Erythropoietin Dose and Mortality in Hemodialysis Patients: Marginal Structural Model to Examine Causality

It has been previously reported that a higher erythropoiesis stimulating agent (ESA) dose in hemodialysis patients is associated with adverse outcomes including mortality; however the causal relationship between ESA and mortality is still hotly debated. We hypothesize ESA dose indeed exhibits a dire...

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Main Authors: Elani Streja, Jongha Park, Ting-Yan Chan, Janet Lee, Melissa Soohoo, Connie M. Rhee, Onyebuchi A. Arah, Kamyar Kalantar-Zadeh
Format: Article
Language:English
Published: Wiley 2016-01-01
Series:International Journal of Nephrology
Online Access:http://dx.doi.org/10.1155/2016/6087134
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author Elani Streja
Jongha Park
Ting-Yan Chan
Janet Lee
Melissa Soohoo
Connie M. Rhee
Onyebuchi A. Arah
Kamyar Kalantar-Zadeh
author_facet Elani Streja
Jongha Park
Ting-Yan Chan
Janet Lee
Melissa Soohoo
Connie M. Rhee
Onyebuchi A. Arah
Kamyar Kalantar-Zadeh
author_sort Elani Streja
collection DOAJ
description It has been previously reported that a higher erythropoiesis stimulating agent (ESA) dose in hemodialysis patients is associated with adverse outcomes including mortality; however the causal relationship between ESA and mortality is still hotly debated. We hypothesize ESA dose indeed exhibits a direct linear relationship with mortality in models of association implementing the use of a marginal structural model (MSM), which controls for time-varying confounding and examines causality in the ESA dose-mortality relationship. We conducted a retrospective cohort study of 128 598 adult hemodialysis patients over a 5-year follow-up period to evaluate the association between weekly ESA (epoetin-α) dose and mortality risk. A MSM was used to account for baseline and time-varying covariates especially laboratory measures including hemoglobin level and markers of malnutrition-inflammation status. There was a dose-dependent positive association between weekly epoetin-α doses ≥18 000 U/week and mortality risk. Compared to ESA dose of <6 000 U/week, adjusted odds ratios (95% confidence interval) were 1.02 (0.94–1.10), 1.08 (1.00–1.18), 1.17 (1.06–1.28), 1.27 (1.15–1.41), and 1.52 (1.37–1.69) for ESA dose of 6 000 to <12 000, 12 000 to <18 000, 18 000 to <24 000, 24 000 to <30 000, and ≥30 000 U/week, respectively. High ESA dose may be causally associated with excessive mortality, which is supportive of guidelines which advocate for conservative management of ESA dosing regimen in hemodialysis patients.
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spelling doaj-art-cfbe9e1fe3ec4b5c90e2ce838ac89e552025-02-03T01:20:27ZengWileyInternational Journal of Nephrology2090-214X2090-21582016-01-01201610.1155/2016/60871346087134Erythropoietin Dose and Mortality in Hemodialysis Patients: Marginal Structural Model to Examine CausalityElani Streja0Jongha Park1Ting-Yan Chan2Janet Lee3Melissa Soohoo4Connie M. Rhee5Onyebuchi A. Arah6Kamyar Kalantar-Zadeh7Harold Simmons Center for Kidney Disease Research and Epidemiology, School of Medicine, University of California, Irvine, Orange, CA, USAHarold Simmons Center for Kidney Disease Research and Epidemiology, School of Medicine, University of California, Irvine, Orange, CA, USAHarold Simmons Center for Kidney Disease Research and Epidemiology, School of Medicine, University of California, Irvine, Orange, CA, USAHarold Simmons Center for Kidney Disease Research and Epidemiology, School of Medicine, University of California, Irvine, Orange, CA, USAHarold Simmons Center for Kidney Disease Research and Epidemiology, School of Medicine, University of California, Irvine, Orange, CA, USAHarold Simmons Center for Kidney Disease Research and Epidemiology, School of Medicine, University of California, Irvine, Orange, CA, USADepartment of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, CA, USAHarold Simmons Center for Kidney Disease Research and Epidemiology, School of Medicine, University of California, Irvine, Orange, CA, USAIt has been previously reported that a higher erythropoiesis stimulating agent (ESA) dose in hemodialysis patients is associated with adverse outcomes including mortality; however the causal relationship between ESA and mortality is still hotly debated. We hypothesize ESA dose indeed exhibits a direct linear relationship with mortality in models of association implementing the use of a marginal structural model (MSM), which controls for time-varying confounding and examines causality in the ESA dose-mortality relationship. We conducted a retrospective cohort study of 128 598 adult hemodialysis patients over a 5-year follow-up period to evaluate the association between weekly ESA (epoetin-α) dose and mortality risk. A MSM was used to account for baseline and time-varying covariates especially laboratory measures including hemoglobin level and markers of malnutrition-inflammation status. There was a dose-dependent positive association between weekly epoetin-α doses ≥18 000 U/week and mortality risk. Compared to ESA dose of <6 000 U/week, adjusted odds ratios (95% confidence interval) were 1.02 (0.94–1.10), 1.08 (1.00–1.18), 1.17 (1.06–1.28), 1.27 (1.15–1.41), and 1.52 (1.37–1.69) for ESA dose of 6 000 to <12 000, 12 000 to <18 000, 18 000 to <24 000, 24 000 to <30 000, and ≥30 000 U/week, respectively. High ESA dose may be causally associated with excessive mortality, which is supportive of guidelines which advocate for conservative management of ESA dosing regimen in hemodialysis patients.http://dx.doi.org/10.1155/2016/6087134
spellingShingle Elani Streja
Jongha Park
Ting-Yan Chan
Janet Lee
Melissa Soohoo
Connie M. Rhee
Onyebuchi A. Arah
Kamyar Kalantar-Zadeh
Erythropoietin Dose and Mortality in Hemodialysis Patients: Marginal Structural Model to Examine Causality
International Journal of Nephrology
title Erythropoietin Dose and Mortality in Hemodialysis Patients: Marginal Structural Model to Examine Causality
title_full Erythropoietin Dose and Mortality in Hemodialysis Patients: Marginal Structural Model to Examine Causality
title_fullStr Erythropoietin Dose and Mortality in Hemodialysis Patients: Marginal Structural Model to Examine Causality
title_full_unstemmed Erythropoietin Dose and Mortality in Hemodialysis Patients: Marginal Structural Model to Examine Causality
title_short Erythropoietin Dose and Mortality in Hemodialysis Patients: Marginal Structural Model to Examine Causality
title_sort erythropoietin dose and mortality in hemodialysis patients marginal structural model to examine causality
url http://dx.doi.org/10.1155/2016/6087134
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