Urine anion gap: telling diarrhea from RTA

Normal anion gap acidosis: gut or kidney?

Two patients have the same blood results: bicarbonate 14 mEq/L, chloride high and a normal anion gap. One has diarrhea. The other has a kidney that can't get rid of acid. The blood can't tell them apart, but the urine can. The urine anion gap is the tool that tells gut from kidney in a normal gap acidosis.

When the body loses bicarbonate, chloride rises to take its place, so the gap stays normal. That is a normal anion gap, or high-chloride, hyperchloremic metabolic acidosis.^[1][11]

It has two big sources. The gut loses bicarbonate, with diarrhea or a fistula, or the kidney fails to handle acid, as in renal tubular acidosis (RTA).^[1][4]

Ammonium: how the kidney gets rid of acid

The kidney gets rid of acid mainly as ammonium (NH₄⁺). For every ammonium it excretes, it adds one new bicarbonate to the blood. In acidosis, a healthy kidney can raise its ammonium excretion several-fold.^[4][5]

That link is why ammonium matters here. A kidney that responds to acidosis by excreting more ammonium is also making new bicarbonate. If the acidosis persists while ammonium output is high, the bicarbonate is usually being lost somewhere else, most often the gut.^[4][6]

So the key question in a normal gap acidosis is: is this kidney pumping out ammonium?

• Yes: the kidney is responding, so the bicarbonate was lost elsewhere, usually the gut.^[4][6]
• No: the kidney is the problem.^[4][6]

There is a catch: urine ammonium isn't part of a routine urine test. So it is estimated.^[9]

The urine anion gap formula

Urine, like blood, is electrically neutral. The lab measures sodium and potassium, the positive ions, and chloride, the negative one. Ammonium is a positive ion the lab doesn't measure, and it leaves mostly with chloride.^[4][12]

More ammonium means more chloride, which outweighs sodium plus potassium, so the gap turns negative. With good ammonium excretion, it is typically about −20 to −50 mEq/L.^[4][12]

Worked examples: urine anion gap in diarrhea vs RTA

Same blood, opposite urine. Patient 1's gap of −40 sits inside the −20 to −50 range of good ammonium excretion; patient 2's is positive. In both cases the urine sodium is above 25 mEq/L, so the gap can be read (see the limits below).^[4][12]

Urine pH: why it can mislead

In distal RTA, the distal tubule can't secrete enough acid, so urine pH stays above 5.5.^[3]

But with diarrhea and low potassium, so much ammonia buffers the urine that its pH can rise above 5.5 too. A high urine pH alone does not prove the kidney is failing to excrete ammonium.^[4][5]

Two limits: when the gap misleads

1. Unmeasured urinary anions. Ketoacids, or hippurate from toluene, carry ammonium out without chloride, so the gap can look positive even when the kidney works.^[4][8]
2. A very dry patient. With a urine sodium below about 25 mEq/L, low distal sodium delivery blunts acid excretion, so a positive gap can mislead.^[4][10]

And the urine anion gap tracks measured ammonium only loosely, so it is an estimate, not a measurement.^[8][9]

Putting it together, step by step

1. Confirm a normal serum anion gapNa⁺ − (Cl⁻ + HCO₃⁻) is normal, so this is a hyperchloremic metabolic acidosis.^[1]
2. Check the gap can be readUrine sodium above about 25 mEq/L and no ketoacids or hippurate in the urine.^[4]
3. Calculate the urine anion gap(urine Na⁺ + urine K⁺) − urine Cl⁻.^[12]
4. Read the signNegative: the kidney is excreting ammonium, so the gut usually lost the bicarbonate. Zero or positive: the kidney is failing to excrete acid, as in distal RTA.^[6]
5. Don't let the urine pH overrule itA urine pH above 5.5 can occur with diarrhea and low potassium.^[4]