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

Barton Brezina, Wajeh Y Qunibi, Charles R. Nolan

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

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)
JournalKidney International, Supplement
Volume66
Issue number90
StatePublished - Sep 2004

Fingerprint

Acidosis
Dialysis
Acids
calcium acetate
Maintenance
Chronic Kidney Disease-Mineral and Bone Disorder
Therapeutics
Bone and Bones
Secondary Hyperparathyroidism
Calcium Carbonate
Osteoclasts
Bone Resorption
Bicarbonates
Serum
Osteoblasts
Ammonium Compounds
Histology
Proteins
Nitrogen
Animal Models

Keywords

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

ASJC Scopus subject areas

  • Nephrology

Cite this

Acid loading during treatment with sevelamer hydrochloride : Mechanisms and clinical implications. / Brezina, Barton; Qunibi, Wajeh Y; Nolan, Charles R.

In: Kidney International, Supplement, Vol. 66, No. 90, 09.2004.

Research output: Contribution to journalArticle

Brezina, Barton ; Qunibi, Wajeh Y ; Nolan, Charles R. / Acid loading during treatment with sevelamer hydrochloride : Mechanisms and clinical implications. In: Kidney International, Supplement. 2004 ; Vol. 66, No. 90.
@article{bc46e0f3707e4e6b99994282b45de539,
title = "Acid loading during treatment with sevelamer hydrochloride: Mechanisms and clinical implications",
abstract = "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.",
keywords = "Acid loading, Metabolic acidosis, Protein catabolism, Renal osteodystrophy, Sevelamer hydrochloride",
author = "Barton Brezina and Qunibi, {Wajeh Y} and Nolan, {Charles R.}",
year = "2004",
month = "9",
language = "English (US)",
volume = "66",
journal = "Kidney International, Supplement",
issn = "0098-6577",
publisher = "Wiley-Blackwell",
number = "90",

}

TY - JOUR

T1 - Acid loading during treatment with sevelamer hydrochloride

T2 - Mechanisms and clinical implications

AU - Brezina, Barton

AU - Qunibi, Wajeh Y

AU - Nolan, Charles R.

PY - 2004/9

Y1 - 2004/9

N2 - 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.

AB - 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.

KW - Acid loading

KW - Metabolic acidosis

KW - Protein catabolism

KW - Renal osteodystrophy

KW - Sevelamer hydrochloride

UR - http://www.scopus.com/inward/record.url?scp=4344685263&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=4344685263&partnerID=8YFLogxK

M3 - Article

C2 - 15296506

AN - SCOPUS:4344685263

VL - 66

JO - Kidney International, Supplement

JF - Kidney International, Supplement

SN - 0098-6577

IS - 90

ER -