Administered paricalcitol dose and survival in hemodialysis patients

A marginal structural model analysis

Jessica E. Miller, Miklos Z. Molnar, Csaba Kovesdy, Joshua J. Zaritsky, Elani Streja, Isidro Salusky, Onyebuchi A. Arah, Kamyar Kalantar-Zadeh

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Purpose: Several observational studies have indicated that vitamin D receptor activators (VDRA), including paricalcitol, are associated with greater survival in maintenance hemodialysis (MHD) patients. However, patients with higher serum parathyroid hormone, a surrogate of higher death risk, are usually given higher VDRA doses, which can lead to confounding by indication and attenuate the expected survival advantage of high VDRA doses. Methods: We examined mortality-predictability of low (>1 but <10μg/week) versus high (≥10μg/week) dose of administered paricalcitol over time in a contemporary cohort of 15442 MHD patients (age 64±15years, 55% men, 44% diabetes, 35% African-Americans) from all DaVita dialysis clinics across the USA (7/2001-6/2006 with survival follow-ups until 6/2007) using conventional Cox regression, propensity score (PS) matching, and marginal structural model (MSM) analyses. Results: In our conventional Cox models and PS matching models, low dose of paricalcitol was not associated with mortality either in baseline (hazard ratio (HR): 1.03, 95% confidence interval (CI): (0.97-1.09)) and (HR: 0.99, 95%CI:(0.86-1.14)) or time-dependent (HR: 1.04, 95%CI: (0.98-1.10)) and (HR: 1.12, 95%CI: (0.98-1.28)) models, respectively. In contrast, compared to high dose of paricalcitol, low dose was associated with a 26% higher risk of mortality (HR: 1.26, 95%CI: (1.19-1.35)) in MSM. The association between dose of paricalcitol and mortality was robust in almost all subgroups of patients using MSMs. Conclusions: Higher dose of paricalcitol appears causally associated with greater survival in MHD patients. Randomized controlled trials need to verify the survival effect of paricalcitol dose in MHD patients are indicated.

Original languageEnglish (US)
Pages (from-to)1232-1239
Number of pages8
JournalPharmacoepidemiology and Drug Safety
Volume21
Issue number11
DOIs
StatePublished - Nov 1 2012

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Structural Models
Renal Dialysis
Survival
Calcitriol Receptors
Confidence Intervals
Propensity Score
Mortality
paricalcitol
Parathyroid Hormone
Proportional Hazards Models
African Americans
Observational Studies
Dialysis
Randomized Controlled Trials
Maintenance
Serum

All Science Journal Classification (ASJC) codes

  • Epidemiology
  • Pharmacology (medical)

Cite this

Miller, J. E., Molnar, M. Z., Kovesdy, C., Zaritsky, J. J., Streja, E., Salusky, I., ... Kalantar-Zadeh, K. (2012). Administered paricalcitol dose and survival in hemodialysis patients: A marginal structural model analysis. Pharmacoepidemiology and Drug Safety, 21(11), 1232-1239. https://doi.org/10.1002/pds.3349

Administered paricalcitol dose and survival in hemodialysis patients : A marginal structural model analysis. / Miller, Jessica E.; Molnar, Miklos Z.; Kovesdy, Csaba; Zaritsky, Joshua J.; Streja, Elani; Salusky, Isidro; Arah, Onyebuchi A.; Kalantar-Zadeh, Kamyar.

In: Pharmacoepidemiology and Drug Safety, Vol. 21, No. 11, 01.11.2012, p. 1232-1239.

