Icodextrin in Peritoneal Dialysis: Early Development and Clinical Use

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Abstract
Over the past decade we have explored the potential of a starch-derived glucose polymer (icodextrin) as a “colloid” osmotic agent and clinically adapted it to produce sustained ultrafiltration over long dwell exchanges. An optimal osmotic profile was defined using a series of glucose polymer formulations of varying molecular distribution. Initially, a readily available dextrin formulation (Caloreen) with a bimodal molecular weight profile was used. Five and 10% solutions containing this formulation [weight average MW (Mw) of 7000 dalton and number average MW (Mn) of 960 dalton were nearly twice as effective as 1.36% and 3.86% glucose solutions, but their effectiveness was limited by rapid absorption of fractions less than 12 glucose units. Further modification isolated a purified “high” MW fraction containing chain length greater than 12 glucose units with Mw of 16 823 dalton and Mn of 5304 dalton. A 5% solution containing this fraction, iso-osmolar to uremic plasma, provided calorie load half that of a 1.36% glucose, yet produced increased and sustained ultrafiltration for up to 12 hours by a mechanism resembling “colloid” osmosis. Only a fraction of glucose polymer load was absorbed via the lymphatic pathway, but its metabolism was incomplete, resulting in the accumulation of maltose. Although it was devoid of any detectable adverse effect in the short term, long-term concerns remained. In studies using a single daily overnight exchange of glucose polymer combined with three daytime exchanges of glucose over 5 days, 10 days, and 3 months, we have shown that a constant peritoneal clearance (3 mL/minute) ensures a steady-state level of maltose in the serum within 10 days, and this remains stable for up to 3 months without any adverse effects. The relative inertness of icodextrin has been the key factor in its success as the first “colloid” osmotic agent in clinical use. It is safe and effective, and the demonstration of steady-state levels of accumulated maltose and oligosaccharides without any adverse effects has been encouraging and provided further impetus to proceed with longer-term studies.