Chapter 52: Acid–Base Disorders

Content Update

September 29, 2019

Veverimer: A Promising Investigational Agent for Long-Term Treatment of Metabolic Acidosis in Chronic Kidney Disease: Veverimer is an oral non-absorbed acid binder that sequesters hydrochloric acid in the gastrointestinal tract, preventing its absorption and thereby raising serum bicarbonate concentrations. In a randomized one-year clinical trial in CKD patients with metabolic acidosis, patients taking veverimer achieved greater increases in serum bicarbonate and were more likely to achieve increases ≥4 mmol/L and/or into the reference range than patients taking placebo. Overall, veverimer was well tolerated, with adverse event rates similar to placebo. Veverimer effectively raises serum bicarbonate levels in stage IIIb–IV CKD patients via a sodium-independent mechanism. If approved by the U.S. FDA, it may provide a new option for patients with severe CKD and sodium- or volume-dependent comorbidities who may otherwise require renal replacement therapy for acidosis control.

KEY CONCEPTS

• The kidney plays a central role in the regulation of acid–base homeostasis through the excretion or reabsorption of filtered bicarbonate (HCO₃^-), the excretion of metabolic fixed acids, and the generation of new HCO₃^-.

• Arterial blood gases (ABGs), along with serum electrolytes, physical findings, medical and medication history, and the clinical condition of the patient, are the primary tools to determine the cause of an acid–base disorder and to design and monitor a course of therapy.

• Each acid-base disturbance has a compensatory response that attempts to correct the HCO₃^--to-PaCO₂ ratio toward normal and mitigate the change in pH. The respiratory compensatory response to metabolic disturbances is initiated rapidly whereas the metabolic compensatory response to respiratory disturbances occurs more slowly.

• Metabolic acidosis and metabolic alkalosis are generated by a primary change in the serum bicarbonate concentration. In metabolic acidosis, bicarbonate is lost or a nonvolatile acid is gained, whereas metabolic alkalosis is characterized by a gain in bicarbonate or a loss of nonvolatile acid.

• Renal tubular acidosis (RTA) refers to a group of disorders characterized by impaired tubular renal acid handling despite normal or near-normal glomerular filtration rates. These patients often present with hyperchloremic metabolic acidosis.

• Although respiratory compensation for a primary metabolic acidosis begins rapidly (within 15-30 minutes) it does not reach a steady state for 12 to 24 hours after the onset of metabolic acidosis.

• Primary therapy of most acid–base disorders must include treatment or removal of the underlying cause, not just correction of the pH and electrolyte disturbances.

• Potassium supplementation is always necessary for patients with chronic metabolic acidosis, as the bicarbonaturia resulting from alkali therapy increases renal potassium wasting.

• Effective treatment of the underlying cause of some organic acidoses (eg, ketoacidosis) can result in bicarbonate regenera­tion within hours thus mitigating the need for alkali therapy.

• Loss of gastric acid from ...