Journal
PLOS ONE
Volume 10, Issue 5, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0126048
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Categories
Funding
- Agency for Healthcare Quality and Research AHRQ [R01-HS008365]
- National Heart, Lung, and Blood Institute (NHLBI) [RO1-HL-62985]
- National Institute of Diabetes & Digestive & Kidney Diseases NIDDK [R01-DK-059616, R01-DK-080123]
- National Kidney Foundation of Maryland Professional Development Award [K23-DK-083514]
- American Heart Association [01-4019-7N]
- National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health
- [R01-DK-072367]
- [K24-DK- 02643]
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Background and Objectives Numerous substances accumulate in the body in uremia but those contributing to cardiovascular morbidity and mortality in dialysis patients are still undefined. We examined the association of baseline free levels of four organic solutes that are secreted in the native kidney - p-cresol sulfate, indoxyl sulfate, hippurate and phenylacetylglutamine - with outcomes in hemodialysis patients. Design, Setting, Participants and Measurements We measured these solutes in stored specimens from 394 participants of a US national prospective cohort study of incident dialysis patients. We examined the relation of each solute and a combined solute index to cardiovascular mortality and morbidity (first cardiovascular event) using Cox proportional hazards regression adjusted for demographics, comorbidities, clinical factors and laboratory tests including Kt/V-UREA. Results Mean age of the patients was 57 years, 65% were white and 55% were male. In fully adjusted models, a higher p-cresol sulfate level was associated with a greater risk (HR per SD increase; 95% CI) of cardiovascular mortality (1.62; 1.17-2.25; p=0.004) and first cardiovascular event (1.60; 1.23-2.08; p<0.001). A higher phenylacetylglutamine level was associated with a greater risk of first cardiovascular event (1.37; 1.18-1.58; p<0.001). Patients in the highest quintile of the combined solute index had a 96% greater risk of cardiovascular mortality (1.96; 1.05-3.68; p=0.04) and 62% greater risk of first cardiovascular event (1.62; 1.12-2.35; p=0.01) compared with patients in the lowest quintile. Results were robust in sensitivity analyses. Conclusions Free levels of uremic solutes that are secreted by the native kidney are associated with a higher risk of cardiovascular morbidity and mortality in incident hemodialysis patients.
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