Sevelamer hydrochloride prevents ectopic calcification and renal osteodystrophy in chronic renal failure rats.
BACKGROUND
Hyperphosphatemia is associated with severe complications, including ectopic calcification of soft tissues, secondary hyperparathyroidism, and renal osteodystrophy (ROD). Sevelamer hydrochloride is a nonabsorbed calcium- and metal-free phosphate binder that lowers serum phosphorus levels in hemodialysis patients. This study examined the efficacy of sevelamer in preventing ectopic calcification of soft tissues and ROD in adenine-induced renal failure rats.


METHODS
Male, 12-week-old Wistar-Jcl rats were freely fed an adenine diet (0.75 g adenine in 100 g normal diet) for four weeks. After three weeks of the adenine diet, when serum phosphorus levels had significantly increased, the rats were freely fed a normal diet that contained 1% or 2% of sevelamer for another five weeks. Time course changes of serum levels of phosphorus, calcium, and parathyroid hormone (PTH) were measured. At the end of the study, calcium and phosphorus levels in the heart and aorta were measured, and the calcification of kidney, heart, aorta, and stomach were histopathologically examined. The severity of ROD was evaluated by a histopathologic and morphometric analysis of the femurs.


RESULTS
Compared with the adenine controls (N = 10), the sevelamer-treated (1%, N = 6; and 2%, N = 10) groups of adenine-induced renal failure rats had reduced serum phosphorus, serum calcium x phosphorus product, and serum PTH levels. Moreover, in the treatment groups, sevelamer suppressed calcification of the aorta media, and also the osteoid volume, fibrosis volume, and porosity ratio of femurs.


CONCLUSIONS
These results suggest that sevelamer treatment might contribute to the suppression of ectopic calcification and ROD.
Katsumata
Kyoko
K
Fuji Gotemba Research Laboratory, Chugai Pharmaceutical Co., Ltd., Shizuoka, Japan.
Kusano
Kenichiro
K
Hirata
Michinori
M
Tsunemi
Kunihiko
K
Nagano
Nobuo
N
Burke
Steven K
SK
Fukushima
Naoshi
N
D000818:Animals; D002114:Calcinosis / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D002118:Calcium / Q000097:blood; D012080:Chronic Kidney Disease-Mineral and Bone Disorder / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D003404:Creatinine / Q000097:blood; D004852:Epoxy Compounds / Q000494:pharmacology*; D007676:Kidney Failure, Chronic / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D008297:Male; D010758:Phosphorus / Q000097:blood; D011073:Polyamines; D011095:Polyethylenes / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D000069603:Sevelamer
D004852:Epoxy Compounds; D011073:Polyamines; D011095:Polyethylenes; D010758:Phosphorus; D000069603:Sevelamer; D003404:Creatinine; D002118:Calcium