Renal allograft failure in a hyperparathyroid patient following initiation of a calcimimetic

Seikrit, Claudia; Mühlfeld, Anja; Groene, Hermann Josef; Floege, Jürgen

doi:10.1038/nrneph.2010.169

Cited by 17 publications

(8 citation statements)

References 22 publications

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“…In a recent case report, calciuria and renal calcifications occurred following treatment with a high dose of cinacalcet (180 mg), however, without any deterioration of allograft function [ 49 ]. In contrast, in two other cases, development of nephrocalcinosis and acute graft failure was reported after cinacalcet was given to kidney transplant recipients with severe forms of hyperparathyroidism at 30 mg [ 50 , 51 ]. The authors hypothesized that treatment with cinacalcet in the immediate posttransplant period, when calcineurin inhibitors and high doses of glucocorticoids enhance bone resorption and calcium excretion, might have contributed to acute renal failure [ 51 ].…”

Section: Discussionmentioning

confidence: 99%

Long-Term Clinical Practice Experience with Cinacalcet for Treatment of Hypercalcemic Hyperparathyroidism after Kidney Transplantation

Thiem

Gessl

Borchhardt

2015

BioMed Research International

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Within this prospective, open-label, self-controlled study, we evaluated the long-term effects of the calcimimetic cinacalcet on calcium and phosphate homeostasis in 44 kidney transplant recipients (KTRs) with hypercalcemic hyperparathyroidism by comparing biochemical parameters of mineral metabolism between pre- and posttreatment periods. Results are described as mean differences (95% CIs) between pre- and posttreatment medians that summarize all repeated measurements of a parameter of interest between the date of initial hypercalcemia and cinacalcet initiation (median of 1.6 (IQR: 0.6–3.8) years) and up to four years after treatment start, respectively. Cinacalcet was initiated after 1.8 (0.8–4.7) years posttransplant and maintained for 6.2 (3.9–7.6) years. It significantly decreased total serum calcium (−0.30 (−0.34 to −0.26) mmol/L, P < 0.001) and parathyroid hormone levels (−79 (−103 to −55) pg/mL, P < 0.001). Serum levels of inorganic phosphate (Pi) and renal tubular reabsorption of phosphate to glomerular filtration rate (TmP/GFR) increased simultaneously (Pi: 0.19 (0.15–0.23) mmol/L, P < 0.001, TmP/GFR: 0.20 (0.16–0.23) mmol/L, P < 0.001). In summary, cinacalcet effectively controlled hypercalcemic hyperparathyroidism in KTRs in the long-term and increased low Pi levels without causing hyperphosphatemia, pointing towards a novel indication for the use of cinacalcet in KTRs.

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Section: Discussionmentioning

confidence: 99%

Long-Term Clinical Practice Experience with Cinacalcet for Treatment of Hypercalcemic Hyperparathyroidism after Kidney Transplantation

Thiem

Gessl

Borchhardt

2015

BioMed Research International

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“…Cinacalcet allosterically modifies the calcium-sensing receptors on the thick ascending limb of Henle, thereby increasing renal calcium excretion [ 17 ]. Several reports have documented hypercalciuria after the introduction of cinacalcet treatment to renal transplant patients [ 10 , 18 ], and some reports have linked hypercalciuria to nephrocalcinosis and a decline in graft function [ 13 , 19 ]. However, other studies have determined that cinacalcet has no effect on renal calcium excretion [ 11 , 12 ].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2014

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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.

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“…There are, however, at least three case reports of graft dysfunction resulting from nephrocalcinosis after the initiation of cinacalcet treatment. [29][30][31][32] CaSR is present in both parathyroid tissues and renal tubules. 33 In addition to the suppression of PTH secretion, cinacalcet can also interact directly with the CaSR expressed in renal tubules, resulting in increased calcium excretion that is independent of PTH's action on renal tubules.…”

Section: Discussionmentioning

confidence: 99%

Hyperparathyroidism in chronic kidney disease: complexities within the commonplace

et al. 2012

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-Secondary hyperparathyroidism in patients with chronic kidney disease (CKD) is common and usually caused by associated metabolic abnormalities, in particular, hypocalcaemia and hyperphosphataemia. Nevertheless, other causes of hyperparathyroidism can exist concurrently with CKD, challenging diagnostic interpretation and therapeutic intervention. We present four cases of hyperparathyroidism in patients with CKD that highlight some of these dilemmas.KEY WORDS: hyperparathyroidism, chronic kidney disease, parathyroidectomy, calcimimetic Key message:• Hyperparathyroidism in patients with chronic kidney disease (CKD) is common. While most cases are due to secondary hyperparathyroidism, other causes also need to be considered, especially when the biochemistry is incongruent.• Imaging is of limited value in distinguishing between secondary and other forms of hyperparathyroidism.• The use of calcimimetics has altered the therapeutic approach in most instances, but their long-term safety and efficacy, particularly in non-dialysis CKD patients, requires further evaluation. IntroductionSecondary hyperparathyroidism (HPT) is common in chronic kidney disease (CKD) as the result of a multitude of metabolic derangements. The prevalence of secondary hyperparathyroidism (sHPT) increases as glomerular filtration rate (GFR) reduces, from <20% in patients whose GFR is over 60 ml/min/1.73 m 2 to >50% in patients with a GFR of less than 30 ml/min/1.73 m 2 . 1 The high prevalence of sHPT in CKD, together with the attendant complexities of management, can obscure less frequent causes of hyperparathyroidism, particularly when the presenting clinical and biochemical parameters are similar. We present four cases of hyperparathyroidism and renal dysfunction that highlight the diagnostic and therapeutic dilemmas that can arise. Case 1A 66-year-old male with a past history of gastro-oesophageal reflux disease presented to his GP having lost 10 kg in weight and feeling systemically unwell. Physical examination was unremarkable. Investigations revealed an elevated serum creatinine of 193 µmol/l (this had been recorded at 100 µmol/l two years earlier). The patient was markedly hypercalcaemic (adjusted serum calcium 4.40 mmol/l), with a normal serum phosphate 0.71 mmol/l and an elevated alkaline phosphatase 235 IU/l (reference range [RR] 30-120). Parathyroid hormone concentration (PTH) was also elevated at 168 pmol/l (RR 1.0-6.5). Serum and urine electrophoresis and urine microscopy were normal, and there was no evidence of proteinuria or urinary obstruction. The patient was admitted to hospital for intravenous fluids and intravenous bisphosphonate was given to lower his serum calcium. Subsequently, a 99 Tc-Sestamibi parathyroid scan demonstrated intense uptake in the region of the left lower pole of thyroid, but there was also a focus of less intense uptake in the right lower pole of thyroid, suggesting the possibility of multiple adenomata in association with hyperparathyroidism (Fig 1). A subtotal parathyroidectomy consisting of rem...

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Renal allograft failure in a hyperparathyroid patient following initiation of a calcimimetic

Cited by 17 publications

References 22 publications

Long-Term Clinical Practice Experience with Cinacalcet for Treatment of Hypercalcemic Hyperparathyroidism after Kidney Transplantation

Long-Term Clinical Practice Experience with Cinacalcet for Treatment of Hypercalcemic Hyperparathyroidism after Kidney Transplantation

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

Hyperparathyroidism in chronic kidney disease: complexities within the commonplace

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