Sevelamer: A promising but unproven drug

Suetonia C. Palmer, Jonathan C. Craig, Giovanni F.M. Strippoli

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Sevelamer hydrochloride, a synthetic phosphate binder, licensed for treatment of calcium–phosphorus abnormalities in chronic kidney disease (CKD), is one of many high-cost pharmaceuticals (lanthanum carbonate, calcimimetics, vitamin D analogues) targeted specifically at patients with the CKD-Mineral and Bone Disorder (CKD-BMD) [1]. Phosphate binders, traditionally containing calcium or aluminium, improve metabolic abnormalities in CKD by reducing absorption of dietary phosphorus. Altered mineral metabolism occurs universally in people with stage 4 and 5 CKD [2], due to impaired excretion of phosphorus, reduced activation of vitamin D and a compensatory increase in parathyroid hormone (PTH) secretion [3]. These metabolic features of CKD are associated with deleterious clinical consequences, including muscle dysfunction [4], fracture [5], cardiovascular and soft tissue calcification [6] and death. Hyperphosphataemia and treatment-related hypercalcaemia have, in large-scaled cohort studies, been powerfully, consistently and independently associated with the excess all-cause and cardiovascular mortality in CKD [7,8]. Such observational research, however, is at best hypothesis-forming, and does not elucidate the mechanisms for cause of death in these patients, and more importantly, whether reversing such metabolic disturbances prevents death. The pivotal question remains—is cardiovascular calcification on the causal chain between calcium–phosphorus–PTH imbalance and cardiovascular morbidity and mortality? Are these valid surrogate outcomes for clinical research?
Original languageEnglish
Pages (from-to)2742-2745
Number of pages4
JournalNephrology Dialysis Transplantation
Volume22
Issue number10
DOIs
Publication statusPublished - 1 Oct 2007

Keywords

  • kidney disease
  • mineral and bone disorder
  • mortality
  • phosphate binders
  • phosphorus
  • sevelamer

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