Mineral Metabolism and Vascular Effects of Vitamin D Therapy in Kidney Transplant Patients
Condition: Hyperparathyroidism, Secondary
MeSH terms: Hyperparathyroidism; Hyperparathyroidism, Secondary
Intervention: doxercalciferol
Intervention description: The study drug dosage will be initiated according to baseline iPTH levels. For patients with iPTH>300 pg/ml, oral Doxercalciferol will be given at 1 mcg/day; for patients with iPTH <300 pg/ml, oral Doxercalciferol will be initiated at 0.5 mcg/day.
Intervention MeSH terms: 1 alpha-hydroxyergocalciferol
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 12.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Patients with kidney failure on dialysis can be successfully transplanted. However, many of
      them do not attain a normal kidney function and/or present a slow deterioration of kidney
      function after transplantation. As a consequence, they can develop an endocrine disorder
      called hyperparathyroidism, which can cause bone disease and a high risk of bone fractures.
      In spite of the known bone disease and hyperparathyroidism, there is no well defined
      treatment for these patients.

      Moreover, kidney transplant recipients present a higher mortality rate compared to the
      general population, and the principal cause of death is cardiovascular disease. Dialysis
      patients are known to have extensive cardiovascular calcifications and increased vascular
      stiffness, and these factors have been closely associated with cardiovascular mortality.

      The effect of vitamin D on bone health is well known in the general population. Many studies
      showed a reduction in fracture rate in post-menopausal women and older men receiving vitamin
      D and calcium supplements. Vitamin D analogues are also commonly used to treat
      hyperparathyroidism in dialysis patients. Finally, vitamin D has been suggested to have
      beneficial effects on the cardiovascular system and to reduce mortality in dialysis patients.

      Hectorol® is a vitamin D analog which has been demonstrated to effectively treat
      hyperparathyroidism in dialysis and pre-dialysis patients.

      The effects of vitamin D supplementation on bone disease, hyperparathyroidism and
      cardiovascular function in kidney transplant recipients have not been properly studied.

      Whether Hectorol® therapy helps reducing the severity of bone disease and improving vascular
      function in kidney transplant recipients is still unknown.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Kidney transplant recipient > 18 year/old with reduced and stable kidney function
             (estimated GFR 25-60 ml/min/1.73m2)

          -  iPTH levels between 120 and 500 pg/ml

          -  Stable immunosuppressive therapy (5-10 mg Prednisone/day, stable dosage of calcineurin
             inhibitors, or other immunosuppressive agents for at least 6 months)

        Exclusion Criteria:

          -  Recent rejection episode (< 3 months)

          -  One of the following: baseline estimated GFR>60 ml/min/1.73m2 or <25 ml/min/1.73m2,
             albumin-corrected Ca>9.5 mg/dl or serum phosphorus >4.6 mg/dl.

          -  Recipients of dual transplant organs with exception of kidney-pancreas

          -  Patients already receiving treatment with Vitamin D analogues

          -  Severe peripheral vascular disease or coronary artery disease

          -  History of previous parathyroidectomy

          -  Current alcohol or drug abuse

          -  Pregnant or nursing woman or female of child-bearing age not receiving contraception

          -  Other comorbidities that in the opinion of the investigators would reduce expected
             patient's survival and preclude study completion

          -  Medications that could interfere with Hectorol® metabolism