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Abstract: SA-PO511

Treatment of 5-oxyproline Anion Gap Acidosis with N-acetylcysteine

Session Information

Category: Fluid, Electrolytes, and Acid-Base Disorders

  • 1102 Fluid, Electrolyte, and Acid-Base Disorders: Clinical

Authors

  • Fields, Ryan, Emory University, Atlanta, Georgia, United States
  • Franch, Harold A., Emory University, Atlanta, Georgia, United States
Introduction

Over 60 million Americans use acetaminophen (APAP) weekly. Mitochondrial APAP metabolism requires the consumption of glutathione which is produced by the glutathione cycle (GC) consuming the amino acid, cystine. 5-oxoproline anion gap (AG) metabolic acidosis occurs when high dose APAP therapy combined with inadequate protein intake leads to depletion of cystine. Low cystine levels block the GC causing accumulation of 5 oxyproline. N-Acetylcysteine, used to threat APAP overdose, restores the GC and should reduce 5-oxoproline production.

Case Description

81 y.o. woman with past Roux-n-Y gastric bypass, leukemia s/p bone marrow transplant, cervical vertebral collapse s/p surgeries was admitted for cervical and abdominal pain and anorexia and found to have UTI and severe constipation. Her pain does not respond to narcotics: she took APAP 650 BID and 2 tablets of Fioricet (APAP 600 mg) q 8 hours at home. She received IV APAP 1000 mg BID and 2 Fioricet BID in hospital. Her baseline normal gap metabolic acidosis is treated with Ca citrate, but on admission patient had mixed non-gap and AG metabolic acidosis with normal ketones, lactate, eGFR. Urine electrolytes showed sodium 35 mEq/L but chloride was undetectable, suggesting anion drag. On Day 2 riifaxamin was started for presumed bacterial overgrowth AG acidosis. She refused to stop APAP, but reduced to ~ 2200 mg daily and N acetyl cysteine 35 mg/kg BID stared day 5. AG normalized day 8. Samples obtained day 2 showed serum d-lactate normal and urine organic a 5-oxoproline was 44-fold top of normal range with no other organic acid elevated more than 6-fold (lactate 4-fold).

Discussion

Clinical recognition of 5-oxoproline metabolic acidosis is important given delays in urinary organic acid results. Treatment is discontinuing APAP and feeding protein. This first report of N-acetylcysteine treatment may provide an option if APAP cannt be discontinued when adequate protein intake is not possible.