A Counterion‐Free Strategy for Chronic Metabolic Acidosis Based on an Orally Administered Gut‐Restricted Inorganic Adsorbent

Abstract

AbstractChronic metabolic acidosis, arising as a complication of chronic kidney disease (CKD), not only reduces patients’ quality of life but also aggravates renal impairment. The only available therapeutic modality, involving intravenous infusion of NaHCO3, engenders undesirable sodium retention, thereby increasing hemodynamic load and seriously exacerbating the primary disease. This deleterious cascade extends to the development of cardiovascular diseases. Herein, an orally administered, gut‐restricted inorganic adsorbent that can effectively alleviate chronic metabolic acidosis without causing any electrolytic derangement or superfluous cardiovascular strain is developed. The genesis of ABC‐350 entails the engineering of bismuth subcarbonate via annealing, thereby yielding a partially β‐Bi2O3‐doped (BiO)2CO3 biphasic crystalline structure framework enriched with atomic vacancies. ABC‐350 can selectively remove chloride ions and protons from the gastrointestinal tract, mimicking the physiological response to gastric acid removal and resulting in increased serum bicarbonate. Owing to its gut‐restricted nature, ABC‐350 exhibits commendable biosafety, averting undue systemic exposure. In two rat models of metabolic acidosis, ABC‐350 emerges not only as a potent mitigator of acidosis but also effects discernible amelioration concerning proximal tubular morphology, interstitial fibrosis, and the incendiary cascades incited by metabolic acidosis. ABC‐350, as the translationally relevant material, provides a promising strategy for the treatment of metabolic acidosis.