Mineral Metabolism and Vascular Effects of Vitamin D Therapy in Kidney Transplant Patients (PAD)

Emory University

Status and phase

Terminated

Phase 4

Conditions

Hyperparathyroidism, Secondary

Treatments

Drug: doxercalciferol

Study type

Interventional

Funder types

Other

Identifiers

NCT00646282

IRB00006614

Details and patient eligibility

About

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.

Full description

The investigators plan to study the cardiovascular and bone effects of Hectorol® in 100 kidney transplant recipients. The kidney transplant patients will be screened for kidney transplant dysfunction and hyperparathyroidism. The study medication will be given to 50 patients. The other 50 patients will continue to be treated with the actual standard of care at the transplant clinic. Subjects will be followed for 18 months and their laboratory values, bone density, vascular calcification and stiffness will be collected to see if there is an effect of Hectorol® compared to the actual standard of care.

Enrollment

12 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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