NDT Advance Access originally published online on October 6, 2007
Nephrology Dialysis Transplantation 2008 23(1):407-408; doi:10.1093/ndt/gfm623
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Can calcimimetics inhibit nodular hyperplasia of parathyroid glands?
Email: fukagawa{at}med.kobe-u.ac.jpSir,
In a recent editorial review, Drueke and associates [1] summarized the pre-clinical data on the pathogenesis of parathyroid hyperplasia in chronic kidney disease (CKD) and its possible prevention and treatment by calcimimetics. Although intensively discussed, the authors have left an important clinical issue unsolved, i.e. whether calcimimetics can effectively control parathyroid hyperfunction in patients with nodular hyperplasia, the advanced type of parathyroid hyperplasia. As they noted, nodular hyperplasia cannot be replicated in model animals of CKD even with the most severe hyperparathyroidism.
It has been well recognized that cells in nodular hyperplasia have reduced numbers of vitamin D receptor (VDR) and calcium-sensing receptor (CaSR), thus usually refractory to medical therapies [2]. Development of nodular hyperplasia has been most efficiently diagnosed by the size of the enlarged glands evaluated by ultrasonography, and 0.5 cm3 has been approximately considered to be the critical size. Even in a recent clinical study with maxacalcitol, an active vitamin D analogue for intravenous administration, it was unable to control PTH secretion in patients with enlarged glands of this size [3].
With respect to this issue, recent observations in patients with hypercalcaemia due to persistent hyperparathyroidism after kidney transplantation seem to be promising 4,*5. Cinacalcet was effective in suppressing PTH levels at least in a part of such patients, in whom parathyroidectomy was usually indicated.
As we have recently revealed [6], the numbers of VDR and CaSR in nodular hyperplasia recipients remained reduced even after successful kidney transplantation, in sharp contrast to the putative improvement in diffuse hyperplasia. Since series of evidences support the association of persistent hyperparathyroidism after kidney transplantation with nodular hyperplasia, these findings suggest a possible control of nodular hyperplasia by calcimimetics.
Accordingly, it is crucial to examine whether caicimicetics alone or in combination with active vitamin D sterols can control hyperparathyroidism in CKD patients with nodular hyperplasia, by well-designed prospective clinical studies. We are planning to perform such studies when cinacalcet becomes available in Japan in the near future.
Conflict of interest statement. Msafumi Fukugawa is a member of advisory commitee for clinical study of cinacalcet in Japan.
1Division of Nephrology &
Kidney Center, Kobe University
School of Medicine, Kobe
2Department of Medicine and Clinical Sciences
Kyushu University, Fukuoka, Japan
References
- Drueke T, Martin D, Rodriguez M. Can calcmimetics inhibit parathyroid hyperplasia? Evidence from preclinical studies. Nephrol Dial Transplant (2007) [Epub ahead of print], doi:10.1093/ndt/gfm.
- Fukagawa M, Nakanishi S, Kazama JJ. Basic and clinical aspects of parathyroid hyperplasia in chronic kidney disease. Kidney Int (2006) 70(Suppl 102):S3–S7.
- Tominaga Y, Inaguma D, Matsuoka S, et al. PTG study group. Is the volume of the parathyroid gland a predictor of maxacalcitol response in advanced secondary hyperparathyroidism? Ther Apher Dial (2006) 10:198–204.[CrossRef][Web of Science][Medline]
- Serra AL, Schwarz 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] - Srinivas TR, Schold JD, Womer KL, et al. Improvement in hypercalcemia with cinacalcet after kidney transplantation. Clin J Am Soc Nephrol (2006) 1:323–326.
[Abstract/Free Full Text] - Taniguchi M, Tokumoto M, Matuo D, et al. Persistent hyperparathyroidism in renal allograft recipients: vitamin D receptor, calcium-sensing receptor, and apoptosis. Kidney Int (2006) 70:363–370.[CrossRef][Web of Science][Medline]
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  M. Tanaka, S. Nakanishi, H. Komaba, K. Itoh, K. Matsushita, and M. Fukagawa Association between long-term efficacy of cinacalcet and parathyroid gland volume in haemodialysis patients with secondary hyperparathyroidism NDT Plus, August 1, 2008; 1(suppl_3): iii49 - iii53. [Abstract] [Full Text] [PDF]
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