title: Long-term treatment with lanthanum carbonate reduces mineral and bone abnormalities in rats with chronic renal failure.
abstract: BACKGROUND
  Lanthanum carbonate (FOSRENOL(®), Shire Pharmaceuticals) is an effective non-calcium, non-resin phosphate binder for the treatment of hyperphosphataemia in patients with chronic kidney disease (CKD). In this study, we used a rat model of chronic renal failure (CRF) to examine the long-term effects of controlling serum phosphorus with lanthanum carbonate treatment on the biochemical and bone abnormalities associated with CKD-mineral and bone disorder (CKD-MBD).
  
  
  METHODS
  Rats were fed a normal diet (normal renal function, NRF), or a diet containing 0.75% adenine for 3 weeks to induce CRF. NRF rats continued to receive normal diet plus vehicle or normal diet supplemented with 2% (w/w) lanthanum carbonate for 22 weeks. CRF rats received a diet containing 0.1% adenine, with or without 2% (w/w) lanthanum carbonate. Blood and urine biochemistry were assessed, and bone histomorphometry was performed at study completion.
  
  
  RESULTS
  Treatment with 0.75% adenine induced severe CRF, as demonstrated by elevated serum creatinine. Hyperphosphataemia, hypocalcaemia, elevated calcium × phosphorus product and secondary hyperparathyroidism were evident in CRF + vehicle animals. Treatment with lanthanum carbonate reduced hyperphosphataemia and secondary hyperparathyroidism in CRF animals (P < 0.05), and had little effect in NRF animals. Bone histomorphometry revealed a severe form of bone disease with fibrosis in CRF + vehicle animals; lanthanum carbonate treatment reduced the severity of the bone abnormalities observed, particularly woven bone formation and fibrosis.
  
  
  CONCLUSIONS
  Long-term treatment with lanthanum carbonate reduced the biochemical and bone abnormalities of CKD-MBD in a rat model of CRF.
authors.affiliation: Shire Pharmaceuticals, Basingstoke, UK. sdamment@shire.com
authors.forename: Stephen
authors.initials: S
authors.lastname: Damment
authors.forename: Roger
authors.initials: R
authors.lastname: Secker
authors.forename: Victor
authors.initials: V
authors.lastname: Shen
authors.forename: Victor
authors.initials: V
authors.lastname: Lorenzo
authors.forename: Mariano
authors.initials: M
authors.lastname: Rodriguez
mesh_terms: D000818:Animals; D001847:Bone Diseases / Q000517:prevention & control*; D002113:Calcification, Physiologic / Q000187:drug effects*; D002118:Calcium / Q000097:blood; D007676:Kidney Failure, Chronic / Q000097:blood / Q000517:prevention & control*; D007811:Lanthanum / Q000627:therapeutic use*; D008297:Male; D008903:Minerals / Q000378:metabolism*; D010758:Phosphorus / Q000097:blood; D051381:Rats; D017208:Rats, Wistar
chemical_list: D008903:Minerals; D010758:Phosphorus; C119467:lanthanum carbonate; D007811:Lanthanum; D002118:Calcium