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Combination therapy with sevelamer hydrochloride and calcium carbonate in Japanese patients with long-term hemodialysis: alternative approach for optimal mineral management.

Abstract
Calcium (Ca) overload by Ca-containing phosphorus (P) binder has been suggested to be implicated in the pathogenesis of soft tissue and vascular calcification, which contribute to increased morbidity and mortality of cardiovascular disease in patients undergoing dialysis. Recently, a noncalcium P binder, sevelamer hydrochloride (sevelamer), has become available in Japan. However, Japanese patients undergoing dialysis might be less tolerant of sevelamer treatment, and it is likely to cause hypocalcemia because their dietary Ca intake is less than that in European and American patients. We evaluated the effects of combination therapy with sevelamer and calcium carbonate (CC) on mineral metabolism in Japanese hemodialysis patients, as an alternative form of P management. A total of 210 hemodialysis patients were enrolled, and were given a small dose of sevelamer (0.75-1.5 g/day) on CC treatment. Sevelamer dose was gradually increased, while CC decreased during 24 weeks. Five patients discontinued sevelamer treatment because of severe constipation, anorexia, and parathyroidectomy for severe secondary hyperparathyroidism. After 24 weeks, the dose of sevelamer was significantly increased to 3.29 g/day (initial dose: 1.47 g/day), while CC was decreased by 54%. Adjusted serum Ca significantly decreased (9.63 +/- 0.57-9.45 +/- 0.67 mg/dL; P = 0.0012), although serum P increased (5.89 +/- 1.32-6.25 +/- 1.32 mg/dL; P = 0.017). Serum intact PTH (iPTH) significantly increased in patients with a low or normal iPTH level (< or =300 pg/mL), while it did not change in patients with secondary hyperparathyroidism (>300 pg/mL). The results suggest that the therapeutic regimen is more tolerant and reduces Ca load in Japanese hemodialysis patients while avoiding hypocalcemia. In addition, the mitigated Ca overload could improve PTH hyposecretion in patients with adynamic bone disease, which is associated with soft tissue calcification and higher mortality in uremia.
AuthorsHiroaki Ogata, Fumihiko Koiwa, Kanji Shishido, Eriko Kinugasa
JournalTherapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy (Ther Apher Dial) Vol. 9 Issue 1 Pg. 11-5 (Feb 2005) ISSN: 1744-9979 [Print] Australia
PMID15828900 (Publication Type: Journal Article)
Chemical References
  • Antacids
  • Calcium, Dietary
  • Epoxy Compounds
  • Parathyroid Hormone
  • Polyamines
  • Polyethylenes
  • Phosphorus
  • Sevelamer
  • Calcium Carbonate
  • Calcium
Topics
  • Antacids (therapeutic use)
  • Bone Density
  • Bone and Bones (metabolism)
  • Calcium (blood)
  • Calcium Carbonate (therapeutic use)
  • Calcium, Dietary (administration & dosage)
  • Chronic Kidney Disease-Mineral and Bone Disorder (etiology)
  • Drug Therapy, Combination
  • Epoxy Compounds (therapeutic use)
  • Humans
  • Hyperparathyroidism, Secondary (etiology)
  • Japan
  • Kidney Failure, Chronic (complications, therapy)
  • Parathyroid Hormone (blood)
  • Phosphorus (blood)
  • Polyamines
  • Polyethylenes (therapeutic use)
  • Renal Dialysis
  • Sevelamer
  • Time Factors

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