Acid loading during treatment with sevelamer hydrochloride: Mechanisms and clinical implications

Barton Brezina, Wajeh Y. Qunibi, Charles R. Nolan

Research output: Contribution to journalReview articlepeer-review

69 Scopus citations


Short-term and long-term studies indicate that patients treated with sevelamer hydrochloride have lower serum bicarbonate levels than patients treated with calcium-containing phosphate binders. This observation has previously been attributed to withdrawal of a source of base with discontinuation of calcium carbonate or calcium acetate. However, understanding of the chemistry of sevelamer hydrochloride suggests at least three potential mechanisms whereby it might induce a dietary acid load. Moreover, preliminary results from an animal model demonstrate that treatment with sevelamer hydrochloride results in a fall in urine pH, as well as an increase in urinary ammonium and calcium excretion consistent with an increase in net acid excretion. Chronic metabolic acidosis in maintenance dialysis patients is associated with major systemic effects. It is independently associated with an increased risk of death in dialysis patients. Metabolic acidosis has both catabolic and antianabolic effects that may lead to a net negative nitrogen balance and total body protein balance. Metabolic acidosis also leads to physiochemical dissolution of bone and promotes cell-mediated bone resorption due to enhanced osteoclast activity and reduced osteoblast activity. It may also exacerbate secondary hyperparathyroidism and renal osteodystrophy. Given the long-term risks of chronic metabolic acidosis in maintenance dialysis patients, Kidney/Dialysis Outcome Quality Initiative (K/DOQI) guidelines have recently recommended maintaining predialysis serum levels of CO2 above 22 mmol/L in order to improve bone histology, and to ameliorate excess protein catabolism.

Original languageEnglish (US)
Pages (from-to)S39-S45
JournalKidney International, Supplement
Issue number90
StatePublished - Sep 2004


  • Acid loading
  • Metabolic acidosis
  • Protein catabolism
  • Renal osteodystrophy
  • Sevelamer hydrochloride

ASJC Scopus subject areas

  • Nephrology


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