title: Recent changes in therapeutic approaches and association with outcomes among patients with secondary hyperparathyroidism on chronic hemodialysis: the DOPPS study.
abstract: OBJECTIVE
  Elevated parathyroid hormone levels may be associated with adverse clinical outcomes in patients on dialysis. After the introduction of practice guidelines suggesting higher parathyroid hormone targets than those previously recommended, changes in parathyroid hormone levels and treatment regimens over time have not been well documented.
  
  
  METHODS
  Using data from the international Dialysis Outcomes and Practice Patterns Study, trends in parathyroid hormone levels and secondary hyperparathyroidism therapies over the past 15 years and the associations between parathyroid hormone and clinical outcomes are reported; 35,655 participants from the Dialysis Outcomes and Practice Patterns Study phases 1-4 (1996-2011) were included.
  
  
  RESULTS
  Median parathyroid hormone increased from phase 1 to phase 4 in all regions except for Japan, where it remained stable. Prescriptions of intravenous vitamin D analogs and cinacalcet increased and parathyroidectomy rates decreased in all regions over time. Compared with 150-300 pg/ml, in adjusted models, all-cause mortality risk was higher for parathyroid hormone=301-450 (hazard ratio, 1.09; 95% confidence interval, 1.01 to 1.18) and >600 pg/ml (hazard ratio, 1.23; 95% confidence interval, 1.12 to 1.34). Parathyroid hormone >600 pg/ml was also associated with higher risk of cardiovascular mortality as well as all-cause and cardiovascular hospitalizations. In a subgroup analysis of 5387 patients not receiving vitamin D analogs or cinacalcet and with no prior parathyroidectomy, very low parathyroid hormone (<50 pg/ml) was associated with mortality (hazard ratio, 1.25; 95% confidence interval, 1.04 to 1.51).
  
  
  CONCLUSIONS
  In a large international sample of patients on hemodialysis, parathyroid hormone levels increased in most countries, and secondary hyperparathyroidism treatments changed over time. Very low and very high parathyroid hormone levels were associated with adverse outcomes. In the absence of definitive evidence in support of a specific parathyroid hormone target, there is an urgent need for additional research to inform clinical practice.
authors.affiliation: Arbor Research Collaborative for Health, Ann Arbor, Michigan; Vanderbilt University Medical Center, Nashville, Tennessee francesca.tentori@ArborResearch.org.
authors.forename: Francesca
authors.initials: F
authors.lastname: Tentori
authors.affiliation: Arbor Research Collaborative for Health, Ann Arbor, Michigan;
authors.forename: Mia
authors.initials: M
authors.lastname: Wang
authors.affiliation: Arbor Research Collaborative for Health, Ann Arbor, Michigan;
authors.forename: Brian A
authors.initials: BA
authors.lastname: Bieber
authors.affiliation: Arbor Research Collaborative for Health, Ann Arbor, Michigan;
authors.forename: Angelo
authors.initials: A
authors.lastname: Karaboyas
authors.affiliation: Arbor Research Collaborative for Health, Ann Arbor, Michigan; Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, Michigan;
authors.forename: Yun
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden;
authors.forename: Stefan H
authors.initials: SH
authors.lastname: Jacobson
authors.affiliation: University of Naples Federico II, Naples, Italy;
authors.forename: Vittorio E
authors.initials: VE
authors.lastname: Andreucci
authors.affiliation: Division of Nephrology, Endocrinology, and Metabolism, Tokai University School of Medicine, Isehara, Japan;
authors.forename: Masafumi
authors.initials: M
authors.lastname: Fukagawa
authors.affiliation: Clinical Epidemiology, Inserm CIC-EC and Nephrology Department, Centre Hospitalier Universitaire de Nancy, Vandoeuvre-lès-Nancy, France;
authors.forename: Luc
authors.initials: L
authors.lastname: Frimat
authors.affiliation: Department of Nephrology, Humber River Regional Hospital and University of Toronto, Weston, Ontario, Canada; and.
authors.forename: David C
authors.initials: DC
authors.lastname: Mendelssohn
authors.affiliation: Arbor Research Collaborative for Health, Ann Arbor, Michigan;
authors.forename: Friedrich K
authors.initials: FK
authors.lastname: Port
authors.affiliation: Arbor Research Collaborative for Health, Ann Arbor, Michigan;
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Pisoni
authors.affiliation: Arbor Research Collaborative for Health, Ann Arbor, Michigan; Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan.
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Robinson
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D057966:Calcimimetic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000069449:Cinacalcet; D019587:Dietary Supplements / Q000009:adverse effects; D005260:Female; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000097:blood / Q000175:diagnosis / Q000209:etiology / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009281:Naphthalenes / Q000009:adverse effects / Q000627:therapeutic use*; D010281:Parathyroid Hormone / Q000097:blood; D016105:Parathyroidectomy / Q000009:adverse effects / Q000401:mortality / Q000639:trends*; D011446:Prospective Studies; D006435:Renal Dialysis / Q000009:adverse effects* / Q000401:mortality; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D015854:Up-Regulation; D014807:Vitamin D / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D015415:Biomarkers; D057966:Calcimimetic Agents; D009281:Naphthalenes; C470125:PTH protein, human; D010281:Parathyroid Hormone; D014807:Vitamin D; D000069449:Cinacalcet
keywords: CKD; ESRD; dialysis; hyperparathyroidism; parathyroid hormone