Free levels of selected organic solutes and cardiovascular morbidity and mortality in hemodialysis patients

Results from the retained organic solutes and clinical outcomes (ROSCO) investigators

Tariq Shafi, Timothy W. Meyer, Thomas H. Hostetter, Michal L. Melamed, Rulan S. Parekh, Seungyoung Hwang, Tanushree Banerjee, Josef Coresh, Neil R. Powe

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

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/<inf>VUREA</inf>. 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; pA higher phenylacetylglutamine level was associated with a greater risk of first cardiovascular event (1.37; 1.18?1.58; p[ampi]lt;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.

Original languageEnglish (US)
Article numbere0126048
JournalPLoS One
Volume10
Issue number5
DOIs
StatePublished - May 4 2015

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hemodialysis
solutes
morbidity
Renal Dialysis
Research Personnel
Morbidity
Mortality
Dialysis
p-cresol
sulfates
Indican
dialysis
kidneys
Free Association
Kidney
uremia
Hazards
Uremia
cohort studies
Comorbidity

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Free levels of selected organic solutes and cardiovascular morbidity and mortality in hemodialysis patients : Results from the retained organic solutes and clinical outcomes (ROSCO) investigators. / Shafi, Tariq; Meyer, Timothy W.; Hostetter, Thomas H.; Melamed, Michal L.; Parekh, Rulan S.; Hwang, Seungyoung; Banerjee, Tanushree; Coresh, Josef; Powe, Neil R.

In: PLoS One, Vol. 10, No. 5, e0126048, 04.05.2015.

Research output: Contribution to journalArticle

Shafi, Tariq ; Meyer, Timothy W. ; Hostetter, Thomas H. ; Melamed, Michal L. ; Parekh, Rulan S. ; Hwang, Seungyoung ; Banerjee, Tanushree ; Coresh, Josef ; Powe, Neil R. / Free levels of selected organic solutes and cardiovascular morbidity and mortality in hemodialysis patients : Results from the retained organic solutes and clinical outcomes (ROSCO) investigators. In: PLoS One. 2015 ; Vol. 10, No. 5.
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abstract = "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/VUREA. 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; pA higher phenylacetylglutamine level was associated with a greater risk of first cardiovascular event (1.37; 1.18?1.58; p[ampi]lt;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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T2 - Results from the retained organic solutes and clinical outcomes (ROSCO) investigators

AU - Shafi, Tariq

AU - Meyer, Timothy W.

AU - Hostetter, Thomas H.

AU - Melamed, Michal L.

AU - Parekh, Rulan S.

AU - Hwang, Seungyoung

AU - Banerjee, Tanushree

AU - Coresh, Josef

AU - Powe, Neil R.

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Y1 - 2015/5/4

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