we found an SCD incidence of 18% over 4 years of follow up. Our overall hypothesis is that factors that increase risk for SCD in the general population are highly prevalent in the dialysis population and are independent predictors of altered autonomic tone, impaired ventricular conduction, and SCD. We propose a prospective, longitudinal study of 1,000 incident ESRD patients treated with hemodialysis to determine the cardiovascular, dialysis-related, and genetic risk factors leading to altered autonomic tone, impaired ventricular conduction, and SCD. Participants aged 18 and older will be recruited from the Baltimore area. We anticipate that 60% of the cohort will be African American and 50% will have diabetes. Techniques developed in other successful studies of ESRD by the investigative team will be used to recruit and follow participants. Coronary calcium, vessel stenosis, and left ventricular structure and function will be assessed using computed tomography (CT) and CT angiography at baseline;ECGs, questionnaires and biological specimens will be collected at baseline and annually. Heart rate variability, measures of QT duration, and presence of ventricular late potentials will be assessed by analysis of annual ECG recordings. Cause of death will be adjudicated using standard criteria. This study will also allow identification of dialysis-related risk factors for SCD and its intermediates that are unique to ESRD, setting the stage for clinical trials to test therapies to prevent SCD in this high risk population. In addition, the proposed work will provide an infrastructure to answer, in future studies, a host of questions related to the pathogenesis of morbidity and mortality in the ESRD population.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK072367-05
Application #
8125103
Study Section
Kidney, Nutrition, Obesity and Diabetes (KNOD)
Program Officer
Kusek, John W
Project Start
2007-09-01
Project End
2012-07-31
Budget Start
2011-08-01
Budget End
2012-07-31
Support Year
5
Fiscal Year
2011
Total Cost
$702,041
Indirect Cost
Name
Johns Hopkins University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
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Kim, Esther D; Sozio, Stephen M; Estrella, Michelle M et al. (2015) Cross-sectional association of volume, blood pressures, and aortic stiffness with left ventricular mass in incident hemodialysis patients: the Predictors of Arrhythmic and Cardiovascular Risk in End-Stage Renal Disease (PACE) study. BMC Nephrol 16:131
Parekh, Rulan S; Meoni, Lucy A; Jaar, Bernard G et al. (2015) Rationale and design for the Predictors of Arrhythmic and Cardiovascular Risk in End Stage Renal Disease (PACE) study. BMC Nephrol 16:63
McAdams-DeMarco, Mara A; Tan, Jingwen; Salter, Megan L et al. (2015) Frailty and Cognitive Function in Incident Hemodialysis Patients. Clin J Am Soc Nephrol 10:2181-9
Salter, Megan L; Gupta, Natasha; King, Elizabeth et al. (2014) Health-related and psychosocial concerns about transplantation among patients initiating dialysis. Clin J Am Soc Nephrol 9:1940-8
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Jaar, Bernard G; Zhang, Lili; Chembrovich, Svetlana V et al. (2014) Incidental findings on cardiac computed tomography in incident hemodialysis patients: the predictors of arrhythmic and cardiovascular events in end-stage renal disease (PACE) study. BMC Nephrol 15:68
Salter, Megan L; McAdams-Demarco, Mara A; Law, Andrew et al. (2014) Age and sex disparities in discussions about kidney transplantation in adults undergoing dialysis. J Am Geriatr Soc 62:843-9
Shafi, Tariq; Zager, Philip G; Sozio, Stephen M et al. (2014) Troponin I and NT-proBNP and the association of systolic blood pressure with outcomes in incident hemodialysis patients: the Choices for Healthy Outcomes in Caring for ESRD (CHOICE) Study. Am J Kidney Dis 64:443-51
Salter, Megan L; Orandi, Babak; McAdams-DeMarco, Mara A et al. (2014) Patient- and provider-reported information about transplantation and subsequent waitlisting. J Am Soc Nephrol 25:2871-7

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