Administered paricalcitol dose and survival in hemodialysis patients: A marginal structural model analysis

Authors

  • Jessica E Miller,

    1. Harold Simmons Center for Chronic Disease Research and Epidemiology, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA
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  • Miklos Z Molnar,

    1. Harold Simmons Center for Chronic Disease Research and Epidemiology, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA
    2. Institute of Pathophysiology, Semmelweis University, Budapest, Hungary
    3. Department of Medicine, Division of Nephrology, University Health Network, University of Toronto, Toronto, Ontario, Canada
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  • Csaba P Kovesdy,

    1. Division of Nephrology, Memphis Veterans Affairs Medical Center, Memphis, TN, USA
    2. Division of Nephrology, University of Tennessee Health Science Center, Memphis, TN, USA
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  • Joshua J Zaritsky,

    1. David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
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  • Elani Streja,

    1. Harold Simmons Center for Chronic Disease Research and Epidemiology, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA
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  • Isidro Salusky,

    1. David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
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  • Onyebuchi A Arah,

    1. Department of Epidemiology, UCLA School of Public Health, Los Angeles, CA, USA
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  • Kamyar Kalantar-Zadeh

    Corresponding author
    1. Division of Nephrology and Hypertension, University of California Irvine Medical Center, Orange, CA, USA
    • Harold Simmons Center for Chronic Disease Research and Epidemiology, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA
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Kamyar Kalantar-Zadeh, MD, MPH, PHD, Harold Simmons Program for Kidney Disease Research and Epidemiology, Division of Nephrology and Hypertension, University of California Irvine, School of Medicine, 101 The City Drive South, City Tower, Suite 400 - ZOT: 4088, Orange, California 92868-3217, USA. E-mail: kkz@uci.edu

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 <10 µg/week) versus high (≥10 µg/week) dose of administered paricalcitol over time in a contemporary cohort of 15 442 MHD patients (age 64 ± 15 years, 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. Copyright © 2012 John Wiley & Sons, Ltd.

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