Effects of Cinacalcet in Renal Transplant Patients with Hyperparathyroidism
ABSTRACT Cinacalcet decreases serum parathyroid hormone (PTH) and calcium concentrations in kidney transplant recipients with autonomous hyperparathyroidism. Long-term treatment with cinacalcet may increase urinary calcium excretion and the risk of renal calcium deposits and may alter renal graft function.
We studied 71 renal recipients with hypercalcemic hyperparathyroidism. Of these patients, 34 received cinacalcet between month 3 and month 12 after renal transplantation. We compared phosphate calcium balance, measured glomerular filtration rate (GFR) and renal biopsies in cinacalcet-treated and non-cinacalcet-treated patients. Measurements were performed before initiating cinacalcet treatment (month 3) and at month 12.
Patients treated with cinacalcet had more severe hyperparathyroidism. Serum PTH concentration decreased in both groups between months 3 and 12, but the decrease was much more important in cinacalcet-treated patients. Urinary calcium excretion significantly increased under cinacalcet treatment and was more than twice as high at month 12 as in patients who did not receive cinacalcet treatment. However, the hypercalciuria was not associated with an increase in calcium deposits on renal biopsies or an alteration of measured GFR.
Despite sustained and marked hypercalciuria induced by cinacalcet treatment, cinacalcet does not have adverse effects on GFR or on renal graft calcium deposits in the first year following renal transplantation.
01/2015; 2015:1-12. DOI:10.1155/2015/292654
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ABSTRACT: The effects of pre-transplantation medication for secondary hyperparathyroidism on post-transplantation parathyroid hormone (PTH) and calcium levels have not yet been conclusively determined. Therefore, this study sought to determine the level of off-label use of cinacalcet and to determine predictors of its administration during the long-term follow-up of a cohort of individuals who received deceased-donor renal transplants. Furthermore, safety considerations concerning the off-label use of cinacalcet are addressed. This was a case-control study of 355 stable renal transplant recipients. The patient cohort was divided into two groups. Transplant group A comprised patients who did not receive cinacalcet treatment, and transplant group B comprised patients who received cinacalcet treatment during follow-up after renal transplantation. The characteristics of the patients were evaluated to determine predictors of cinacalcet use after successful renal transplantation. Compared with the control individuals (n = 300), the cinacalcet-treated individuals (n = 55) had significantly higher PTH levels at 4 weeks post-transplantation (20.3 ± 1.6 versus 40.7 ± 4.0 pmol/L, p = 0.0000) when they were drug naive. At 3.2 years post-transplantation, cinacalcet-treated patients showed higher PTH (26.2 ± 2.3 versus 18.4 ± 2.3 pmol/L, p = 0.0000), higher calcium (2.42 ± 0.03 versus 2.33 ± 0.01 mmol/L, p = 0.0045) and lower phosphate (0.95 ± 0.04 versus 1.06 ± 0.17 mmol/L, p = 0.0021) levels. Individuals in the verum group were more likely to receive cinacalcet therapy (45.5% versus 14.3%, p = 0.0000), and they had higher pill burdens for the treatment of hyperparathyroidism (1.40 ± 0.08 versus 0.72 ± 0.03 pills per patient, p = 0.0000) whilst they were on the waiting list for transplantation. Regression analysis confirmed the associations between hypercalcaemic hyperparathyroidism and PTH levels at 4 weeks post-transplantation (p = 0.0001), cinacalcet use (p = 0.0000) and the preoperative total pill burden (p = 0.0000). Renal function was the same in both groups. Parathyroid gland dysfunction pre-transplantation translates into clinically relevant hyperparathyroidism post-transplantation, despite patients being administered more intensive treatment whilst on dialysis. PTH levels at 4 weeks post-transplantation might serve as a marker for the occurrence of hypercalcaemic hyperparathyroidism during follow-up.12/2014; 3(1):21. DOI:10.1186/s13737-014-0021-5
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ABSTRACT: The calcium sensing receptor (CaSR) has played an important role as a target in the treatment of a variety of disease states over the last 20 plus years. In this review, we give an overview of the receptor at the cellular level and then provide details as to how this receptor has been targeted to modulate cellular ion transport mechanisms. As a member of the G protein-coupled receptors family, it has a high degree of homology with a variety of other members in this class, which could explain why this receptor has been identified in so many different tissues throughout the body. This diversity of locations throughout the body sets it apart from other members of the family, and may explain how the receptor interacts with so many different organ systems in the body to modulate the physiology and pathophysiology. The receptor is unique in that it has two large exofacial lobes that sit in the extracellular environment and sense changes in a wide variety of environmental cues including: salinity, pH, amino acids concentration, polyamines to name just a few. It is for this reason that there has been a great deal of research associated with normal receptor physiology over the last 20 years. With the ongoing research in more recent years a focus on the pathophysiology has emerged and the effects of receptor mutations on cellular and organ physiology. We hope that this review will enhance and update the knowledge about the importance of this receptor and stimulate future potential investigations focused around this receptor in cellular, organ, and systemic physiology and pathophysiology.AJP Cell Physiology 05/2014; 307(3). DOI:10.1152/ajpcell.00139.2014 · 3.67 Impact Factor