Paricalcitol in Reducing Parathyroid Hormone Levels and Ameliorating Markers of Bone Remodelling in Renal Transplant Recipients With Secondary Hyperparathyroidism
Paricalcitol in Reducing Parathyroid Hormone Levels and Ameliorating Markers of Bone Remodelling in Renal Transplant Recipients With Secondary Hyperparathyroidism
The risk of fracture for kidney transplant recipients is 4 times higher that of the general
 population. The hyperparathyroidism plays a key role in the maintenance or development of
 post-transplant alterations of bone remodelling.

 Renal transplant patients are at high risk of hyperparathyroidism, largely because of
 long-lasting renal insufficiency before transplant, and of progressive deterioration of
 kidney function because of chronic allograft nephropathy (a disease of proteinuria and
 progressive decline of the glomerular filtration rate).In hemodialysis patients, intravenous
 paricalcitol (19-nor-1,25-dihydroxyvitamin D2), a new vitamin D analogue, achieves a faster
 and more effective normalization of parathyroid hormone (PTH) levels than calcitriol
 (1,25-dihydroxyvitamin D3), an effect that is associated with smaller changes in serum
 calcium and phosphorus levels.

 Whether oral paricalcitol may help achieving a prompt reduction in serum PTH levels and,
 secondarily, in urinary protein excretion in renal transplant recipients with secondary
 hyperparathyroidism is worth investigating.
BACKGROUND The risk of fracture for kidney transplant recipients is 4 times higher that of
 the general population. The pathogenesis of post-transplant bone disease is multifactorial,
 but hyperparathyroidism plays a key role in the maintenance or development of post-transplant
 alterations of bone remodelling. Vitamin D and its analogues are key components of treatment
 aimed to prevent or ameliorate secondary hyperparathyroidism in patients with chronic kidney
 disease (CKD). In hemodialysis patients, intravenous paricalcitol
 (19-nor-1,25-dihydroxyvitamin D2), a new vitamin D analogue, achieves a faster and more
 effective normalization of parathyroid hormone (PTH) levels than calcitriol
 (1,25-dihydroxyvitamin D3), an effect that is associated with smaller changes in serum
 calcium and phosphorus levels. Preliminary evidence is also available that in pre-dialysis
 patients with CKD and secondary hyperparathyroidism, treatment with oral paricalcitol may
 also reduce urinary protein excretion, an effect that is independent of concomitant treatment
 with agents that block the renin-angiotensin system and that in the long-term might translate
 into slower progression to end stage kidney disease and need for renal replacement therapy.

 Renal transplant patients are at high risk of hyperparathyroidism, largely because of
 long-lasting renal insufficiency before transplant, and of progressive deterioration of
 kidney function because of chronic allograft nephropathy (a disease of proteinuria and
 progressive decline of the glomerular filtration rate). Whether oral paricalcitol may help
 achieving a prompt reduction in serum PTH levels and, secondarily, in urinary protein
 excretion in renal transplant recipients with secondary hyperparathyroidism is worth
 investigating.

 AIMS Primary To evaluate whether 6-months treatment with paricalcitol may achieve a prompt
 and effective reduction in PTH serum levels in stable renal transplant patients with
 secondary hyperparathyroidism.

 DESIGN This will be a Prospective, Randomized, Open label, Cross-over study of 6-months with
 Paricalcitol or standard treatment for hyperparathyroidism.

 After one month wash-out from any form of Vitamin D therapy, patients satisfying the
 inclusion/exclusion criteria will be randomized to two treatment arms:

 1. Paricalcitol capsules 1- 2 mcg/day/pts for 26 weeks

 2. Standard therapy for hyperparathyroidism for 26 weeks At the end of the first treatment
 period with Paricalcitol or Standard therapy each patient will cross-over to the other
 treatment.

 After baseline evaluation eligible patients will enter a 6 months treatment period whit oral
 paricalcitol (1-2 mcg/day), or standard treatment for hyperparathyroidism, added-on
 background therapy whit calcium and phosphate supplementation as deemed clinically
 appropriate.
Inclusion Criteria:

 -  Males and females >18 years old

 -  Renal transplant recipients with persistent secondary hyperparathyroidism

 -  PTH persistently >80 pg/mL up 2 month post transplant (stable or progressively
 increasing PTH levels)

 -  No ongoing therapy with Vitamin D

 -  Patients on maintenance therapy with calcineurin inhibitors and Mycophenolate Mofetil
 or Azathioprine

 -  Serum creatinine < 2mg/dL

 -  Patients legally able to give written informed consent to the trial (signed and dated
 by the patient)

 -  Written informed consent.

 Exclusion Criteria:

 -  Concomitant administration of other forms of Vitamin D (different from paricalcitol)

 -  PTH< 80 pg/ml

 -  Serum Ca> 10,2 mg/dL

 -  Clinically serious condition

 -  History of malignancy

 -  Evidence of active hepatitis C virus, hepatitis B virus or human acquired
 immunodeficiency virus infection

 -  Specific contraindications or history of hypersensitivity to the study drugs;

 -  Previous history of allergy or intolerance, or evidence of immunologically-mediated
 renal disease, systemic diseases, cancer

 -  Drug or alcohol abuse

 -  Any chronic clinical conditions that may affect completion of the trial or confound
 data interpretation

 -  Pregnancy or lactating

 -  Women of childbearing potential without following a scientifically accepted form of
 contraception

 -  Legal incapacity

 -  Evidence of an uncooperative attitude

 -  Any evidence that patient will not be able to complete the trial follow-up.

 -  Previous diagnosis of: intellectual disability/mental retardation, dementia,
 schizophrenia.