The calcimimetic cinacalcet normalizes serum calcium in renal transplant patients with persistent hyperparathyroidism

Kruse, Anja; Eisenberger, Ute; Frey, Felix J.; Mohaupt, Markus

doi:10.1093/ndt/gfh924

Cited by 156 publications

(107 citation statements)

References 18 publications

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“…Calcimimetics inhibit PTH secretion by modulating the calcium-sensing receptor in the parathyroid gland and could represent an alternative approach in these patients. In a recent study, 30 mg/d cinacalcet for 3 mo normalized the serum calcium in all but two patients, whereas serum PTH and phosphate levels did not change significantly (80). Similarly, Serra et al (81) showed in a short study of 10 wk duration that cinacalcet was effective in correcting the hypercalcemia and reducing PTH values in patients who received a transplant and had persistent hyperparathyroidism.…”

Section: Role Of Calcimimeticsmentioning

confidence: 84%

Bone Disease after Renal Transplantation

Weisinger¹,

Carlini²,

Rojas³

et al. 2006

Clinical Journal of the American Society of Nephrology

125

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It has been well established that a rapid decrease in bone mineral density (BMD) occurs in the first 6 to 12 mo after a successful renal transplantation and persists, albeit at a lower rate, for many years. This rapid BMD loss significantly increases the fracture risk of these patients to levels that are even higher than those of patients who have chronic kidney disease stage 5 and are on dialysis. The presence of low BMD in renal transplant patients as a predictor of risk fracture is controversial. Indeed, as has been suggested also for patients with postmenopausal osteoporosis, there is not a compelling correlation between the decline in BMD and skeletal fractures. However, bone disease after renal transplantation probably represents a unique bone disorder that must encompass underlying renal osteodystrophy. In fact, this syndrome results from multiple factors that include pretransplantation bone status, use of glucocorticoids and other immunosuppressive drugs, hypophosphatemia, and alterations of the calcium-vitamin D axis. Recent studies have demonstrated decreased osteoblast number, reduced bone formation rate, delayed mineralization, and increased osteoblast and osteocyte apoptosis. Bisphosphonates and vitamin D metabolites may be valuable in preventing or diminishing early bone loss. However, clinicians should be careful with the use of bisphosphonates and oversuppression of bone, especially in patients with low bone turnover. New prospective, controlled trials are required to confirm the real efficacy of these drugs, particularly in long-term renal transplant patients.Clin J Am Soc Nephrol 1: 1300 -1313, 2006. doi: 10.2215/CJN.01510506 K idney, heart, lung, and liver transplantation have become fairly common and successful. As the number of transplants has grown, new challenges have arisen in the management of long-term complications of transplantation. Posttransplantation bone disease represents one such important complication, because it is observed in a substantial proportion of patients. As a consequence, bone mass loss and bone fractures are common in these patients and cause substantial morbidity.In patients with chronic kidney disease (CKD), renal osteodystrophy that begins during the early stages of the disease usually worsens during dialysis and may persist after transplantation, although in many patients, improvement in these bone lesions are observed. In addition to preexisting bone lesions, not only factors that hamper recovery but also new factors could affect bone structure after transplantation. These include the potential deleterious effects on bone of the different immunosuppressive agents, the impaired renal function that frequently is observed in renal transplant patients, and several others factors that are particular to each patient, such as postmenopausal status, presence of diabetes, gender, and time after transplantation. Changes in Bone Mineral DensityBone mineral density (BMD) as assessed by dual x-ray absorptiometry has been used as a noninvasive method to assess bone mass loss...

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Section: Role Of Calcimimeticsmentioning

confidence: 84%

Bone Disease after Renal Transplantation

Weisinger¹,

Carlini²,

Rojas³

et al. 2006

Clinical Journal of the American Society of Nephrology

125

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“…More recently, cinacalcet has been used in KTx recipients (5,6). Kruse et al (5) reported successful reduction in SCa levels in 14 KTx recipients with persistent HPT after TX. They did not see, however, a statistically significant decrease in PTH levels (5).…”

Section: Discussionmentioning

confidence: 99%

“…We report herein our experience with cinacalcet in the management of persistent HPT and hypercalcemia after KTx. We also compare and contrast our experience with the recently published experience of two other groups that have used cinacalcet in a similar manner (5,6).…”

