[Effects of intermittent treatment with sevelamer hydrochloride on parathyroid hyperplasia and vascular calcification in rats with chronic kidney disease].
Phosphorus directly controls parathyroid hormone (PTH) synthesis and secretion. Serum levels of the novel phosphate-regulating hormone, fibroblast growth factor 23 (FGF23), are positively correlated with hyperphosphatemia in patients with chronic kidney disease (CKD). Rats were fed a diet containing adenine for 4 weeks to establish CKD. Animals were then offered a diet containing sevelamer hydrochloride (sevelamer) or a normal diet for alternating 2 week periods over 8 weeks. Adenine-treated rats showed marked elevations of serum phosphorus, PTH and FGF23 levels associated with parathyroid hyperplasia and aortic calcification. Serum phosphorus, PTH and FGF23 levels decreased rapidly when sevelamer treatments commenced and recovered rapidly once they were discontinued. However, intermittent treatment with sevelamer successfully inhibited parathyroid hyperplasia and aortic calcification. In conclusion, phosphate-binder treatment can effectively inhibit the elevation of serum FGF23 levels, as well as PTH levels, under conditions of CKD. Setting up a period of reduced serum phosphorus levels, even if it is intermittent, is worthwhile for the inhibition of the development of parathyroid hyperplasia and aortic calcification.
Nagano
Nobuo
N
Medical Affairs Section and Pharmaceutical Development Laboratories, Pharmaceutical Division, Kirin Brewery Company, Limited.
Miyata
Sonoe
S
Abe
Megumi
M
Wakita
Sachiko
S
Kobayashi
Nami
N
Wada
Michihito
M
D000225:Adenine; D000818:Animals; D001018:Aortic Diseases / Q000188:drug therapy* / Q000209:etiology; D002114:Calcinosis / Q000188:drug therapy* / Q000209:etiology; D002118:Calcium / Q000097:blood; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D005346:Fibroblast Growth Factors / Q000097:blood*; D006962:Hyperparathyroidism, Secondary / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D006965:Hyperplasia / Q000188:drug therapy / Q000209:etiology; D007676:Kidney Failure, Chronic / Q000097:blood / Q000139:chemically induced / Q000150:complications*; D008297:Male; D010280:Parathyroid Glands / Q000473:pathology*; D010281:Parathyroid Hormone / Q000097:blood*; D010758:Phosphorus / Q000097:blood; D011073:Polyamines / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000069603:Sevelamer
C505605:Fgf23 protein, rat; D010281:Parathyroid Hormone; D011073:Polyamines; D010758:Phosphorus; D005346:Fibroblast Growth Factors; D000069603:Sevelamer; D000225:Adenine; D002118:Calcium