title: Low-dose cholecalciferol supplementation and dual vitamin D therapy in haemodialysis patients.
abstract: BACKGROUND
  Traditionally, secondary hyperparathyroidism (SHPT) due to low calcitriol synthesis in failing kidneys has been treated with synthetic vitamin D receptor (VDR) activators. Recently, also the importance of low native vitamin D status beyond the issue of SHPT has been recognized in these patients. The aim of this work was to evaluate the effect of cholecalciferol supplementation in haemodialysis patients with low vitamin D serum levels. Another aim was to evaluate dual vitamin D therapy (cholecalciferol supplementation plus paricalcitol) in haemodialysis patients with vitamin D deficiency and concomitant SHPT.
  
  
  METHODS
  Ninety clinically stable maintenance haemodialysis patients were included. Supervised cholecalciferol supplementation was administered due to low vitamin D status. Patients with SHPT were also treated with synthetic VDR activator. Two pre hoc subgroups for statistical analysis were formed: patients treated solely with cholecalciferol (N=34; 5,000 IU once weekly) and patients treated with a combination of cholecalciferol (identical dose, i.e. 5,000 IU/week) plus paricalcitol (N=34, median dose 10 μg/week). Follow-up visit was scheduled 15 weeks later. Serum concentrations of calcidiol (25-D), parathyroid hormone (PTH) and beta-cross laps (CTX) were assessed at baseline and at follow-up. Serum calcium, phosphate and alkaline phosphatase (ALP) were monitored monthly. Only non-calcium gastrointestinal phosphate binders were administered. Dialysate calcium was 1.5 mmol/L in all patients, and no oral calcium-containing preparations were prescribed. Depending on data distribution, parametric or nonparametric statistical methods were used for comparison within each group (i.e. baseline vs. follow-up data) as well as between groups.
  
  
  RESULTS
  In the whole group of 90 patients, mean baseline 25-D serum level was 20.3 (standard deviation 8.7) nmol/L, and it increased to 66.8 (19) nmol/L (p<0.0001) after supplementation. In both preformed subgroups, the effect of vitamin D supplementation was almost identical. In cholecalciferol monotherapy, 25-D levels increased from 18.4 (8.2) to 68.6 (21.2) and in dual vitamin D therapy from 18.4 (5.0) to 67.6 (17.7) nmol/L (both p<0.0001). In addition, both treatment modalities decreased serum PTH levels importantly: from 21.7 (interquartile range 17.3; 35.4) to 18.1 pmol/L (15.3; 24.7) in monotherapy (p=0.05) and from 38.6 (31.8; 53.3) to 33.9 pmol/L (26.1; 47.5) in dual vitamin D therapy (p=0.01). Serum calcium, phosphate, ALP and CTX did not change. We have not observed any episode of hypercalcemia in any subject during the whole period of follow-up. At baseline, slightly lower 25-D levels were observed in diabetic than in non-diabetic patients. This difference disappeared after substitution. Vitamin D status and its changes were not related to the patient's age.
  
  
  CONCLUSIONS
  Low 25-D levels were very common in haemodialysis patients. They were safely and effectively corrected with supervised low-dose cholecalciferol supplementation. In patients with higher baseline PTH levels, dual vitamin D therapy (cholecalciferol plus paricalcitol) was safely and effectively used.
authors.affiliation: Haemodialysis Centre, University Hospital Hradec Kralove, Sokolská 581, 500 05, Hradec Kralove, Czech Republic, sulkovas@gmail.com.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Dusilová-Sulková
authors.forename: Roman
authors.initials: R
authors.lastname: Šafránek
authors.forename: Jaroslava
authors.initials: J
authors.lastname: Vávrová
authors.forename: Jiří
authors.initials: J
authors.lastname: Horáček
authors.forename: Ladislava
authors.initials: L
authors.lastname: Pavlíková
authors.forename: Vladimír
authors.initials: V
authors.lastname: Palička
mesh_terms: D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D002112:Calcifediol / Q000097:blood; D002118:Calcium / Q000097:blood; D002762:Cholecalciferol / Q000008:administration & dosage*; D019587:Dietary Supplements; D004359:Drug Therapy, Combination; D004872:Ergocalciferols / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000097:blood / Q000188:drug therapy*; D007676:Kidney Failure, Chronic / Q000150:complications / Q000628:therapy; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood; D010710:Phosphates / Q000097:blood; D018167:Receptors, Calcitriol / Q000819:agonists; D006435:Renal Dialysis; D014808:Vitamin D Deficiency / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D014815:Vitamins / Q000008:administration & dosage*
chemical_list: D050071:Bone Density Conservation Agents; D004872:Ergocalciferols; D010281:Parathyroid Hormone; D010710:Phosphates; D018167:Receptors, Calcitriol; D014815:Vitamins; D002762:Cholecalciferol; C084656:paricalcitol; D000469:Alkaline Phosphatase; D002112:Calcifediol; D002118:Calcium