Research output: Contribution to journalArticle

Miller, JE, Molnar, MZ, Kovesdy, C, Zaritsky, JJ, Streja, E, Salusky, I, Arah, OA & Kalantar-Zadeh, K 2012, 'Administered paricalcitol dose and survival in hemodialysis patients: A marginal structural model analysis', Pharmacoepidemiology and Drug Safety, vol. 21, no. 11, pp. 1232-1239. https://doi.org/10.1002/pds.3349
Miller, Jessica E. ; Molnar, Miklos Z. ; Kovesdy, Csaba ; Zaritsky, Joshua J. ; Streja, Elani ; Salusky, Isidro ; Arah, Onyebuchi A. ; Kalantar-Zadeh, Kamyar. / Administered paricalcitol dose and survival in hemodialysis patients : A marginal structural model analysis. In: Pharmacoepidemiology and Drug Safety. 2012 ; Vol. 21, No. 11. pp. 1232-1239.
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abstract = "Purpose: Several observational studies have indicated that vitamin D receptor activators (VDRA), including paricalcitol, are associated with greater survival in maintenance hemodialysis (MHD) patients. However, patients with higher serum parathyroid hormone, a surrogate of higher death risk, are usually given higher VDRA doses, which can lead to confounding by indication and attenuate the expected survival advantage of high VDRA doses. Methods: We examined mortality-predictability of low (>1 but <10μg/week) versus high (≥10μg/week) dose of administered paricalcitol over time in a contemporary cohort of 15442 MHD patients (age 64±15years, 55{\%} men, 44{\%} diabetes, 35{\%} African-Americans) from all DaVita dialysis clinics across the USA (7/2001-6/2006 with survival follow-ups until 6/2007) using conventional Cox regression, propensity score (PS) matching, and marginal structural model (MSM) analyses. Results: In our conventional Cox models and PS matching models, low dose of paricalcitol was not associated with mortality either in baseline (hazard ratio (HR): 1.03, 95{\%} confidence interval (CI): (0.97-1.09)) and (HR: 0.99, 95{\%}CI:(0.86-1.14)) or time-dependent (HR: 1.04, 95{\%}CI: (0.98-1.10)) and (HR: 1.12, 95{\%}CI: (0.98-1.28)) models, respectively. In contrast, compared to high dose of paricalcitol, low dose was associated with a 26{\%} higher risk of mortality (HR: 1.26, 95{\%}CI: (1.19-1.35)) in MSM. The association between dose of paricalcitol and mortality was robust in almost all subgroups of patients using MSMs. Conclusions: Higher dose of paricalcitol appears causally associated with greater survival in MHD patients. Randomized controlled trials need to verify the survival effect of paricalcitol dose in MHD patients are indicated.",
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T1 - Administered paricalcitol dose and survival in hemodialysis patients

T2 - A marginal structural model analysis

AU - Miller, Jessica E.

AU - Molnar, Miklos Z.

AU - Kovesdy, Csaba

AU - Zaritsky, Joshua J.

AU - Streja, Elani

AU - Salusky, Isidro

AU - Arah, Onyebuchi A.

AU - Kalantar-Zadeh, Kamyar

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N2 - Purpose: Several observational studies have indicated that vitamin D receptor activators (VDRA), including paricalcitol, are associated with greater survival in maintenance hemodialysis (MHD) patients. However, patients with higher serum parathyroid hormone, a surrogate of higher death risk, are usually given higher VDRA doses, which can lead to confounding by indication and attenuate the expected survival advantage of high VDRA doses. Methods: We examined mortality-predictability of low (>1 but <10μg/week) versus high (≥10μg/week) dose of administered paricalcitol over time in a contemporary cohort of 15442 MHD patients (age 64±15years, 55% men, 44% diabetes, 35% African-Americans) from all DaVita dialysis clinics across the USA (7/2001-6/2006 with survival follow-ups until 6/2007) using conventional Cox regression, propensity score (PS) matching, and marginal structural model (MSM) analyses. Results: In our conventional Cox models and PS matching models, low dose of paricalcitol was not associated with mortality either in baseline (hazard ratio (HR): 1.03, 95% confidence interval (CI): (0.97-1.09)) and (HR: 0.99, 95%CI:(0.86-1.14)) or time-dependent (HR: 1.04, 95%CI: (0.98-1.10)) and (HR: 1.12, 95%CI: (0.98-1.28)) models, respectively. In contrast, compared to high dose of paricalcitol, low dose was associated with a 26% higher risk of mortality (HR: 1.26, 95%CI: (1.19-1.35)) in MSM. The association between dose of paricalcitol and mortality was robust in almost all subgroups of patients using MSMs. Conclusions: Higher dose of paricalcitol appears causally associated with greater survival in MHD patients. Randomized controlled trials need to verify the survival effect of paricalcitol dose in MHD patients are indicated.

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