An evaluation of the low-pH enzymatic assay of urinary d-glucaric acid, and its use as a marker of enzyme induction in exocrine pancreatic disease

Abstract

We have evaluated a low-pH enzymatic method for measuring urinary d-glucaric acid, and its usefulness as a marker of ‘enzyme induction’ in patients with exocrine pancreatic disease. The coefficient of variation lay between 7.5 and 10.9% for within-batch precision, and between 7.9 and 19.8% for between-batch precision. The useful range of the method was 20–200 μmol/l, with a lower detection limit of 11 μmol/l. The molar concentration ratio of d-glucaric acid to creatinine in urine correlated with the 8-h output of d-glucaric acid ( p < 0.005): both indices were significantly higher in a group of 29 patients with exocrine pancreatic disease than in controls (median ratios 4.6 and 2.9 × 10 −3, p < 0.005; median outputs 14.0 and 8.8 μmol/8 h, respectively, p < 0.005). Comparison with the results of theophylline tests in the same group of patients showed that whereas 72% of patients had theophylline clearances higher than the highest value in controls, 45% of the group had increased d-glucaric acid/creatinine ratios, whilst only 21% had increased outputs of d-glucaric acid. Paradoxically, in patients with established liver disease in whom drug metabolism was impaired urinary d-glucaric acid values were amongst the highest encountered in the study. Thus, the obvious advantages of the method — non-invasive, simple, reproducible, inexpensive, easily applied to out-patients — are offset by an unacceptably low predictive value as an indicator of microsomal ‘enzyme induction’.