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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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.

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 mumol/l, with a lower detection limit of 11 mumol/l. The molar concentration ratio of D-glucaric acid to creatinine in urine correlated with the 8-h output of D-glucaric acid (p less than 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 X 10(-3), p less than 0.005; median outputs 14.0 and 8.8 mumol/8 h, respectively, p less than 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'.[1]


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