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

Abstract

Chronic 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-Bi2 O3 -doped (BiO)2 CO3 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.