Chronic kidney disease (CKD) affects an estimated 19 million adults in the US and is associated with an elevated risk of cardiovascular disease (CVD) and mortality. This increased risk is partially explained by an elevated prevalence of several CVD risk factors, including hypertension, left ventricular hypertrophy (LVH) and heart failure, which increase in prevalence and severity as kidney function declines. African Americans are disproportionately afflicted with hypertension and CKD, and may be at higher risk of CVD associated with kidney dysfunction than are whites. Individuals with CKD are particularly susceptible to developing """"""""uremic cardiomyopathy,"""""""" a condition characterized by LVH, diastolic dysfunction and oxidative stress, which impart a significant increase in CVD risk. The mechanisms through which CKD causes these changes, however, are largely unknown. A new class of endogenous hormones, including ouabain and marinobufagenin, has recently been characterized. These hormones are significantly higher in persons with CKD, and may have effects on the cardiovascular system through several different pathways. We hypothesize that these hormones play a central role in the pathway leading from chronic kidney disease to LVH, heart failure and subsequent cardiovascular disease. We plan to study these associations in participants enrolled in the African American Study of Kidney Disease and Hypertension (AASK) Cohort Study. The AASK Cohort Study enrolled African Americans with hypertensive kidney disease. Participants underwent numerous clinic visits, tissue Doppler echocardiography, and 240hour ambulatory blood pressure monitoring. We propose to measure endogenous ouabain and marinobufagenin in a random sample of 255 AASK participants and coorelate these measures with markers of kidney function (estimated glomerular filtration rate, albuminuria), daytime and nighttime blood pressure, NT-proBNP, cardiac troponins I, and left ventricular geometry and function. Further research in this area has the potential to identify new targets for prognosis and treatment to reduce the elevated incidence of cardiovascular disease in this high-risk population.

Public Health Relevance

We hope to learn what role two cardiotonic hormones play in the development of cardiovascular disease among individuals with chronic kidney disease. This information may help identify targets for treatment or prevention to reduce the high risk of cardiovascular disease in patients with chronic kidney disease.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Exploratory/Developmental Grants (R21)
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Special Emphasis Panel (ZRG1-RUS-F (51))
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Eggers, Paul Wayne
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Johns Hopkins University
Public Health & Prev Medicine
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United States
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Chen, Teresa K; Estrella, Michelle M; Astor, Brad C et al. (2015) Longitudinal changes in hematocrit in hypertensive chronic kidney disease: results from the African-American Study of Kidney Disease and Hypertension (AASK). Nephrol Dial Transplant 30:1329-35
Scialla, Julia J; Astor, Brad C; Isakova, Tamara et al. (2013) Mineral metabolites and CKD progression in African Americans. J Am Soc Nephrol 24:125-35
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