NDT Advance Access originally published online on August 22, 2005
Nephrology Dialysis Transplantation 2005 20(12):2865; doi:10.1093/ndt/gfi110
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Therapeutic failure of cinacalcet in a renal transplant patient presenting hyperparathyroidism with severe hypercalcaemia
Email: henri.boulanger{at}sls.ap-hop-paris.frSir,
In our experience, 
10% of renal allograft recipients develop sustained hyperparathyroidism and hypercalcaemia during the first year following renal transplantation. Persistent hypercalcaemia usually requires parathyroidectomy, which represents the only definitive treatment currently available. Cinacalcet, a calcimimetic drug, represents from now on an alternative therapy to avoid surgery. Recent studies have reported successful control of hypercalcaemia by this drug in this situation [1–3].
We report the case of a 25-year-old man, on peritoneal dialysis since 2003, who received a renal graft in November 2004 and developed after transplantation sustained hypercalcaemia at 3.35 mmol/l (normal range, 2.2–2.6) with a high level of ionized calcium at 1.88 mmol/l (normal range, 1.14–1.31) and an inappropriate plasmatic secretion of parathyroid hormone (PTH) at 607 pg/ml (normal range, 10–55). The glomerular filtration rate, assessed by creatinine clearance, was 73 ml/min/1.73 m. Treatment with cinacalcet was initiated, at 4 months post transplantation, in an attempt to avoid parathyroidectomy. Despite 2 months of treatment with increasing doses of oral cinacalcet (up to 120 mg once daily), hypercalcaemia at 3.09 mmol/l (ionized calcium, 1.61 mmol/l) persisted with seric PTH concentration of 314 pg/ml. Interestingly hypercalciuria, which was not present in the early post transplantation period (urinary calcium, 4.6 mmol/24 h), appeared upon cinacalcet treatment with value at 16 mmol/24 h. Because of the persistent threatening high level of serum calcium (value at 3.36 mmol/l) associated with hypercalciuria, a sub total parathyroidectomy was finally performed.
The reasons for the resistance to cinacalcet need to be elucidated. Non observance of treatment can be excluded. A possible explanation could be a defect of sensitivity to extra cellular calcium or to the calcimimetic drug by the parathyroid cells. This observation also suggests, though not previously observed in studies, that cinacalcet could be responsible for a urinary calcium excretion increase by a direct effect on the calcium sensor located in the thick ascending limb of Henle [4,5]. Indeed, activating mutation of calcium sensor receptor could provide mechanism for the developments of Bartter's syndrome, which is characterized by an increase in urinary calcium [6,7].
In conclusion, this case demonstrates a therapeutic failure of cinacalcet in a renal transplant patient presenting hypercalcaemia with inappropriate secretion of PTH. Furthermore increase of urinary calcium during cinacalcet treatment must be emphasized and needs to be clarified because it has not been observed in renal transplant recipients who respond successfully to cinacalcet [2,4]. Therefore, further studies, with larger numbers of patients, are required to better define which kind of patient could have resistance and to unravel the real effect of cinacalcet on urinary calcium tubular excretion.
Conflict of interest statement. None declared.
1 Department of Nephrology and Transplantation Saint-Louis Hospital2 Department of Renal Physiology Tenon Hospital3 Department of General Surgery Saint-Louis Hospital Paris France
References
- Lindberg JS, Culleton B, Wong G et al. Cinacalcet HCl, an oral calcimimetic agent for the treatment of secondary hyperparathyroidism in hemodialysis and peritoneal dialysis: randomized, double-blind, multicenter study. J Am Soc Nephrol 2005; 16: 800–807
[Abstract/Free Full Text] - Serra AL, Schwartz AA, Wick FH, Marti HP, Wuthrich RP. Successful treatment of hypercalcemia with cinacalcet in renal transplant recipients with persistent hyperparathyroidism. Nephrol Dial Transplant 2005; 20: 1315–1319
[Abstract/Free Full Text] - Kruse AE, Eisenberger U, Frey FJ, Mohaupt MG. The calcimimetic cinacalcet normalizes serum calcium in renal transplant patients with persistent hyperparathyroidism. Nephrol Dial Transplant 2005; 20: 1311–1314
[Abstract/Free Full Text] - Shoback DM, Bilezikian JP, Turner SA, McCary LC, Guo MD, Peacock M. The calcimimetic cinacalcet normalizes serum calcium in subjects with primary hyperparathyroidism. J Clin Endocrinol Metab 2003; 88: 5644–5649
[Abstract/Free Full Text] - Chattopadhyay N, Mithal A, Brown EM. The calcium-sensing receptor: a window into the physiology and pathophysiology of mineral ion metabolism. Endocrine Rev 1996; 17: 289–307[Abstract]
- Watanabe S, Fukumoto S, Chang H et al. Association between activating mutations of calcium sensing receptor and Bartter's syndrome. Lancet 2002; 360: 692–694[CrossRef][ISI][Medline]
- Hebert SC. Bartter syndrome. Curr Opin Nephrol Hypertens 2003; 12: 527–532[ISI][Medline]
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