title: A randomized multicenter trial of paricalcitol versus calcitriol for secondary hyperparathyroidism in stages 3-4 CKD.
abstract: OBJECTIVE
  Calcitriol is used to treat secondary hyperparathyroidism in patients with CKD. Paricalcitol is less calcemic and phosphatemic in preclinical studies and in some trials in dialysis patients, but head-to-head comparisons in nondialysis patients are lacking. A large meta-analysis of trials concluded that these agents did not consistently reduce parathyroid hormone (PTH) and increased the risk of hypercalcemia and hyperphosphatemia. Therefore, the objective of this multicenter trial was to compare the rate of hypercalcemia between calcitriol and paricalcitol, while suppressing PTH 40%-60%.
  
  
  METHODS
  Patients with stages 3-4 CKD (n=110) with a PTH level >120 pg/ml were recruited and randomized to 0.25 μg/d of calcitriol or 1 μg/d of paricalcitol between April 2009 and July 2011. Subsequent dose adjustments were by protocol to achieve 40%-60% PTH suppression below baseline. The primary endpoint was the rate of confirmed hypercalcemia of >10.5 mg/dl between groups.
  
  
  RESULTS
  Forty-five patients in each group completed the 24 weeks of treatment. Both agents suppressed PTH effectively (-52% with paricalcitol and -46% with calcitriol; P=0.17), although the paricalcitol group reached a 40% reduction in PTH sooner at a median 8 weeks (interquartile range [IQR], 4, 12) versus 12 weeks (IQR, 8, 18; P=0.02) and had a lower pill burden of 240 (IQR, 180, 298) versus 292 (IQR, 231, 405; P=0.01). Confirmed hypercalcemia was very low in both groups (three with paricalcitol and one with calcitriol) and was not significantly different (P=0.36). Both groups had small increases in calcium and phosphorus levels (0.3-0.4 mg/dl in each electrolyte) and significant decreases in alkaline phosphatase, a marker of high bone turnover, with no significant differences between groups.
  
  
  CONCLUSIONS
  These results show that both calcitriol and paricalcitol achieved sustained PTH and alkaline phosphatase suppression in stages 3-4 CKD, with small effects on serum calcium and phosphorus and a low incidence of hypercalcemia.
authors: Renal Division, School of Medicine, Washington University, St. Louis, Missouri; DCoyne@dom.wustl.edu.
authors: Daniel W
authors: DW
authors: Coyne
authors: Renal Division, School of Medicine, Washington University, St. Louis, Missouri;
authors: Seth
authors: S
authors: Goldberg
authors: Division of Nephrology and Hypertension, Henry Ford Hospital, Detroit, Michigan;
authors: Mark
authors: M
authors: Faber
authors: Divison of Nephrology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois; and.
authors: Cybele
authors: C
authors: Ghossein
authors: Division of nephrology and Hypertension, Northshore University Health System, University of Chicago Pritzker School of Medicine, Evanston, Illinois.
authors: Stuart M
authors: SM
authors: Sprague
mesh_terms: D000368:Aged; D002117:Calcitriol / Q000627:therapeutic use*; D004872:Ergocalciferols / Q000627:therapeutic use*; D006801:Humans; D006934:Hypercalcemia / Q000139:chemically induced / Q000453:epidemiology; D006962:Hyperparathyroidism, Secondary / Q000188:drug therapy* / Q000209:etiology; D015994:Incidence; D007676:Kidney Failure, Chronic / Q000150:complications; D008875:Middle Aged
chemical_list: D004872:Ergocalciferols; C084656:paricalcitol; D002117:Calcitriol
keywords: calcium; chronic renal disease; hyperparathyroidism; vitamin D