ADVERSE EFFECTS

The major adverse effects of CAIs include:

• Metabolic acidosis
  
• Nephrolithiasis, owing to urine alkalinization
  
• Increased serum ammonia concentration, secondary to impaired renal excretion, which may cause encephalopathy in patients with cirrhosis
  
• Bone marrow suppression
  
• Skin toxicity
  
• Confusion, drowsiness, and paresthesia, secondary to central nervous system effects

CAIs increase K⁺ excretion in several ways. First, the increased Na⁺ load that reaches the distal nephron creates a negative intraluminal charge as it is reabsorbed, which promotes K⁺ secretion through apical renal outer medullary potassium (ROM-K) channels. Second, the increased HCO₃⁻ load that reaches the distal nephron also generates a negative intraluminal charge, which promotes K⁺ secretion for the same reasons. Finally, the increased urine flow through the distal nephron promotes K⁺ secretion through flow-sensitive maxi-K channels. Such kaliuresis, however, rarely leads to hypokalemia because metabolic acidosis stimulates K⁺ efflux from cells in exchange for H⁺ influx.