This is an initial submission for a K23 award by Dr. Meyeon Park at the University of California, San Francisco. Dr. Park is establishing herself as a young investigator in patient-oriented clinical research of chronic kidney disease (CKD). This K23 award will provide Dr. Park with the support necessary to accomplish the following goals: 1) to study the mechanisms of kidney injury and CKD onset in individuals with cardiovascular disease; 2) to study novel risk factor pathways in individuals with cardiovascular disease who develop CKD; and 3) to become an expert in the novel application of a method of magnetic resonance imaging for detecting kidney hypoxia in vivo. To achieve these goals, Dr. Park has assembled a mentoring team led by a primary mentor, Dr. Michael Shlipak, Professor and Chief of the Division of General Internal Medicine at the San Francisco VA Medical Center, and a co-mentor, Dr. Chi-yuan Hsu, Professor and Chief of the Division of Nephrology at UCSF. Her larger mentoring team also includes Dr. Eric Vittinghoff, Professor in the Division of Biostatistic at UCSF and an expert in longitudinal analyses of repeated measures. Dr. Peter Ganz, Dr. Yerem Yeghiazarians, and Dr. Zhen Jane Wang are close collaborators and scientific advisors who will lend scientific expertise in the areas of cardiovascular biomarkers, coronary angiography, and renal imaging, respectively. Cardiovascular disease (CVD) is extremely prevalent in the U.S. adult population and is a strong and independent risk factor for development of CKD, which adds excess morbidity and mortality to an already deadly condition. Few studies have focused on identifying risk factors for development of CKD in this group, and there is incomplete understanding of the mechanisms of early kidney disease onset in this setting. Dr. Park's research will first examine the impact of CVD on kidney injury detected by novel urine biomarkers and on clinically evident kidney disease outcomes (Aim 1). She will then focus on individuals with ischemic heart disease to examine candidate risk factor pathways leading from atherosclerosis to reduced kidney function in this group, including potentially via acute kidney injury (Aim 2). Finally, she will study kidney hypoxia using Blood Oxygen Level-Dependent magnetic resonance imaging (BOLD-MRI) and correlate this with kidney injury markers (Aim 3). This research will form the basis for future work investigating strategies for CKD risk stratification and early detection and intervention among CVD patients, which will be proposed in an R01 grant application before the end of the K award period.

Public Health Relevance

Cardiovascular disease is a worldwide health problem and a major risk factor for kidney disease and death. The development of chronic kidney disease in a person with cardiovascular disease complicates management, reduces health status, and increases mortality risk substantially. As the mechanisms for the development of kidney disease in these individuals are not understood, we plan to investigate how cardiovascular disease leads to kidney disease.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Mentored Patient-Oriented Research Career Development Award (K23)
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Kidney, Urologic and Hematologic Diseases D Subcommittee (DDK)
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Rankin, Tracy L
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University of California San Francisco
Internal Medicine/Medicine
Schools of Medicine
San Francisco
United States
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Park, Meyeon; Maristany, Daniela; Huang, Debbie et al. (2017) Associations of tumor necrosis factor alpha receptor type 1 with kidney function decline, cardiovascular events, and mortality risk in persons with coronary artery disease: Data from the Heart and Soul Study. Atherosclerosis 263:68-73
Park, M; Katz, R; Shlipak, M G et al. (2017) Urinary Markers of Fibrosis and Risk of Cardiovascular Events and Death in Kidney Transplant Recipients: The FAVORIT Trial. Am J Transplant 17:2640-2649
Park, Meyeon; Hsu, Chi-Yuan; Go, Alan S et al. (2017) Urine Kidney Injury Biomarkers and Risks of Cardiovascular Disease Events and All-Cause Death: The CRIC Study. Clin J Am Soc Nephrol 12:761-771
Park, Meyeon; Shlipak, Michael G; Thiessen-Philbrook, Heather et al. (2016) Association of Peak Changes in Plasma Cystatin C and Creatinine With Death After Cardiac Operations. Ann Thorac Surg 101:1395-401
Park, Meyeon; Kulkarni, Ameya; Beatty, Alexis et al. (2015) Soluble endothelial cell selective adhesion molecule and cardiovascular outcomes in patients with stable coronary disease: A report from the Heart and Soul Study. Atherosclerosis 243:546-52
Park, Meyeon (2015) Islands in the stream: the risk of kidney disease from cardiovascular disease. Am J Kidney Dis 65:647-9
Park, Meyeon; Shlipak, Michael G; Vittinghoff, Eric et al. (2015) Associations of kidney injury markers with subclinical cardiovascular disease: the Multi-Ethnic Study of Atherosclerosis. Clin Nephrol 84:358-63
Park, Meyeon; Vittinghoff, Eric; Shlipak, Michael G et al. (2014) Associations of N-terminal pro-B-type natriuretic peptide with kidney function decline in persons without clinical heart failure in the Heart and Soul Study. Am Heart J 168:931-9.e2
Park, Meyeon; Vittinghoff, Eric; Ganz, Peter et al. (2014) Role of soluble endothelial cell-selective adhesion molecule biomarker in albuminuria and kidney function changes in patients with coronary artery disease: the Heart and Soul Study. Arterioscler Thromb Vasc Biol 34:231-6