Sevelamer hydrochloride (Renagel), a non-calcaemic phosphate binder, arrests parathyroid gland hyperplasia in rats with progressive chronic renal insufficiency.
BACKGROUND
It has been demonstrated that dietary phosphate restriction suppresses parathyroid hormone (PTH) secretion and parathyroid cell proliferation in experimental animals with chronic renal insufficiency (CRI) independently of serum calcium and 1,25(OH)(2)D3 levels. This study was conducted to examine whether sevelamer hydrochloride (Renagel); hereafter referred to as sevelamer), a non-calcaemic phosphate binder could inhibit the parathyroid gland (PTG) hyperplasia in rats with progressive CRI.


METHODS
Male Sprague-Dawley rats were injected twice with low doses of adriamycin (ADR). Two weeks after the last injection of ADR, rats were fed a diet containing 1 or 3% sevelamer for 84 days. Time course changes of serum levels of calcium, phosphorus, and PTH were measured. At the end of study, serum 1,25(OH)(2)D3 levels were measured and the maximal two-dimension area of the PTG in paraffin section was calculated using an imaging analyser.


RESULTS
Dietary sevelamer treatment inhibited the elevations of serum phosphorus, calciumxphosphorus product, and PTH levels that occurred as the study progressed. Sevelamer also suppressed maximal PTG area and there existed positive strong correlation between maximal PTG area and serum PTH levels at the end of the study. Serum phosphorus levels positively correlated well with serum PTH levels and maximal PTG area. In contrast, serum calcium or 1,25(OH)(2)D3 levels did not show any correlation with serum PTH levels and maximal PTG area.


CONCLUSIONS
Sevelamer treatment arrested hyperphosphataemia and PTG hyperplasia accompanied by the elevation of serum PTH levels. The correlation analysis suggests that reduced serum phosphorus levels contributed to the suppression of PTG hyperplasia and resulted in the reduction of PTH levels in this animal model after the sevelamer treatment. The management of phosphorus control started from early stage of CRI could prevent PTG hyperplasia and facilitate later management of secondary hyperparathyroidism.
Nagano
N
N
Pharmaceutical Development Laboratories, Kirin Brewery Co., Ltd, 3 Miyahara-cho, Takasaki-shi, Gunma 370-1295, Japan.
Miyata
S
S
Obana
S
S
Ozai
M
M
Kobayashi
N
N
Fukushima
N
N
Burke
S K
SK
Wada
M
M
D000818:Animals; D001769:Blood / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002118:Calcium / Q000097:blood; D018450:Disease Progression; D004435:Eating / Q000187:drug effects; D004852:Epoxy Compounds / Q000378:metabolism / Q000627:therapeutic use*; D006965:Hyperplasia; D007676:Kidney Failure, Chronic / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D010280:Parathyroid Glands / Q000187:drug effects* / Q000473:pathology*; D010281:Parathyroid Hormone / Q000097:blood; D010710:Phosphates / Q000378:metabolism; D010758:Phosphorus / Q000097:blood; D011073:Polyamines; D011095:Polyethylenes / Q000378:metabolism / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000069603:Sevelamer; D014556:Urine / Q000737:chemistry
D004852:Epoxy Compounds; D010281:Parathyroid Hormone; D010710:Phosphates; D011073:Polyamines; D011095:Polyethylenes; D010758:Phosphorus; D000069603:Sevelamer; D002118:Calcium