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Sodium zirconium cyclosilicate and metabolic acidosis: Potential mechanisms and clinical consequences.
- Source :
-
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2023 Feb; Vol. 158, pp. 114197. Date of Electronic Publication: 2023 Jan 04. - Publication Year :
- 2023
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Abstract
- Metabolic acidosis is frequent in chronic kidney disease (CKD) and is associated with accelerated progression of CKD, hypercatabolism, bone disease, hyperkalemia, and mortality. Clinical guidelines recommend a target serum bicarbonate ≥ 22 mmol/L, but metabolic acidosis frequently remains undiagnosed and untreated. Sodium zirconium cyclosilicate (SZC) binds potassium in the gut and is approved to treat hyperkalemia. In clinical trials with a primary endpoint of serum potassium, SZC increased serum bicarbonate, thus treating CKD-associated metabolic acidosis. The increase in serum bicarbonate was larger in patients with more severe pre-existent metabolic acidosis, was associated to decreased serum urea and was maintained for over a year of SZC therapy. SZC also decreased serum urea and increased serum bicarbonate after switching from a potassium-binding resin in normokalemic individuals. Mechanistically, these findings are consistent with SZC binding the ammonium ion (NH <subscript>4</subscript> <superscript>+</superscript> ) generated from urea by gut microbial urease, preventing its absorption and, thus, preventing the liver regeneration of urea and promoting the fecal excretion of H <superscript>+</superscript> . This mechanism of action may potentially result in benefits dependent on corrected metabolic acidosis (e.g., improved well-being, decreased catabolism, improved CKD mineral bone disorder, better control of serum phosphate, slower progression of CKD) and dependent on lower urea levels, such as decreased protein carbamylation. A roadmap is provided to guide research into the mechanisms and clinical consequences of the impact of SZC on serum bicarbonate and urate.<br />Competing Interests: Conflict of interest statement AO has received grants from Sanofi and consultancy or speaker fees or travel support from Advicciene, Astellas, Astrazeneca, Amicus, Amgen, Boehringer-Ingelheim, Fresenius Medical Care, GSK, Bayer, Sanofi-Genzyme, Lilly, Menarini, Mundipharma, Kyowa Kirin, Alexion, Freeline, Idorsia, Chiesi, Otsuka, Novo-Nordisk, Sysmex and Vifor Fresenius Medical Care Renal Pharma and is Director of the Catedra Mundipharma-UAM of diabetic kidney disease and the Catedra Astrazeneca-UAM of chronic kidney disease and electrolytes.<br /> (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
Details
- Language :
- English
- ISSN :
- 1950-6007
- Volume :
- 158
- Database :
- MEDLINE
- Journal :
- Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
- Publication Type :
- Academic Journal
- Accession number :
- 36916426
- Full Text :
- https://doi.org/10.1016/j.biopha.2022.114197