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.
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.
|Navaneethan, Sankar D; Schold, Jesse D; Jolly, Stacey E et al. (2017) Diabetes Control and the Risks of ESRD and Mortality in Patients With CKD. Am J Kidney Dis 70:191-198|
|Navaneethan, Sankar D; Schold, Jesse D; Jolly, Stacey E et al. (2017) Blood pressure parameters are associated with all-cause and cause-specific mortality in chronic kidney disease. Kidney Int 92:1272-1281|
|Agrawal, Varun; Navaneethan, Sankar D (2016) Bariatric surgery for obesity-associated decline in kidney function: filling the knowledge gap? Kidney Int 90:28-30|
|Yan, Jingyin; Navaneethan, Sankar D (2016) Copeptin and Decline in Kidney Function. Am J Nephrol 44:19-21|
|Navaneethan, Sankar D; Roy, Jason; Tao, Kelvin et al. (2016) Prevalence, Predictors, and Outcomes of Pulmonary Hypertension in CKD. J Am Soc Nephrol 27:877-86|
|Navaneethan, Sankar D; Schold, Jesse D; Arrigain, Susana et al. (2016) Body mass index and causes of death in chronic kidney disease. Kidney Int 89:675-82|
|Navaneethan, Sankar D; Schold, Jesse D; Huang, Haiquan et al. (2016) Mortality Outcomes of Patients with Chronic Kidney Disease and Chronic Obstructive Pulmonary Disease. Am J Nephrol 43:39-46|
|Navaneethan, Sankar D; Mandayam, Sreedhar; Arrigain, Susana et al. (2016) Obstructive and Restrictive Lung Function Measures and CKD: National Health and Nutrition Examination Survey (NHANES) 2007-2012. Am J Kidney Dis 68:414-21|
|Nakhoul, Georges N; Schold, Jesse D; Arrigain, Susana et al. (2015) Implantable cardioverter-defibrillators in patients with CKD: a propensity-matched mortality analysis. Clin J Am Soc Nephrol 10:1119-27|
|Navaneethan, Sankar D; Dweik, Raed A (2015) Elevated pulmonary pressure: A novel risk marker in kidney disease? Kidney Int 88:7-9|
Showing the most recent 10 out of 14 publications