The urine anion gap result is interpreted in the context of a patient who has a non-anion gap metabolic acidosis (NAGMA), characterized by low serum bicarbonate with a normal serum anion gap. A negative urine anion gap (typically -20 to -50 mEq/L) indicates that the kidneys are appropriately excreting ammonium (NH4+) in response to the acidosis. Since NH4+ is excreted with chloride, high ammonium excretion raises urine chloride relative to sodium plus potassium, pulling the gap negative. This pattern points to an extrarenal cause of the acidosis, most commonly diarrhea or other gastrointestinal bicarbonate losses.

A positive urine anion gap (greater than 0 mEq/L) in the setting of NAGMA indicates that the kidneys are failing to appropriately increase ammonium excretion. This points to a renal tubular acidosis (RTA). Type 1 (distal) RTA is characterized by impaired hydrogen ion secretion in the distal tubule, resulting in a urine pH typically above 5.5 and hypokalemia. Type 4 (hyperkalemic) RTA results from aldosterone deficiency or resistance and presents with hyperkalemia and a urine pH below 5.5.

A urine anion gap near zero is indeterminate and may require additional testing, such as the urine osmolar gap, which is a more direct estimate of urinary ammonium and can be helpful when the UAG result is equivocal.

Use the urine anion gap as part of the diagnostic workup for non-anion gap metabolic acidosis. After confirming NAGMA (low bicarbonate, normal serum anion gap, and hyperchloremia), the key clinical question is whether the acidosis is due to renal or extrarenal causes. The urine anion gap answers this question by indirectly estimating whether the kidneys are appropriately excreting ammonium.

The most common clinical scenarios include: distinguishing diarrhea-induced bicarbonate loss (negative UAG) from renal tubular acidosis (positive UAG); evaluating unexplained hyperchloremic metabolic acidosis in hospitalized patients; and working up possible Type 1 or Type 4 RTA in patients with persistent metabolic acidosis of unclear etiology. It is a simple, inexpensive test that requires only a spot urine sample for sodium, potassium, and chloride.

The urine anion gap is only valid in the setting of non-anion gap metabolic acidosis. It should not be used when the serum anion gap is elevated, as the filtered unmeasured anions in the urine can confound the calculation. It is also unreliable in patients with significant ketonuria or other organic anions in the urine (e.g., hippurate from toluene exposure), as these anions are excreted with sodium rather than ammonium and can falsely elevate the UAG.

The test assumes that the major unmeasured cation in urine is ammonium. In patients with very low urine sodium (such as those who are volume-depleted), the UAG may be unreliable because low sodium delivery to the collecting duct limits the ability to interpret the gap. In these cases, the urine osmolar gap may be a better alternative for estimating urinary ammonium.

Polyuria and very dilute urine can also affect results. Additionally, certain medications such as lithium (an unmeasured cation in urine) can interfere with the calculation. The UAG provides a qualitative assessment of ammonium excretion and should always be interpreted alongside the clinical picture, serum potassium, urine pH, and other laboratory findings.