Among individuals with chronic kidney disease (CKD) receiving maintenance dialysis therapy the proportion of African American patients is significantly higher compared to their non-Hispanic white counterparts, and traditional risk factors of cardiovascular disease such as hypercholesterolemia, hypertension and obesity show seemingly anomalous, inverse associations with adverse outcomes. The exceptionally high prevalence of end- stage renal disease (ESRD) among African Americans is likely a result of the complex interaction of their higher rates of CKD incidence and/or faster CKD progression, lower mortality, and lower likelihood of kidney transplantation. The anomalous cardiovascular risk factor profile in ESRD could be the result of short-term competing risks related to malnutrition and inflammation, with the seemingly unfavorable traditional cardiovascular risk factors associating with a better nutritional state, which could differentially affect African Americans an hence provide one explanation for their better survival in ESRD. Whether similar paradoxical differences in mortality rates in non-dialysis dependent CKD stages exist is not clear; their presence, extent, the CKD stage of its occurrence and their mechanisms of action all need to be clarified in sufficient detail to allow for the design of proper diagnostic and interventional strategies towards cardiovascular risk reduction and towards alleviating racial disparities in outcomes. In the spirit of PA-09-196 we will utilize data obtained from the national VA research database which is the only large administrative database with detailed socio-demographic and clinical information on very large numbers of individuals (over 4 million individuals including ove 0.5 million with CKD) across all parts of the US. We will examine the population-wide dynamic effects of incident CKD and mortality on racial composition and on changes in cardiovascular risk factor profiles by examining longitudinally a cohort of patients with normal estimated glomerular filtration rate. We will explore the effects of various socio-demographic characteristics, co-morbidities, biochemical measurements and medication use on mortality and progressive CKD using complex epidemiologic methods including joint modeling to assess the effect of longitudinal changes in risk factor parameters on mortality and marginal structural models in order to adjust for both baseline and time-dependent confounders. This three-year project will generate a wealth of information to more reliably examine the above hypotheses related to racial and cardiovascular discrepancies in the outcomes of patients with all levels of kidney function that could have significant public health implications.

Public Health Relevance

CKD is a prototype for a chronic disease state and is recognized as a global epidemic and a Healthy People 2020 priority area. It is also now recognized as a CVD risk factor and most studies suggest the presence of CKD is a more powerful predictor of CV events than all traditional CV risk factors with the possible exceptions of diabetes and hypertension. Advancing our understanding of the changes in mortality risk profile from normal eGFR to advancing stages of CKD will yield invaluable insights into socio-cultural, clinical and biologic influences on mortality risk and how they interact during the development of a chronic disease state. Given the role of chronic diseases on both the personal and financial burden to our nation, this study is designed to enhance our understanding of chronic disease prevention and early intervention, and ultimately improve patient outcomes and reduce healthcare costs.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK096920-03
Application #
8811934
Study Section
Special Emphasis Panel (ZRG1-PSE-H (02))
Program Officer
Kusek, John W
Project Start
2013-03-15
Project End
2016-02-29
Budget Start
2015-03-01
Budget End
2016-02-29
Support Year
3
Fiscal Year
2015
Total Cost
$300,017
Indirect Cost
$33,307
Name
University of Tennessee Health Science Center
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
941884009
City
Memphis
State
TN
Country
United States
Zip Code
38103
Rhee, Connie M; Kalantar-Zadeh, Kamyar; Ravel, Vanessa et al. (2018) Thyroid Status and Death Risk in US Veterans With Chronic Kidney Disease. Mayo Clin Proc 93:573-585
Grams, Morgan E; Sang, Yingying; Ballew, Shoshana H et al. (2018) Predicting timing of clinical outcomes in patients with chronic kidney disease and severely decreased glomerular filtration rate. Kidney Int 93:1442-1451
Ferrey, Antoney; You, Amy S; Kovesdy, Csaba P et al. (2018) Dialysate Potassium and Mortality in a Prospective Hemodialysis Cohort. Am J Nephrol 47:415-423
Chou, Jason A; Streja, Elani; Nguyen, Danh V et al. (2018) Intradialytic hypotension, blood pressure changes and mortality risk in incident hemodialysis patients. Nephrol Dial Transplant 33:149-159
Sumida, Keiichi; Molnar, Miklos Z; Potukuchi, Praveen K et al. (2018) Treatment of rheumatoid arthritis with biologic agents lowers the risk of incident chronic kidney disease. Kidney Int 93:1207-1216
Streja, Elani; Kalantar-Zadeh, Kamyar; Molnar, Miklos Z et al. (2018) Radical versus partial nephrectomy, chronic kidney disease progression and mortality in US veterans. Nephrol Dial Transplant 33:95-101
Rhee, Connie M; Obi, Yoshitsugu; Mathew, Anna T et al. (2018) Precision Medicine in the Transition to Dialysis and Personalized Renal Replacement Therapy. Semin Nephrol 38:325-335
Obi, Yoshitsugu; Streja, Elani; Mehrotra, Rajnish et al. (2018) Impact of Obesity on Modality Longevity, Residual Kidney Function, Peritonitis, and Survival Among Incident Peritoneal Dialysis Patients. Am J Kidney Dis 71:802-813
Soohoo, Melissa; Streja, Elani; Obi, Yoshitsugu et al. (2018) Predialysis Kidney Function and Its Rate of Decline Predict Mortality and Hospitalizations After Starting Dialysis. Mayo Clin Proc 93:1074-1085
Rhee, Connie M; Kovesdy, Csaba P; Kalantar-Zadeh, Kamyar (2017) Risks of Metformin in Type 2 Diabetes and Chronic Kidney Disease: Lessons Learned from Taiwanese Data. Nephron 135:147-153

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