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confidence: 95%

Improvement in Hypercalcemia with Cinacalcet after Kidney Transplantation

Srinivas¹,

Schold²,

Womer³

et al. 2006

Clinical Journal of the American Society of Nephrology

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Cinacalcet, a calcimimetic, was evaluated in persistent hyperparathyroidism after kidney transplantation (Tx). Ten kidney transplant recipients and one kidney-pancreas recipient with persistent post-Tx hypercalcemia (serum calcium [SCa] > 10.2 mg/dl), stable graft function, and intact parathyroid hormone (iPTH) >2 times normal received 30 mg/d cinacalcet between 2 mo and 5 yr after Tx. SCa, serum phosphorus (SP), and iPTH were measured before and after cinacalcet. Mean pre-cinacalcet SCa was 10.9 mg/dl (8.6 to 11.9 mg/dl). Average pre-cinacalcet SP was 2.9 mg/dl (1.8 to 4.0 mg/dl). Mean pre-cinacalcet iPTH was 267.0 pg/ml (99 to 723 pg/ml). After cinacalcet, SCa decreased on average by 1.6 mg/dl (95% confidence interval 1.2 to 2.1; P < 0.0001). Post-cinacalcet SP increased on average 0.45 mg/dl (P ‫؍‬ 0.046). Post-cinacalcet iPTH averaged 156.9 mg/dl (P ‫؍‬ 0.10). Graft function remained stable. Cinacalcet lowers SCa and raises SP in the short term in patients with persistent post-Tx hyperparathyroidism; long-term bone effects and persistent hyperparathyroidism merit further study.Clin J Am Soc Nephrol 1: 323-326, 2006323-326, . doi: 10.2215 H ypercalcemia is a frequent complication that ensues after successful kidney transplantation (KTx) (1). Persistent hyperparathyroidism (HPT) is the most frequent cause of post-KTx hypercalcemia (1). The usual management of hypercalcemia after KTx involves a period of conservative management followed by parathyroidectomy in cases with unremitting hypercalcemia Ͼ6 to 12 mo after KTx (1). In recent years, intravenous vitamin D 3 and other vitamin D analogs have been used in dialysis patients to suppress parathyroid hormone (PTH) levels (2). After successful KTx, these agents are discontinued abruptly, followed by an increase in PTH levels, a change in the known natural history of HPT attendant to renal failure. Recently, the calcimimetic agent cinacalcet was approved to treat the HPT that accompanies renal failure (3,4). We hypothesized that cinacalcet may be effective in lowering serum calcium (SCa) and PTH levels in some patients with persistent post-KTx hypercalcemia. We report herein our experience with cinacalcet in the management of persistent HPT and hypercalcemia after KTx. We also compare and contrast our experience with the recently published experience of two other groups that have used cinacalcet in a similar manner (5,6). Materials and MethodsThis study is a retrospective review of the clinical experience with cinacalcet at the University of Florida Kidney Transplant Program. Ten KTx patients (nine deceased donor, two living donor; six male, five female) and one simultaneous kidney-pancreas Tx patient with stable renal allograft function and persistent hypercalcemia after KTx (SCa Ͼ10.2 mg/dl), intact PTH (iPTH) greater than twice the upper limit of normal and stable graft function were started on a single daily oral dose of 30 mg cinacalcet. Cinacalcet was started between 2 mo and 5 yr (median 3 yr) after KTx. We measured SCa, phosphorus (P), and iPTH before and...

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“…Cinacalcet (Sensipar 1 / Mimpara 1 ; Amgen Inc., Thousand Oaks, CA), an allosteric modulator of the CaSR, has demonstrated efficacy in decreasing calcium and PTH in patients with secondary HPT on dialysis (21); and in a number of small, open-label, single arm, single-center and retrospective studies, cinacalcet decreased serum calcium and PTH and increased serum phosphorus levels in renal transplant recipients with persistent HPT (22)(23)(24)(25)(26)(27)(28). In these studies, cinacalcet was well tolerated with no evidence of adverse effects on immunosuppressive therapy or allograft function.…”

Section: Introductionmentioning

confidence: 99%

A Randomized Study Evaluating Cinacalcet to Treat Hypercalcemia in Renal Transplant Recipients With Persistent Hyperparathyroidism

Evenepoel

Cooper

Holdaas

et al. 2014

American Journal of Transplantation

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Persistent hyperparathyroidism (HPT) after kidney transplantation (KTx) is associated with hypercalcemia, hypophosphatemia and abnormally high levels of parathyroid hormone (PTH). In this randomized trial, cinacalcet was compared to placebo for the treatment of hypercalcemia in adult patients with persistent HPT after KTx. Subjects were randomized 1:1 to cinacalcet or placebo with randomization stratified by baseline corrected total serum calcium levels ( 11.2 mg/dL [2.80 mmol/L] or >11.2 mg/dL [2.80 mmol/L]). The primary end point was achievement of a mean corrected total serum calcium value <10.2 mg/dL (2.55 mmol/L) during the efficacy period. The two key secondary end points were percent change in bone mineral density (BMD) at the femoral neck and absolute change in phosphorus; 78.9% cinacalcetversus 3.5% placebo-treated subjects achieved the primary end point with a difference of 75.4% (95% confidence interval [CI]: 63.8, 87.1), p < 0.001. There was no statistical difference in the percent change in BMD at the femoral neck between cinacalcet and placebo groups, p ¼ 0.266. The difference in the change in phosphorus between the two arms was 0.45 mg/dL (95% CI: 0.26, 0.64), p < 0.001 (nominal). No new safety signals were detected. In conclusion, hypercalcemia and hypophosphatemia were effectively corrected after treatment with cinacalcet in patients with persistent HPT after KTx.

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The calcimimetic cinacalcet normalizes serum calcium in renal transplant patients with persistent hyperparathyroidism

Cited by 156 publications

References 18 publications

Bone Disease after Renal Transplantation

Bone Disease after Renal Transplantation

Improvement in Hypercalcemia with Cinacalcet after Kidney Transplantation

A Randomized Study Evaluating Cinacalcet to Treat Hypercalcemia in Renal Transplant Recipients With Persistent Hyperparathyroidism

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