Mortality rates for hemodialysis (HD) patients in the United States are six to nine-fold higher than in the general population. Concerns about the role of inflammation as a mediator of adverse outcomes among HD patients has led to increasing clinical use of inflammatory biomarkers such as C-reactive protein (CRP), in many countries outside of North America, without substantial evidence that this practice improves outcomes. The overall project goal is to determine whether CRP measurement may improve clinical outcomes in maintenance HD patients. The Dialysis Outcomes and Practice Patterns Study (DOPPS), a prospective cohort study, offers a unique opportunity to study changes in CRP over time, how patient characteristics and treatments affect CRP, and how longitudinal CRP measures predict outcomes. This specific study hypothesis proposes that (1) the risk of adverse outcomes is highest in hemodialysis patients with CRP levels that remain high over time, intermediate in patients with transient rises in CRP, and lowest in patients with CRP levels that remain low over time, and (2) the following treatments lower CRP levels: medications including vitamin D analogues, angiotensin-converting enzyme (ACE ) inhibitors, angiotensin receptor blockers (ARBs), and aspirin;and dialysis treatments including longer treatment time and hemodiafiltration.
Specific Aim #1 will describe patterns of change in CRP level over time.
Specific Aim #2 will characterize the associations of baseline patient characteristics with longitudinal CRP levels.
Specific Aim #3 will characterize the associations of selected medications and dialysis treatment variables with longitudinal CRP levels, with the goal to identify therapies associated with lower CRP levels that may merit further study in randomized trials.
Specific Aim #4 will examine longitudinal CRP as a predictor of outcomes, including mortality, cause-specific mortality, and hospitalizations.

Public Health Relevance

The death rate for hemodialysis patients is unacceptably high, and a major contributor is thought to be inflammation, represented by blood levels of C-reactive protein (CRP). In many countries, but not in the United States, dialysis physicians measure CRP levels often. This study will determine patient characteristics and dialysis treatment practices associated with changes in CRP levels over time, and the associations of changing CRP levels with patient survival, to help clarify whether measuring CRP may help to reduce the number of deaths in this high-risk population.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Postdoctoral Individual National Research Service Award (F32)
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Special Emphasis Panel (ZDK1-GRB-G (M1))
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Rankin, Tracy L
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University of Michigan Ann Arbor
Internal Medicine/Medicine
Schools of Medicine
Ann Arbor
United States
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