A previously undescribed side effect of icodextrin: Overestimation of glycemia by glucose analyzer

Objective: Serious discrepancies between glycemia measurements obtained wit h an Accutrend Sensor (Boehringer Mannheim GmbH, Mannheim, Germany) type an alyzer (based on a glucose dehydrogenase enzymatic reaction) and measuremen ts obtained in the laboratory by a reference method (hexokinase) have been found in an insulin-requiring, diabetic, continuous ambulatory peritoneal d ialysis (CAPD) patient treated with icodextrin 7.5% (Extraneal; Baxter Heal thcare SA, Castlebar, Ireland), a new osmotic agent for peritoneal dialysis . We therefore investigated the respective role of the Analyzer and of the glucose polymer in this hitherto undescribed problem. Design: Glycemia was measured simultaneously on venous blood using a refere nce laboratory technique, and on capillary blood using the Accutrend Sensor glucose analyzer in three groups of CAPD patients: 6 patients on Extraneal for at least 1 week, 6 patients receiving their first Extraneal exchange, and 8 patients never exposed to Extraneal. In the first group of patients, glycemia was also measured with another analyzer (Glucocard; Menarini Diagn ostics, Firenze, Italy) using a different enzymatic reaction (glucose oxida se). In a separate study, whole blood of a normal subject was spiked with c oncentrated solutions of glucose and icodextrin and some of its metabolites (maltose, maltotriose, maltopentaose). Once again, comparative measurement s of glycemia were performed with the Accutrend Sensor, with two other kits using a glucose dehydrogenase enzyme reaction, and with the hexokinase ref erence method. Results: In 6 CAPD patients treated with once-daily exchanges with Extranea l for a minimum of 7 consecutive days, we confirmed overestimation of glyce mia by the Accutrend Sensor of 65 +/- 26 mg/dL compared to reference values (p < 0.01), and of 69 +/- 25 mg/dL(p < 0.001) compared to measurements obt ained with the Glucocard monitor. In 6 other CAPD patients studied at the e nd of one single icodextrin exchange, overestimation of 61 +/- 11 mg/dL was already present (p < 0.001). On the other hand, in 8 CAPD patients never t reated with icodextrin, there was no discrepancy between the Accutrend Sens or readings and reference values. The measurements in spiked blood confirme d that only the Accutrend Sensor overestimates glycemia in the presence of maltose and glucose polymers. The overestimation decreased as the molecular size of the saccharides added to blood increased. There was no overestimat ion when other kits using a dehydrogenase enzyme were tested. Conclusion: The overestimation observed is probably related to the presence of oligosaccharides (mainly maltose), derivatives of glucose polymers pres ent in Extraneal and absorbed via the peritoneal route, in the blood of pat ients treated with icodextrin. The glucose dehydrogenase characterizing the Accutrend Sensor, an enzyme of the pyrroloquinolinequinone class, very lik ely reacts with the free reducing group of the glucose molecule located at the end of each saccharide chain. This would not be the case for the Glucoc ard monitor using glucose oxidase, for other kits using glucose dehydrogena se, and for the reference method based on hexokinase. The Accutrend Sensor type of analyzers are therefore not suitable for regular monitoring of glyc emia in diabetic PD patients treated with icodextrin.