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

Abstract

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.

Keywords: Hippurate; Metabolic acidosis; Serum and urine anion gap; Toluene; Urine osmolal gap.

Fig. 1

Formulae to calculate AG, UAG, and UOG. (A) The relationship between the other UC and UA is given by the following equation: [Na⁺] + [K⁺] + [UC] = [Cl⁻] + [HCO₃⁻] + [UA]. In other words, we transform the equation as follows and use the difference between UA and UC as the anion gap: [Na⁺] + [K⁺] − [Cl⁻] − [HCO₃⁻] = [UA]–[UC] = AG. This means that the sum of the cations in the body ([Na⁺], [K⁺], and other cations) is equal to the sum of the anions ([Cl⁻], [HCO₃⁻], and other anions). The normally measured cations ([Na⁺] and [K⁺]) and anions ([Cl⁻] and [HCO₃⁻]) make up the majority of each ion. Since [K⁺] is much lower than [Na⁺] in the blood, it may be omitted from the equation [1]. (B) Na⁺, K⁺, and Cl⁻ excreted in urine are derived from the diet. Since Na⁺ and K⁺ are usually absorbed from the gastrointestinal tract more than Cl⁻, urine AG is approximately 20–90 mmol/L [2]. (C) The calculated urine osmolality derived by the following equation: 2 × (urine [Na⁺] + urine [K⁺]) + urine [urea nitrogen] (mg/dL)/2.8 + urine [glucose] (mg/dL)/18 = Urine osmolality [2, 3]. In most cases, especially in normal plasma glucose concentration, urinary glucose excretion is 0. Thus, urine osmolality was calculated by the following equation: 2 × (urine [Na⁺] + urine [K⁺]) + urine [urea nitrogen] (mg/dL)/2.8. AG anion gap, UAG urine anion gap, UOG urine osmolal gap, [Na⁺] sodium concentration, [K⁺] potassium concentration, [Cl⁻] chloride concentration, [HCO₃⁻] bicarbonate concentration, UC unmeasured cations, UA unmeasured anions