An educational case of toluene intoxication: importance of kidney function and timing in diagnosis

Metabolic acidosis (MA) is common in daily clinical settings and requires evaluation not only by serum anion gap (AG) but also by urine AG (UAG) and urine osmolal gap (UOG) to investigate potential causes and determine appropriate treatment. Herein, we report an educational case of non-gap (normal AG) MA (pH 7.16, HCO₃^- 8.4, AG 11.6) with nausea and fatigue. The patient had three episodes of hospital admission with MA in the previous three months. Although serum lactate and ketone levels were negative, the AG levels were notably inconsistent (elevated or not) each time. Nevertheless, the patient was suspected to have toluene intoxication because of low UAG and high UOG levels in the non-gap acidosis phase. Eventually, he was diagnosed with toluene intoxication due to a significantly elevated urinary hippurate level (28.7 g/L) despite never admitting to using toluene. Additionally, he had a high AG only in the presence of significant kidney dysfunction, which suggests that the high AG was either due to kidney dysfunction or accumulated hippurate in the blood (when UOG was high). Thus, it should be noted that the use of serum AG alone may lead to incorrect determination of cause(s) of MA when kidney dysfunction coexists, and that UAG and UOG, in addition to AG, are necessary to determine correct diagnosis.