title: Administered paricalcitol dose and survival in hemodialysis patients: a marginal structural model analysis.
abstract: OBJECTIVE
  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.
authors.affiliation: Harold Simmons Center for Chronic Disease Research and Epidemiology, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.
authors.forename: Jessica E
authors.initials: JE
authors.lastname: Miller
authors.forename: Miklos Z
authors.initials: MZ
authors.lastname: Molnar
authors.forename: Csaba P
authors.initials: CP
authors.lastname: Kovesdy
authors.forename: Joshua J
authors.initials: JJ
authors.lastname: Zaritsky
authors.forename: Elani
authors.initials: E
authors.lastname: Streja
authors.forename: Isidro
authors.initials: I
authors.lastname: Salusky
authors.forename: Onyebuchi A
authors.initials: OA
authors.lastname: Arah
authors.forename: Kamyar
authors.initials: K
authors.lastname: Kalantar-Zadeh
mesh_terms: D000368:Aged; D050071:Bone Density Conservation Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004872:Ergocalciferols / Q000008:administration & dosage* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000097:blood / Q000150:complications / Q000188:drug therapy; D007676:Kidney Failure, Chronic / Q000097:blood / Q000209:etiology / Q000401:mortality / Q000628:therapy; D008297:Male; D008875:Middle Aged; D008961:Models, Structural; D009026:Mortality / Q000639:trends; D010281:Parathyroid Hormone / Q000097:blood; D011237:Predictive Value of Tests; D057216:Propensity Score; D016016:Proportional Hazards Models; D018167:Receptors, Calcitriol / Q000819:agonists; D006435:Renal Dialysis / Q000401:mortality*; D016019:Survival Analysis
chemical_list: D050071:Bone Density Conservation Agents; D004872:Ergocalciferols; D010281:Parathyroid Hormone; D018167:Receptors, Calcitriol; C084656:paricalcitol