Chronic kidney disease (CKD) is a common condition that manifests as decreased kidney function and/or markers of kidney damage. As CKD progresses toward end-stage renal disease (ESRD), patients have an increased risk of serious complications. ESRD presents a burden both to patients and the health care system. Therefore, one of the main goals of nephrologists caring for patients with CKD to slow CKD progression by intervening on risk factors that are associated with progression. The role of hyperuricemia in CKD progression is controversial, with conflicting results from observational studies. As advanced CKD is characterized by structural and functional changes within the kidney, risk factors for progression may not be constant across all stages. It is unknown whether hyperuricemia is a risk factor for CKD progression in individuals with less advanced CKD, as these patients were not enrolled in prior observational studies. In addition, there is a paucity of data regarding the association between uric acid (UA) and risk of CKD progression in individuals with CKD due to glomerular disease. We propose a retrospective cohort study that examines the relationship between UA and subsequent CKD progression using a population- based cohort from the United Kingdom-The Health Improvement Network (THIN) database. Patients with CKD will be identified, and those who have had a UA level recorded will be eligible for enrollment. The UA level is the exposure, and the primary outcome is the slope of change in kidney function over time. These longitudinal data will be analyzed by fitting mixed effects models.
Aim 1 : To assess if the association between UA level and CKD progression differs by baseline CKD severity.
Aim 2 : To assess if the association between UA level and CKD progression differs by CKD etiology.
Aim 3 : To acquire advanced training in epidemiology, biostatistics, and analytical techniques central to the conduct of epidemiological research through coursework and mentored research, propelling forward the applicant's development into a fully independent investigator. The identification of subgroups of patients with CKD who have an increased risk of CKD progression due to a potentially modifiable risk factor, such as hyperuricemia, has major implications in the care of these patients. The results of the proposed study will enhance our current understanding of CKD progression and represents an opportunity for discovery that may lead to the reduction of the burden of morbidity associated with CKD. The proposed study will allow the applicant to build upon skills learned in the Masters of Science in Clinical Epidemiology program. Classroom didactics in study design and analytical techniques will provide necessary tools for developing a K23 application as the applicant embarks on a career as an independent investigator.

Public Health Relevance

Over twenty-six million American adults have chronic kidney disease;and these patients are at risk for progression to end-stage renal disease, which is associated with considerable morbidity, mortality, and health care costs. By targeting risk factors for chronic kidney disease progression, nephrologists hope to slow this process. The proposed project seeks to identify subgroups of individuals with chronic kidney disease who are especially sensitive to the effects of uric acid, a potentially modifiable risk factor for progression;and th results of this project will advance our understanding of chronic kidney disease progression and has the potential to transform the nephrologist's approach to slowing progression.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Postdoctoral Individual National Research Service Award (F32)
Project #
Application #
Study Section
Special Emphasis Panel (ZDK1-GRB-G (M1))
Program Officer
Rankin, Tracy L
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Pennsylvania
Internal Medicine/Medicine
Schools of Medicine
United States
Zip Code
Denker, Matthew G; Cohen, Debbie L (2014) Use of continuous positive airway pressure for sleep apnea in the treatment of hypertension. Curr Opin Nephrol Hypertens 23:462-7
Denker, Matthew G; Cohen, Debbie L (2013) What is an appropriate blood pressure goal for the elderly: review of recent studies and practical recommendations. Clin Interv Aging 8:1505-17