Am J Kidney Dis. 2020 Sep 10:S0272-6386(20)30939-2. doi: 10.1053/j.ajkd.2020.07.019. Online ahead of print.
Sodium bicarbonate is the mainstay treatment of the metabolic acidosis of CKD but associated concerns center on administering sodium to patients with hypertension and sodium-retentive states. Veverimer (formerly TRC101) is a novel, non-absorbable polymer that binds H+ and Cl- in the gastrointestinal tract followed by fecal removal, thereby increasing serum [HCO3-] without administering sodium. Here, we examine the published evidence on the investigational use of veverimer, which is not FDA approved, in patients with CKD and metabolic acidosis. We highlight the achieved increase in serum [HCO3-] without coadministering sodium, effects on physical functioning, and the safety record of the drug. We also scrutinize certain unanticipated findings: a lack of dose dependency in the increase in serum [HCO3-] observed; and that despite the presumed large HCl losses in feces, veverimer induces an isochloremic rise in the serum [HCO3-] that is accompanied by a decrease in the serum anion gap. We propose likely explanations for these puzzling findings and raise questions about veverimer's mode of action and its potential interaction with colonic bacterial flora. Additional work is required to fill these knowledge gaps that could have important clinical implications.