title: VDRA therapy is associated with improved survival in dialysis patients with serum intact PTH ≤ 150 pg/mL: results of the Italian FARO Survey.
abstract: BACKGROUND
  Chronic kidney disease (CKD) patients affected by mineral bone disorders (MBD) have higher rates of all-cause and cardiovascular-related mortality. Approximately, one-third of dialysis patients have low serum parathyroid hormone (PTH) levels (≤ 150 pg/mL). However, the reason why these patients have higher mortality compared to patients with normal PTH levels has not yet been fully elucidated.
  
  
  METHODS
  The FARO study was performed on 2453 Italian patients followed prospectively from 28 dialysis centres over a 2-year period. Data were collected every 6 months and end points included time-to-death cumulative probability in patients with serum intact PTH (iPTH) ≤ 150 pg/mL and the effect of vitamin D receptor activation (VDRA) therapy. Kaplan-Meier curves and proportional hazards regression models stratified by PTH levels (i.e. ≤ 150 and >150 pg/mL) were used to determine cumulative probability of time-to-death and adjusted hazard ratios (HRs) for demographic, clinical and CKD-MBD treatment characteristics.
  
  
  RESULTS
  The cumulative probability of death was higher (P < 0.01) for patients with serum iPTH levels ≤ 150 pg/mL [25.1%, 95% confidence interval (CI): 22.1-28.5 at 18 months] versus those with serum iPTH levels within the normal range (18.0%, 95% CI: 16.1-20.1). In a model with time-dependent covariates restricted to time periods when patients had iPTH levels ≤ 150 pg/mL, lower mortality was observed in patients treated with VDRA [i.e. HR = 0.62, 95% CI: 0.42-0.92 for oral or intravenous (IV) calcitriol; HR = 0.18, 95% CI: 0.04-0.8 for IV paricalcitol] versus those not receiving any VDRA (P < 0.01) independently of other variables. Patients who received IV paricalcitol, compared with either oral or IV calcitriol, showed reduced mortality, but this was not statistically significant (HR = 0.3, 95% CI: 0.07-1.31, P = 0.11).
  
  
  CONCLUSIONS
  Results from this observational study suggest that VDRA therapy was associated with improved survival in dialysis patients, even with low serum iPTH levels.
authors.affiliation: Renal Division, Dipartimento di Medicina, Chirurgia e Odontoiatria, University of Milan, San Paolo Hospital, Milan, Italy. mario.cozzolino@unimi.it
authors.forename: Mario
authors.initials: M
authors.lastname: Cozzolino
authors.forename: Diego
authors.initials: D
authors.lastname: Brancaccio
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Cannella
authors.forename: Piergiorgio
authors.initials: P
authors.lastname: Messa
authors.forename: Loreto
authors.initials: L
authors.lastname: Gesualdo
authors.forename: Martino
authors.initials: M
authors.lastname: Marangella
authors.forename: Cosimo
authors.initials: C
authors.lastname: LoDeserto
authors.forename: Marco
authors.initials: M
authors.lastname: Pozzato
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Rombolà
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Costanzo
authors.forename: Umberto
authors.initials: U
authors.lastname: di Luzio Paparatti
authors.forename: Sandro
authors.initials: S
authors.lastname: Mazzaferro
mesh_terms: D000368:Aged; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D001847:Bone Diseases / Q000150:complications / Q000188:drug therapy / Q000401:mortality; D002113:Calcification, Physiologic / Q000187:drug effects; D004872:Ergocalciferols / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006306:Health Surveys; D006801:Humans; D007676:Kidney Failure, Chronic / Q000209:etiology / Q000401:mortality* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood*; D011379:Prognosis; D011446:Prospective Studies; D018167:Receptors, Calcitriol / Q000378:metabolism*; D006435:Renal Dialysis / Q000401:mortality*; D015996:Survival Rate
chemical_list: D050071:Bone Density Conservation Agents; D004872:Ergocalciferols; D010281:Parathyroid Hormone; D018167:Receptors, Calcitriol; C084656:paricalcitol