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Nephrol Dial Transplant (2003) 18: III81-III85
© 2003 European Renal Association-European Dialysis and Transplant Association

Original Article

Sevelamer hydrochloride, a calcium-free phosphate binder, inhibits parathyroid cell proliferation in partially nephrectomized rats

Nobuo Nagano1,, Sonoe Miyata1, Sachiko Obana1, Nami Kobayashi1, Megumi Abe1, Naoshi Fukushima2 and Michihito Wada1

1 Pharmaceutical Development Laboratories, Kirin Brewery Co., Ltd, Takasaki and 2 Fuji Gotenba Research Laboratory, Chugai Pharmaceutical Co., Ltd, Gotemba, Japan

Background. Secondary hyperparathyroidism characterized by hyperplasia of the parathyroid gland (PTG) is a consequence of chronic renal insufficiency (CRI). Dietary phosphate restriction and sevelamer hydrochloride, a calcium-free phosphate binder, suppress parathyroid hormone (PTH) secretion and PTG hyperplasia in experimental animals with CRI, independently of serum calcium and 1,25(OH)2D3 concentrations. In the present study, the effect of sevelamer on PTG cell proliferation in rats with CRI was investigated.

Methods. Seven weeks after a 5/6 nephrectomy, rats were fed a diet containing 0, 1 or 3% sevelamer for 4 weeks, and sham-operated rats were fed a normal diet. Serum calcium, phosphorus, PTH and 1,25(OH)2D3 concentrations were measured. The number of cells positive for proliferating cell nuclear antigen (PCNA) in the maximal two-dimensional PTG area was counted at the end of study.

Results. Sevelamer inhibited increases in serum phosphorus, calcium–phosphorus product and PTH concentrations without affecting serum calcium or 1,25(OH)2D3. Sevelamer also suppressed the maximal PTG area and PCNA-positive cells. There was also a strong correlation between the maximal PTG area and serum PTH concentration, and between PCNA-positive cells and the maximal PTG area, as well as between serum phosphorus concentration and PCNA-positive cells.

Conclusions. These results indicate that sevelamer treatment reduces serum phosphorus concentration and could inhibit PTG cell proliferation and prevent PTG hyperplasia.

Keywords: parathyroid cell proliferation; parathyroid gland hyperplasia; serum phosphorus; sevelamer hydrochloride

Correspondence and offprint requests to: Nobuo Nagano, PhD, Pharmaceutical Development Laboratories, Kirin Brewery Co., Ltd 3 Miyahara, Takasaki, Gunma 370-1295, Japan. Email: n-nagano{at}kirin.co.jp


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