Obesity and chronic kidney disease (CKD) are major public health problems. Obesity independent of its relationship with diabetes and hypertension is associated with the development and progression of kidney disease. However, higher body mass index (BMI) in those with pre-existing CKD is associated with lower mortality (obesity paradox). This may be due to the inability of BMI to differentiate fat mass and muscle mass, which may have opposite relationship with cardiovascular disease and death. Body fat distribution is a major factor of metabolic health with metabolic abnormalities correlating better with visceral than subcutaneous adipose tissue. Further, higher fitness levels among those with higher BMI are associated with a lower prevalence of cardiovascular risk factors and mortality that might explain this obesity paradox. Therefore, among Chronic Renal Insufficiency Cohort (CRIC) study participants, we propose (a) to examine whether visceral adiposity is associated with a higher incidence of composite outcomes (i.e., mortality, cardiovascular events, end stage renal disease, and 50% decline in estimated glomerular filtration rate), (b) to determine if physical fitness modifies the association between adiposity and outcomes, and (c) to study whether visceral adiposity and physical fitness are associated with altered adipokine profile, inflammation, insulin resistance, and oxidative stress. We propose to enroll 526 patients with varying degrees of kidney disease from 7 clinical centers involved in the CRIC study. Visceral adiposity will be measured by magnetic resonance imaging (MRI) of the abdomen using a standard protocol, and physical fitness will be measured using a 400 m walk test during routine CRIC study visits. The imaging data will be assessed at the central reading center at the Cleveland Clinic, and samples will be analyzed at the University of Pennsylvania central core laboratory. We have assembled a well-experienced, multi-disciplinary team to address these important public health questions. Results from this study will help us understand the independent and combined effects of visceral adiposity and physical fitness on cardiovascular disease and kidney disease progression among CKD patients. This study will also highlight potential pathways that mediate the relationship between adiposity and outcomes, which will become the focus of future therapeutic investigations in CKD.

Public Health Relevance

Chronic kidney disease and obesity are major public health problems. This study will help us understand the independent and combined effects of visceral adiposity and physical fitness on cardiovascular disease, renal disease progression and death among those with chronic kidney disease. Further, it will identify mechanisms that could be targeted to reduce the detrimental effects of visceral adiposity in those with kidney disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
1R01DK101500-01A1
Application #
8818718
Study Section
Special Emphasis Panel (ZDK1-GRB-G (O3))
Program Officer
Kusek, John W
Project Start
2014-09-22
Project End
2019-07-31
Budget Start
2014-09-22
Budget End
2015-07-31
Support Year
1
Fiscal Year
2014
Total Cost
$709,863
Indirect Cost
$195,949
Name
Cleveland Clinic Lerner
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
135781701
City
Cleveland
State
OH
Country
United States
Zip Code
44195