Vitamin D and cinacalcet administration pre-transplantation predict hypercalcaemic hyperparathyroidism post-transplantation: a case-control study of 355 deceased-donor renal transplant recipients over 3 years

Abstract

BackgroundThe 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.MethodsThis 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.ResultsCompared 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.ConclusionsParathyroid 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.

Causes of hypercalcemia in renal transplant recipients: persistent hyperparathyroidism and others

“…Hypophosphatemia is very common after KTx and has been reported in 40-90% of patients in the early period following transplantation ( 16 ). KTx induces specific changes in phosphate metabolism.…”

Persistent Hyperparathyroidism Post- Kidney Transplantation: A Single Center Experience

“…The cause of persistent HPT is partly due to persistence of structural changes in the parathyroid glands, such as hyperplasia and adenoma formation, despite removal of the initial stimuli for HPT [5], [6].…”

Modern approaches to correction mineral and bone disorders in kidney transplant recipients

“…Алгоритм коррекции гиперкальциемии цинакальцетом у реципиентов почечного трансплантата с посттранс-плантационным ГПТ [25] Fig. The correction of hypercalcemia by cinacalcet in renal transplant recipients with hyperparathyroidism [25] циурию, снижение функции почки является отно-сительно небольшим и временным, проходящим после его отмены, что обусловлено сдвигами в почечной гемодинамике, а не структурными нару-шениями, препарат не оказывает негативного воз-действия на проводимую иммуносупрессивную те-рапию [16,20,23,24]. Тем не менее вопрос о возможности и длитель-ности назначения препарата при гиперкальциемии, обусловленной посттрансплантационным ГПТ, ос-тается открытым.…”

“…Обосновывая пока-зания к ПТЭ, учитывают определенные нарушения со стороны минерального и костного метаболизма (высокий уровень ПТГ, прогрессирующее сниже-ние минеральной костной массы/костные перело-мы, гиперкальциемия и др. ), а также сложившуюся в данном центре реальную клиническую практику [15,24,40].…”