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Abstract: PO1169

Pyroglutamic Acidosis: Gaps in the Gaps

Session Information

Category: Fluid, Electrolyte, and Acid-Base Disorders

  • 902 Fluid, Electrolyte, and Acid-Base Disorders: Clinical


  • Rajan, Roy, Dartmouth-Hitchcock Health GraniteOne, Lebanon, New Hampshire, United States
  • Sedlacek, Martin, Dartmouth-Hitchcock Health GraniteOne, Lebanon, New Hampshire, United States

Prolonged use of acetaminophen can lead to an acquired form of pyroglutamic acidosis, a form of anion gap metabolic acidosis (AGMA) from increased production of 5- Oxoproline (pyroglutamic acid). 5- Oxyproline accumulates in the body due to the failure its breakdown by 5- Oxoprolinase and is excreted in urine causing positive urine anion gap (AG).

Case Description

Case 1:
First patient is a 59 y/o man with normal prior renal function with baseline creatinine (Cr) of 0.7mg/dl, admitted with severe pancreatitis. At the time of presentation his serum calcium level 15mg/dL (8.5-10.5) and his serum Cr level was 2.21 mg/dl. His hospital course was complicated by sepsis due to multiple intra-abdominal infections and required iv pressor and ventilator support. He was later started on continuous veno-venous hemofiltration (CVVH) temporarily with recovery of renal function. Acetaminophen 1 gram three times daily was administered for pain control. On the 65th day of hospitalization, his bicarb was 15 with an AG of 14, but when corrected for low albumin of 1.8, it increased to 20. HE had a positive urine AG and his urine 5-Oxyroline was 1583 mmol/mol Cr (range < 62).

Case 2:
Second patient is a 74-year-old man with a history of stage 4 CKD admitted with sepsis due to perforated viscus. He had long hospital course due to ischemic gut with continued bleeding and sepsis due to perforation. He was on Acetaminophen 1 gram four times daily for pain control. His serum bicarbonate started trending down to a nadir of 11 mmol/L on the 43rd day of admission. He had an anion gap of 12, but corrected anion gap was 18 and had a positive urine AG. His urine 5- oxyproline was 6361 mmol/mol creatinine (range <62).


Both patients in our case series had critical illness, were malnourished, and was recovering from prolonged infection and sepsis which are risk factors for pyroglutamic acidosis and low serum albumin levels. Their AG might appear to be within normal range if not corrected for albumin. Urine anion gap is an indirect method of measuring urine ammonia excretion and is elevated in renal tubular acidosis and from excretion of organic anions like 5-Oxyproline and ketone bodies. Correction for AG is proposed as measured AG + 2.5× (“normal” albumin ~4.2 − measured albumin [g/dl]). This uncorrected “normal AGMA” with a positive urine AG due to pyroglutamic acidosis can mimic renal tubular acidosis and can be easily missed.