Sevelamer hydrochloride, a calcium-free phosphate binder, inhibits parathyroid cell proliferation in partially nephrectomized rats.
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)(2)D(3) 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)(2)D(3) 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)(2)D(3). 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.
Nagano
Nobuo
N
Pharmaceutical Development Laboratories, Kirin Brewery Co, Ltd, Takasaki, Japan. n-nagano@kirin.co.jp
Miyata
Sonoe
S
Obana
Sachiko
S
Kobayashi
Nami
N
Abe
Megumi
M
Fukushima
Naoshi
N
Wada
Michihito
M
D000818:Animals; D002117:Calcitriol / Q000097:blood; D002118:Calcium / Q000097:blood; D002455:Cell Division / Q000187:drug effects; D004852:Epoxy Compounds / Q000494:pharmacology*; D008297:Male; D009392:Nephrectomy / Q000379:methods; D009929:Organ Size / Q000187:drug effects; D009994:Osmolar Concentration; D010280:Parathyroid Glands / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D010281:Parathyroid Hormone / Q000097:blood; D010758:Phosphorus / Q000097:blood; D011073:Polyamines; D011095:Polyethylenes / Q000494:pharmacology*; D011184:Postoperative Period; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000069603:Sevelamer
D004852:Epoxy Compounds; D010281:Parathyroid Hormone; D011073:Polyamines; D011095:Polyethylenes; D018809:Proliferating Cell Nuclear Antigen; D010758:Phosphorus; D000069603:Sevelamer; D002117:Calcitriol; D002118:Calcium