Sodium zirconium cyclosilicate and metabolic acidosis: Potential mechanisms and clinical consequences - 13/01/23
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 (NH4+) 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+. 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.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Highlights |
• | Metabolic acidosis is common, underdiagnosed and undertreated in patients with CKD. |
• | However, metabolic acidosis is associates with adverse outcomes. |
• | Sodium zirconium cyclosilicate (SZC) is in clinical use for hyperkalemia. |
• | SZC also increased serum bicarbonate and decreased serum urea. |
• | A research roadmap is proposed to address the clinical significance of this effect. |
Keywords : Chronic kidney disease, Veverimer, Sodium bicarbonate, Hyperkalemia, Carbamylation, Urea, Research roadmap
Plan
Vol 158
Article 114197- février 2023 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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