What are the causes of non-anion gap acidosis (NAGA)?

From the Guidelines

Non-anion gap acidosis (NAGA) is primarily caused by the loss of bicarbonate or an increase in chloride ions.

Causes of NAGA

• Gastrointestinal loss of bicarbonate: This can occur due to severe diarrhea or the use of certain medications that cause bicarbonate loss in the gut.
• Renal tubular acidosis: A condition where the kidneys are unable to properly acidify the urine, leading to a loss of bicarbonate and an increase in chloride ions 1.
• Excessive saline administration: The use of excessive saline for fluid and electrolyte replacement can lead to hyperchloremia, which can cause NAGA, as seen in patients recovering from diabetic ketoacidosis (DKA) 1.
• Dietary factors: A diet high in animal protein and low in fruits and vegetables can lead to an imbalance between nonvolatile acids and alkali, resulting in a chronic low-grade metabolic acidosis, which can worsen with age as kidney function declines 1.

Key Points

• NAGA can be transient and not clinically significant in some cases, but it can also be a sign of underlying kidney disease or other serious conditions.
• The treatment of NAGA depends on the underlying cause, but it may involve the use of sodium bicarbonate supplementation or an increase in fruit and vegetable intake to help buffer nonvolatile acids 1.
• Regular monitoring of serum bicarbonate levels is important in patients with chronic renal failure or those undergoing dialysis to prevent acidemia and its associated complications 1.

From the Research

Causes of Non-Anion Gap Acidosis (NAGA)

The causes of NAGA can be attributed to several factors, including:

• Loss of base, as seen in cases of high-volume ileostomy output causing large bicarbonate losses 2
• Decreased renal excretion of acid 3
• Increased acid production is not typically associated with NAGA, but rather with high anion gap metabolic acidosis 3
• Administration of large quantities of chloride-containing solutions in the treatment of hypovolemia and various shock states, leading to hyperchloremic acidosis 4
• Renal tubular acidosis (RTA), a subset of non-anion gap metabolic acidoses that result from complex disturbances in renal acid excretion 5
• Ileal neobladder urinary diversion for the treatment of bladder cancer, which can lead to a non-anion gap metabolic acidosis due to a urinary tract infection and ureteroenterostomy 6
• Diarrhea, which can cause loss of large quantities of base and result in non-anion gap metabolic acidosis 4

Mechanisms Leading to NAGA

The mechanisms leading to NAGA include:

• Loss of bicarbonate-rich fluids, such as in cases of diarrhea or ileostomy output 2, 4
• Inability of the kidneys to excrete acid, as seen in renal tubular acidosis 5
• Increased chloride load, as seen in cases of administration of large quantities of chloride-containing solutions 4