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Editorial
. 2020 Oct;8(20):1331.
doi: 10.21037/atm-20-2827.

Veverimer: an advance in base therapy for metabolic acidosis

Clayton Brady  1 , Elie R Chemaly  2 , James W Lohr  2 , Mark D Parker  1
Affiliations
Editorial

Veverimer: an advance in base therapy for metabolic acidosis

Clayton Brady et al. Ann Transl Med. 2020 Oct.
No abstract available

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Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-2827). The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
A network of pathologies associated with CKD-MAc. The effects of CKD-MAc are multifaceted and incompletely understood. Acid retention can trigger inflammatory mechanisms (e.g., complement activation and cytokine release), which leads to kidney interstitial fibrosis and worsening of CKD. Chronic low pH decreases bone mineralization and increases muscle protein metabolism leading to increased fragility in patients. Activation of hormonal mechanisms (e.g., endothelin and angiotensin II release) can also damage the kidney, as well as cause fluid retention and atherosclerotic plaque development that can lead to development of cardiovascular disease. Evidence that high (HCO3−) may also be associated with cardiovascular disease adds to the complexity of potential treatment guidelines. Overall, worsening CKD to the point of needing dialysis and the progression of co-morbid conditions such as fragility and cardiovascular disease, together decrease independence and contribute directly to mortality. See reference (5) for a more thorough review.
Figure 2
Figure 2
The mechanism of action of veverimer versus sodium bicarbonate in the treatment of MAc. (A) Parietal cells secrete H+ across their apical membranes using a H+/K+-ATPase. Intracellular H+ are replaced by the action of carbonic anhydrase II (CAII), which also generates HCO3− that must be absorbed into the blood to maintain parietal cell pH. This is achieved by the exchange of intracellular HCO3− for interstitial Cl−, a process mediated by the anion exchange protein AE2. (B) HCl in the stomach lumen may be neutralized by orally administered NaHCO3 with the production of unwanted NaCl and CO2. Veverimer sequesters HCl in the stomach lumen, removing H+ without generating these byproducts. The effectiveness of veverimer is such that it temporarily causes gastric pH to rise between 1.5–3.0 units (7). The replacement of gastric acid that was neutralized by these treatments results in the enhanced production of HCO3− by parietal cells, mimicking a postprandial alkaline tide.
See this image and copyright information in PMC

Comment on

References

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