Doxercalciferol safely suppresses PTH levels in patients with secondary hyperparathyroidism associated with chronic kidney disease stages 3 and 4.
BACKGROUND
Calcitriol lowers parathyroid hormone (PTH) levels in patients with chronic kidney disease (CKD) stages 3 and 4, but its use is limited by a low therapeutic index and concerns regarding hypercalcemia and acceleration of kidney disease. We evaluated doxercalciferol (1alpha-hydroxyvitamin D2) as an alternative therapy in a randomized, double-blinded, placebo-controlled, multicenter trial.


METHODS
Fifty-five adults with stage 3 or 4 CKD and an intact PTH (iPTH) level greater than 85 pg/mL (ng/L) completed 8 baseline weeks, followed by 24 weeks of oral therapy with doxercalciferol or placebo. Pretreatment demographics and biochemical features did not differ between groups. Dosages were increased gradually if iPTH level was not decreased by 30% or greater and serum calcium and phosphorus levels were stable. Regular monitoring included plasma iPTH, serum calcium and phosphorus, urinary calcium, bone-specific serum markers, and serum lalpha,25-dihydroxyvitamin D levels. Glomerular filtration rate (GFR) was measured before and after treatment.


RESULTS
Mean plasma iPTH level decreased by 46% from baseline after 24 weeks of doxercalciferol treatment (P <0.001), but was unchanged with placebo. After 6 weeks, iPTH level reductions with doxercalciferol treatment exceeded those with placebo at all subsequent intervals (P <0.001). No clinically significant differences in mean serum calcium or phosphorus or urinary calcium levels or incidence of hypercalcemia, hyperphosphatemia, or hypercalciuria were noted between groups. Serum C- and N-telopeptide and bone-specific alkaline phosphatase levels decreased with doxercalciferol treatment relative to both baseline and placebo (P <0.01). Adverse-event rates and changes in GFR did not differ between groups.


CONCLUSIONS
Doxercalciferol is safe and effective in controlling secondary hyperparathyroidism of patients with CKD stages 3 and 4.
Coburn
Jack W
JW
West Los Angeles Veterans Affairs Healthcare Center, Los Angeles, CA 90073, USA. jack.coburn@med.va.gov
Maung
Hla M
HM
Elangovan
Logan
L
Germain
Michael J
MJ
Lindberg
Jill S
JS
Sprague
Stuart M
SM
Williams
Mark E
ME
Bishop
Charles W
CW
D000368:Aged; D002118:Calcium / Q000097:blood / Q000652:urine; D002908:Chronic Disease; D004311:Double-Blind Method; D004872:Ergocalciferols / Q000627:therapeutic use*; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000188:drug therapy* / Q000209:etiology*; D007674:Kidney Diseases / Q000150:complications* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood*; D010758:Phosphorus / Q000097:blood
D004872:Ergocalciferols; D010281:Parathyroid Hormone; D010758:Phosphorus; C042533:1 alpha-hydroxyergocalciferol; D002118:Calcium